WorldWideScience

Sample records for specific false discovery

  1. Specificity control for read alignments using an artificial reference genome-guided false discovery rate.

    Science.gov (United States)

    Giese, Sven H; Zickmann, Franziska; Renard, Bernhard Y

    2014-01-01

    Accurate estimation, comparison and evaluation of read mapping error rates is a crucial step in the processing of next-generation sequencing data, as further analysis steps and interpretation assume the correctness of the mapping results. Current approaches are either focused on sensitivity estimation and thereby disregard specificity or are based on read simulations. Although continuously improving, read simulations are still prone to introduce a bias into the mapping error quantitation and cannot capture all characteristics of an individual dataset. We introduce ARDEN (artificial reference driven estimation of false positives in next-generation sequencing data), a novel benchmark method that estimates error rates of read mappers based on real experimental reads, using an additionally generated artificial reference genome. It allows a dataset-specific computation of error rates and the construction of a receiver operating characteristic curve. Thereby, it can be used for optimization of parameters for read mappers, selection of read mappers for a specific problem or for filtering alignments based on quality estimation. The use of ARDEN is demonstrated in a general read mapper comparison, a parameter optimization for one read mapper and an application example in single-nucleotide polymorphism discovery with a significant reduction in the number of false positive identifications. The ARDEN source code is freely available at http://sourceforge.net/projects/arden/.

  2. A constrained polynomial regression procedure for estimating the local False Discovery Rate

    Directory of Open Access Journals (Sweden)

    Broët Philippe

    2007-06-01

    Full Text Available Abstract Background In the context of genomic association studies, for which a large number of statistical tests are performed simultaneously, the local False Discovery Rate (lFDR, which quantifies the evidence of a specific gene association with a clinical or biological variable of interest, is a relevant criterion for taking into account the multiple testing problem. The lFDR not only allows an inference to be made for each gene through its specific value, but also an estimate of Benjamini-Hochberg's False Discovery Rate (FDR for subsets of genes. Results In the framework of estimating procedures without any distributional assumption under the alternative hypothesis, a new and efficient procedure for estimating the lFDR is described. The results of a simulation study indicated good performances for the proposed estimator in comparison to four published ones. The five different procedures were applied to real datasets. Conclusion A novel and efficient procedure for estimating lFDR was developed and evaluated.

  3. Sample Size Calculation for Controlling False Discovery Proportion

    Directory of Open Access Journals (Sweden)

    Shulian Shang

    2012-01-01

    Full Text Available The false discovery proportion (FDP, the proportion of incorrect rejections among all rejections, is a direct measure of abundance of false positive findings in multiple testing. Many methods have been proposed to control FDP, but they are too conservative to be useful for power analysis. Study designs for controlling the mean of FDP, which is false discovery rate, have been commonly used. However, there has been little attempt to design study with direct FDP control to achieve certain level of efficiency. We provide a sample size calculation method using the variance formula of the FDP under weak-dependence assumptions to achieve the desired overall power. The relationship between design parameters and sample size is explored. The adequacy of the procedure is assessed by simulation. We illustrate the method using estimated correlations from a prostate cancer dataset.

  4. Estimation of the false discovery proportion with unknown dependence.

    Science.gov (United States)

    Fan, Jianqing; Han, Xu

    2017-09-01

    Large-scale multiple testing with correlated test statistics arises frequently in many scientific research. Incorporating correlation information in approximating false discovery proportion has attracted increasing attention in recent years. When the covariance matrix of test statistics is known, Fan, Han & Gu (2012) provided an accurate approximation of False Discovery Proportion (FDP) under arbitrary dependence structure and some sparsity assumption. However, the covariance matrix is often unknown in many applications and such dependence information has to be estimated before approximating FDP. The estimation accuracy can greatly affect FDP approximation. In the current paper, we aim to theoretically study the impact of unknown dependence on the testing procedure and establish a general framework such that FDP can be well approximated. The impacts of unknown dependence on approximating FDP are in the following two major aspects: through estimating eigenvalues/eigenvectors and through estimating marginal variances. To address the challenges in these two aspects, we firstly develop general requirements on estimates of eigenvalues and eigenvectors for a good approximation of FDP. We then give conditions on the structures of covariance matrices that satisfy such requirements. Such dependence structures include banded/sparse covariance matrices and (conditional) sparse precision matrices. Within this framework, we also consider a special example to illustrate our method where data are sampled from an approximate factor model, which encompasses most practical situations. We provide a good approximation of FDP via exploiting this specific dependence structure. The results are further generalized to the situation where the multivariate normality assumption is relaxed. Our results are demonstrated by simulation studies and some real data applications.

  5. 28 CFR 2.30 - False information or new criminal conduct: Discovery after release.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false False information or new criminal conduct... Prisoners and Parolees § 2.30 False information or new criminal conduct: Discovery after release. If... willfully provided false information or misrepresented information deemed significant to his application for...

  6. Controlling the Rate of GWAS False Discoveries.

    Science.gov (United States)

    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.

  7. Controlling the local false discovery rate in the adaptive Lasso

    KAUST Repository

    Sampson, J. N.

    2013-04-09

    The Lasso shrinkage procedure achieved its popularity, in part, by its tendency to shrink estimated coefficients to zero, and its ability to serve as a variable selection procedure. Using data-adaptive weights, the adaptive Lasso modified the original procedure to increase the penalty terms for those variables estimated to be less important by ordinary least squares. Although this modified procedure attained the oracle properties, the resulting models tend to include a large number of "false positives" in practice. Here, we adapt the concept of local false discovery rates (lFDRs) so that it applies to the sequence, λn, of smoothing parameters for the adaptive Lasso. We define the lFDR for a given λn to be the probability that the variable added to the model by decreasing λn to λn-δ is not associated with the outcome, where δ is a small value. We derive the relationship between the lFDR and λn, show lFDR =1 for traditional smoothing parameters, and show how to select λn so as to achieve a desired lFDR. We compare the smoothing parameters chosen to achieve a specified lFDR and those chosen to achieve the oracle properties, as well as their resulting estimates for model coefficients, with both simulation and an example from a genetic study of prostate specific antigen.

  8. Testing jumps via false discovery rate control.

    Science.gov (United States)

    Yen, Yu-Min

    2013-01-01

    Many recently developed nonparametric jump tests can be viewed as multiple hypothesis testing problems. For such multiple hypothesis tests, it is well known that controlling type I error often makes a large proportion of erroneous rejections, and such situation becomes even worse when the jump occurrence is a rare event. To obtain more reliable results, we aim to control the false discovery rate (FDR), an efficient compound error measure for erroneous rejections in multiple testing problems. We perform the test via the Barndorff-Nielsen and Shephard (BNS) test statistic, and control the FDR with the Benjamini and Hochberg (BH) procedure. We provide asymptotic results for the FDR control. From simulations, we examine relevant theoretical results and demonstrate the advantages of controlling the FDR. The hybrid approach is then applied to empirical analysis on two benchmark stock indices with high frequency data.

  9. Testing jumps via false discovery rate control.

    Directory of Open Access Journals (Sweden)

    Yu-Min Yen

    Full Text Available Many recently developed nonparametric jump tests can be viewed as multiple hypothesis testing problems. For such multiple hypothesis tests, it is well known that controlling type I error often makes a large proportion of erroneous rejections, and such situation becomes even worse when the jump occurrence is a rare event. To obtain more reliable results, we aim to control the false discovery rate (FDR, an efficient compound error measure for erroneous rejections in multiple testing problems. We perform the test via the Barndorff-Nielsen and Shephard (BNS test statistic, and control the FDR with the Benjamini and Hochberg (BH procedure. We provide asymptotic results for the FDR control. From simulations, we examine relevant theoretical results and demonstrate the advantages of controlling the FDR. The hybrid approach is then applied to empirical analysis on two benchmark stock indices with high frequency data.

  10. Characterization and correction of the false-discovery rates in resting state connectivity using functional near-infrared spectroscopy

    Science.gov (United States)

    Santosa, Hendrik; Aarabi, Ardalan; Perlman, Susan B.; Huppert, Theodore J.

    2017-05-01

    Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique that uses low levels of red to near-infrared light to measure changes in cerebral blood oxygenation. Spontaneous (resting state) functional connectivity (sFC) has become a critical tool for cognitive neuroscience for understanding task-independent neural networks, revealing pertinent details differentiating healthy from disordered brain function, and discovering fluctuations in the synchronization of interacting individuals during hyperscanning paradigms. Two of the main challenges to sFC-NIRS analysis are (i) the slow temporal structure of both systemic physiology and the response of blood vessels, which introduces false spurious correlations, and (ii) motion-related artifacts that result from movement of the fNIRS sensors on the participants' head and can introduce non-normal and heavy-tailed noise structures. In this work, we systematically examine the false-discovery rates of several time- and frequency-domain metrics of functional connectivity for characterizing sFC-NIRS. Specifically, we detail the modifications to the statistical models of these methods needed to avoid high levels of false-discovery related to these two sources of noise in fNIRS. We compare these analysis procedures using both simulated and experimental resting-state fNIRS data. Our proposed robust correlation method has better performance in terms of being more reliable to the noise outliers due to the motion artifacts.

  11. Use of the false discovery rate for evaluating clinical safety data.

    Science.gov (United States)

    Mehrotra, Devan V; Heyse, Joseph F

    2004-06-01

    Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed 'Double FDR' approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term 'Double FDR'.

  12. Challenges of the information age: the impact of false discovery on pathway identification.

    Science.gov (United States)

    Rog, Colin J; Chekuri, Srinivasa C; Edgerton, Mary E

    2012-11-21

    Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored. The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured. A PubMed search enumerated cancer-related literature published for any gene in the networks. Using three, two, and one maximum intervening step between input genes to populate the network, networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225 cancer-related articles per network gene. This can be attributed to the richly populated pathways databases and the interest in the molecular basis of cancer. As information sources become enriched, they are more likely to generate plausible mechanisms for false discoveries.

  13. Sample size reassessment for a two-stage design controlling the false discovery rate.

    Science.gov (United States)

    Zehetmayer, Sonja; Graf, Alexandra C; Posch, Martin

    2015-11-01

    Sample size calculations for gene expression microarray and NGS-RNA-Seq experiments are challenging because the overall power depends on unknown quantities as the proportion of true null hypotheses and the distribution of the effect sizes under the alternative. We propose a two-stage design with an adaptive interim analysis where these quantities are estimated from the interim data. The second stage sample size is chosen based on these estimates to achieve a specific overall power. The proposed procedure controls the power in all considered scenarios except for very low first stage sample sizes. The false discovery rate (FDR) is controlled despite of the data dependent choice of sample size. The two-stage design can be a useful tool to determine the sample size of high-dimensional studies if in the planning phase there is high uncertainty regarding the expected effect sizes and variability.

  14. Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate

    DEFF Research Database (Denmark)

    Andreassen, Ole A; Thompson, Wesley K; Schork, Andrew J

    2013-01-01

    are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability...... associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders....

  15. False-Positive Rate Determination of Protein Target Discovery using a Covalent Modification- and Mass Spectrometry-Based Proteomics Platform

    Science.gov (United States)

    Strickland, Erin C.; Geer, M. Ariel; Hong, Jiyong; Fitzgerald, Michael C.

    2014-01-01

    Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in complex biological mixtures. Knowing the false-positive rate of protein target discovery in proteome-wide SPROX experiments is important for the correct interpretation of results. Reported here are the results of a control SPROX experiment in which chemical denaturation data is obtained on the proteins in two samples that originated from the same yeast lysate, as would be done in a typical SPROX experiment except that one sample would be spiked with the test ligand. False-positive rates of 1.2-2.2 % and analysis of the isobaric mass tag (e.g., iTRAQ®) reporter ions used for peptide quantitation. Our results also suggest that technical replicates can be used to effectively eliminate such false positives that result from this random error, as is demonstrated in a SPROX experiment to identify yeast protein targets of the drug, manassantin A. The impact of ion purity in the tandem mass spectral analyses and of background oxidation on the false-positive rate of protein target discovery using SPROX is also discussed.

  16. Individual differences in susceptibility to false memories: The effect of memory specificity.

    Science.gov (United States)

    Dewhurst, Stephen A; Anderson, Rachel J; Berry, Donna M; Garner, Sarah R

    2017-06-25

    Previous research has highlighted the wide individual variability in susceptibility to the false memories produced by the Deese/Roediger-McDermott (DRM) procedure [Deese, J. (1959). On the prediction of occurrence of particular verbal intrusions in immediate recall. Journal of Experimental Psychology, 58, 17-22; Roediger, H. L., III, & McDermott, K. B. (1995). Creating false memories: Remembering words not presented in lists. Journal of Experimental Psychology: Learning, Memory, & Cognition, 21, 803-814]. The current study investigated whether susceptibility to false memories is influenced by individual differences in the specificity of autobiographical memory retrieval. Memory specificity was measured using the Sentence Completion for Events from the Past Test (SCEPT) [Raes, F., Hermans, D., Williams, J. M. G., & Eelen, P. (2007). A sentence completion procedure as an alternative to the Autobiographical Memory Test for assessing overgeneral memory in non-clinical populations. Memory, 15, 495-507]. Memory specificity did not correlate with correct recognition, but a specific retrieval style was positively correlated with levels of false recognition. It is proposed that the contextual details that frequently accompany false memories of nonstudied lures are more accessible in individuals with specific retrieval styles.

  17. A comparative review of estimates of the proportion unchanged genes and the false discovery rate

    Directory of Open Access Journals (Sweden)

    Broberg Per

    2005-08-01

    Full Text Available Abstract Background In the analysis of microarray data one generally produces a vector of p-values that for each gene give the likelihood of obtaining equally strong evidence of change by pure chance. The distribution of these p-values is a mixture of two components corresponding to the changed genes and the unchanged ones. The focus of this article is how to estimate the proportion unchanged and the false discovery rate (FDR and how to make inferences based on these concepts. Six published methods for estimating the proportion unchanged genes are reviewed, two alternatives are presented, and all are tested on both simulated and real data. All estimates but one make do without any parametric assumptions concerning the distributions of the p-values. Furthermore, the estimation and use of the FDR and the closely related q-value is illustrated with examples. Five published estimates of the FDR and one new are presented and tested. Implementations in R code are available. Results A simulation model based on the distribution of real microarray data plus two real data sets were used to assess the methods. The proposed alternative methods for estimating the proportion unchanged fared very well, and gave evidence of low bias and very low variance. Different methods perform well depending upon whether there are few or many regulated genes. Furthermore, the methods for estimating FDR showed a varying performance, and were sometimes misleading. The new method had a very low error. Conclusion The concept of the q-value or false discovery rate is useful in practical research, despite some theoretical and practical shortcomings. However, it seems possible to challenge the performance of the published methods, and there is likely scope for further developing the estimates of the FDR. The new methods provide the scientist with more options to choose a suitable method for any particular experiment. The article advocates the use of the conjoint information

  18. Insect-Specific Virus Discovery: Significance for the Arbovirus Community

    Directory of Open Access Journals (Sweden)

    Bethany G. Bolling

    2015-09-01

    Full Text Available Arthropod-borne viruses (arboviruses, especially those transmitted by mosquitoes, are a significant cause of morbidity and mortality in humans and animals worldwide. Recent discoveries indicate that mosquitoes are naturally infected with a wide range of other viruses, many within taxa occupied by arboviruses that are considered insect-specific. Over the past ten years there has been a dramatic increase in the literature describing novel insect-specific virus detection in mosquitoes, which has provided new insights about viral diversity and evolution, including that of arboviruses. It has also raised questions about what effects the mosquito virome has on arbovirus transmission. Additionally, the discovery of these new viruses has generated interest in their potential use as biological control agents as well as novel vaccine platforms. The arbovirus community will benefit from the growing database of knowledge concerning these newly described viral endosymbionts, as their impacts will likely be far reaching.

  19. A broken promise: microbiome differential abundance methods do not control the false discovery rate.

    Science.gov (United States)

    Hawinkel, Stijn; Mattiello, Federico; Bijnens, Luc; Thas, Olivier

    2017-08-22

    High-throughput sequencing technologies allow easy characterization of the human microbiome, but the statistical methods to analyze microbiome data are still in their infancy. Differential abundance methods aim at detecting associations between the abundances of bacterial species and subject grouping factors. The results of such methods are important to identify the microbiome as a prognostic or diagnostic biomarker or to demonstrate efficacy of prodrug or antibiotic drugs. Because of a lack of benchmarking studies in the microbiome field, no consensus exists on the performance of the statistical methods. We have compared a large number of popular methods through extensive parametric and nonparametric simulation as well as real data shuffling algorithms. The results are consistent over the different approaches and all point to an alarming excess of false discoveries. This raises great doubts about the reliability of discoveries in past studies and imperils reproducibility of microbiome experiments. To further improve method benchmarking, we introduce a new simulation tool that allows to generate correlated count data following any univariate count distribution; the correlation structure may be inferred from real data. Most simulation studies discard the correlation between species, but our results indicate that this correlation can negatively affect the performance of statistical methods. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Specificity of discoveries in radiochemistry

    International Nuclear Information System (INIS)

    Krivomazov, A.N.

    1977-01-01

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

  1. 14 CFR 406.143 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  2. 30 CFR 44.24 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  3. 19 CFR 356.20 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  4. 24 CFR 180.500 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  5. 22 CFR 224.21 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  6. 19 CFR 207.109 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  7. 15 CFR 25.21 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  8. 19 CFR 354.10 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  9. 36 CFR 1150.63 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  10. 37 CFR 11.52 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  11. Specification and Validation of an Edge Router Discovery Protocol for Mobile Ad Hoc Networks

    DEFF Research Database (Denmark)

    Kristensen, Lars Michael; Jensen, Kurt

    2004-01-01

    We present an industrial project at Ericsson Telebit A/S where Coloured Petri Nets (CP-nets or CPNs) have been used for the design and specification of an edge router discovery protocol for mobile ad-hoc networks. The Edge Router Discovery Protocol (ERDP) supports an edge router in a stationary...

  12. 39 CFR 963.14 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  13. 14 CFR 16.213 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  14. 28 CFR 76.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  15. 40 CFR 27.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  16. 37 CFR 41.150 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  17. 14 CFR 13.220 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  18. 49 CFR 604.38 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  19. 15 CFR 719.10 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  20. 24 CFR 26.18 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  1. 42 CFR 426.532 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  2. 49 CFR 1503.633 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  3. 14 CFR 1264.120 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  4. 22 CFR 128.6 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  5. 24 CFR 26.42 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  6. 49 CFR 386.37 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  7. 29 CFR 1955.32 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  8. 42 CFR 426.432 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  9. 10 CFR 13.21 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  10. 49 CFR 1121.2 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  11. 38 CFR 42.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  12. 31 CFR 10.71 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  13. 39 CFR 955.15 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  14. 43 CFR 35.21 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  15. 15 CFR 766.9 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  16. 13 CFR 134.213 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  17. 31 CFR 16.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  18. 29 CFR 2200.208 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  19. 47 CFR 65.105 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  20. 49 CFR 209.313 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  1. 15 CFR 280.210 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  2. 29 CFR 2700.56 - Discovery; general.

    Science.gov (United States)

    2010-07-01

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

  3. 10 CFR 1013.21 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  4. 37 CFR 2.120 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  5. 46 CFR 550.502 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  6. 15 CFR 785.8 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  7. 22 CFR 35.21 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  8. 45 CFR 96.65 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  9. 49 CFR 31.21 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  10. 43 CFR 4.1130 - Discovery methods.

    Science.gov (United States)

    2010-10-01

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

  11. 6 CFR 13.21 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  12. 45 CFR 99.23 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  13. 20 CFR 355.21 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  14. 10 CFR 2.1018 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  15. 28 CFR 71.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  16. 13 CFR 134.310 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  17. 34 CFR 33.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  18. 28 CFR 18.7 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  19. 7 CFR 1.322 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  20. 45 CFR 1386.103 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  1. 45 CFR 79.21 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  2. 12 CFR 308.520 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  3. 47 CFR 1.729 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  4. 7 CFR 283.12 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  5. Molecular property diagnostic suite (MPDS): Development of disease-specific open source web portals for drug discovery.

    Science.gov (United States)

    Nagamani, S; Gaur, A S; Tanneeru, K; Muneeswaran, G; Madugula, S S; Consortium, Mpds; Druzhilovskiy, D; Poroikov, V V; Sastry, G N

    2017-11-01

    Molecular property diagnostic suite (MPDS) is a Galaxy-based open source drug discovery and development platform. MPDS web portals are designed for several diseases, such as tuberculosis, diabetes mellitus, and other metabolic disorders, specifically aimed to evaluate and estimate the drug-likeness of a given molecule. MPDS consists of three modules, namely data libraries, data processing, and data analysis tools which are configured and interconnected to assist drug discovery for specific diseases. The data library module encompasses vast information on chemical space, wherein the MPDS compound library comprises 110.31 million unique molecules generated from public domain databases. Every molecule is assigned with a unique ID and card, which provides complete information for the molecule. Some of the modules in the MPDS are specific to the diseases, while others are non-specific. Importantly, a suitably altered protocol can be effectively generated for another disease-specific MPDS web portal by modifying some of the modules. Thus, the MPDS suite of web portals shows great promise to emerge as disease-specific portals of great value, integrating chemoinformatics, bioinformatics, molecular modelling, and structure- and analogue-based drug discovery approaches.

  6. 42 CFR 1005.7 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  7. 29 CFR 1603.210 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  8. 45 CFR 150.435 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  9. 34 CFR 81.16 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  10. 29 CFR 1905.25 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  11. 12 CFR 1780.26 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  12. 45 CFR 160.516 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  13. 42 CFR 430.86 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  14. cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate.

    Science.gov (United States)

    Klambauer, Günter; Schwarzbauer, Karin; Mayr, Andreas; Clevert, Djork-Arné; Mitterecker, Andreas; Bodenhofer, Ulrich; Hochreiter, Sepp

    2012-05-01

    Quantitative analyses of next-generation sequencing (NGS) data, such as the detection of copy number variations (CNVs), remain challenging. Current methods detect CNVs as changes in the depth of coverage along chromosomes. Technological or genomic variations in the depth of coverage thus lead to a high false discovery rate (FDR), even upon correction for GC content. In the context of association studies between CNVs and disease, a high FDR means many false CNVs, thereby decreasing the discovery power of the study after correction for multiple testing. We propose 'Copy Number estimation by a Mixture Of PoissonS' (cn.MOPS), a data processing pipeline for CNV detection in NGS data. In contrast to previous approaches, cn.MOPS incorporates modeling of depths of coverage across samples at each genomic position. Therefore, cn.MOPS is not affected by read count variations along chromosomes. Using a Bayesian approach, cn.MOPS decomposes variations in the depth of coverage across samples into integer copy numbers and noise by means of its mixture components and Poisson distributions, respectively. The noise estimate allows for reducing the FDR by filtering out detections having high noise that are likely to be false detections. We compared cn.MOPS with the five most popular methods for CNV detection in NGS data using four benchmark datasets: (i) simulated data, (ii) NGS data from a male HapMap individual with implanted CNVs from the X chromosome, (iii) data from HapMap individuals with known CNVs, (iv) high coverage data from the 1000 Genomes Project. cn.MOPS outperformed its five competitors in terms of precision (1-FDR) and recall for both gains and losses in all benchmark data sets. The software cn.MOPS is publicly available as an R package at http://www.bioinf.jku.at/software/cnmops/ and at Bioconductor.

  15. 42 CFR 405.1037 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  16. 20 CFR 498.207 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  17. 42 CFR 93.512 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  18. 42 CFR 3.516 - Discovery.

    Science.gov (United States)

    2010-10-01

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

  19. 10 CFR 205.198 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  20. 12 CFR 908.46 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  1. 21 CFR 17.23 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  2. Two combinatorial optimization problems for SNP discovery using base-specific cleavage and mass spectrometry.

    Science.gov (United States)

    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.

  3. Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate

    Science.gov (United States)

    Andreassen, Ole A.; Thompson, Wesley K.; Schork, Andrew J.; Ripke, Stephan; Mattingsdal, Morten; Kelsoe, John R.; Kendler, Kenneth S.; O'Donovan, Michael C.; Rujescu, Dan; Werge, Thomas; Sklar, Pamela; Roddey, J. Cooper; Chen, Chi-Hua; McEvoy, Linda; Desikan, Rahul S.; Djurovic, Srdjan; Dale, Anders M.

    2013-01-01

    Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional Q–Q curves of data from the Psychiatric Genome Consortium (SCZ; n = 9,379 cases and n = 7,736 controls; BD: n = 6,990 cases and n = 4,820 controls) to show enrichment of SNPs associated with SCZ as a function of association with BD and vice versa with a corresponding reduction in FDR. Applying the conditional FDR method, we identified 58 loci associated with SCZ and 35 loci associated with BD below the conditional FDR level of 0.05. Of these, 14 loci were associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders. PMID:23637625

  4. cn.FARMS: a latent variable model to detect copy number variations in microarray data with a low false discovery rate.

    Science.gov (United States)

    Clevert, Djork-Arné; Mitterecker, Andreas; Mayr, Andreas; Klambauer, Günter; Tuefferd, Marianne; De Bondt, An; Talloen, Willem; Göhlmann, Hinrich; Hochreiter, Sepp

    2011-07-01

    Cost-effective oligonucleotide genotyping arrays like the Affymetrix SNP 6.0 are still the predominant technique to measure DNA copy number variations (CNVs). However, CNV detection methods for microarrays overestimate both the number and the size of CNV regions and, consequently, suffer from a high false discovery rate (FDR). A high FDR means that many CNVs are wrongly detected and therefore not associated with a disease in a clinical study, though correction for multiple testing takes them into account and thereby decreases the study's discovery power. For controlling the FDR, we propose a probabilistic latent variable model, 'cn.FARMS', which is optimized by a Bayesian maximum a posteriori approach. cn.FARMS controls the FDR through the information gain of the posterior over the prior. The prior represents the null hypothesis of copy number 2 for all samples from which the posterior can only deviate by strong and consistent signals in the data. On HapMap data, cn.FARMS clearly outperformed the two most prevalent methods with respect to sensitivity and FDR. The software cn.FARMS is publicly available as a R package at http://www.bioinf.jku.at/software/cnfarms/cnfarms.html.

  5. 45 CFR 213.23a - Discovery.

    Science.gov (United States)

    2010-10-01

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

  6. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  7. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  8. Rapid discovery of peptide capture candidates with demonstrated specificity for structurally similar toxins

    Science.gov (United States)

    Sarkes, Deborah A.; Hurley, Margaret M.; Coppock, Matthew B.; Farrell, Mikella E.; Pellegrino, Paul M.; Stratis-Cullum, Dimitra N.

    2016-05-01

    Peptides have emerged as viable alternatives to antibodies for molecular-based sensing due to their similarity in recognition ability despite their relative structural simplicity. Various methods for peptide capture reagent discovery exist, including phage display, yeast display, and bacterial display. One of the primary advantages of peptide discovery by bacterial display technology is the speed to candidate peptide capture agent, due to both rapid growth of bacteria and direct utilization of the sorted cells displaying each individual peptide for the subsequent round of biopanning. We have previously isolated peptide affinity reagents towards protective antigen of Bacillus anthracis using a commercially available automated magnetic sorting platform with improved enrichment as compared to manual magnetic sorting. In this work, we focus on adapting our automated biopanning method to a more challenging sort, to demonstrate the specificity possible with peptide capture agents. This was achieved using non-toxic, recombinant variants of ricin and abrin, RiVax and abrax, respectively, which are structurally similar Type II ribosomal inactivating proteins with significant sequence homology. After only two rounds of biopanning, enrichment of peptide capture candidates binding abrax but not RiVax was achieved as demonstrated by Fluorescence Activated Cell Sorting (FACS) studies. Further sorting optimization included negative sorting against RiVax, proper selection of autoMACS programs for specific sorting rounds, and using freshly made buffer and freshly thawed protein target for each round of biopanning for continued enrichment over all four rounds. Most of the resulting candidates from biopanning for abrax binding peptides were able to bind abrax but not RiVax, demonstrating that short peptide sequences can be highly specific even at this early discovery stage.

  9. 12 CFR 747.24 - Scope of document discovery.

    Science.gov (United States)

    2010-01-01

    ... act of Congress, or the principles of common law provide. (d) Time limits. All discovery, including... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Scope of document discovery. 747.24 Section 747... of Practice and Procedure § 747.24 Scope of document discovery. (a) Limits on discovery. (1) Subject...

  10. 7 CFR 283.28 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  11. 12 CFR 509.102 - Discovery.

    Science.gov (United States)

    2010-01-01

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

  12. Improving sensitivity in proteome studies by analysis of false discovery rates for multiple search engines.

    Science.gov (United States)

    Jones, Andrew R; Siepen, Jennifer A; Hubbard, Simon J; Paton, Norman W

    2009-03-01

    LC-MS experiments can generate large quantities of data, for which a variety of database search engines are available to make peptide and protein identifications. Decoy databases are becoming widely used to place statistical confidence in result sets, allowing the false discovery rate (FDR) to be estimated. Different search engines produce different identification sets so employing more than one search engine could result in an increased number of peptides (and proteins) being identified, if an appropriate mechanism for combining data can be defined. We have developed a search engine independent score, based on FDR, which allows peptide identifications from different search engines to be combined, called the FDR Score. The results demonstrate that the observed FDR is significantly different when analysing the set of identifications made by all three search engines, by each pair of search engines or by a single search engine. Our algorithm assigns identifications to groups according to the set of search engines that have made the identification, and re-assigns the score (combined FDR Score). The combined FDR Score can differentiate between correct and incorrect peptide identifications with high accuracy, allowing on average 35% more peptide identifications to be made at a fixed FDR than using a single search engine.

  13. The Goal Specificity Effect on Strategy Use and Instructional Efficiency during Computer-Based Scientific Discovery Learning

    Science.gov (United States)

    Kunsting, Josef; Wirth, Joachim; Paas, Fred

    2011-01-01

    Using a computer-based scientific discovery learning environment on buoyancy in fluids we investigated the "effects of goal specificity" (nonspecific goals vs. specific goals) for two goal types (problem solving goals vs. learning goals) on "strategy use" and "instructional efficiency". Our empirical findings close an important research gap,…

  14. Discovery of cancer common and specific driver gene sets

    Science.gov (United States)

    2017-01-01

    Abstract Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found. PMID:28168295

  15. 40 CFR 209.22 - Other discovery.

    Science.gov (United States)

    2010-07-01

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

  16. Amnesiacs might get the gist: reduced false recognition in amnesia may be the result of impaired item-specific memory.

    Science.gov (United States)

    Nissan, Jack; Abrahams, Sharon; Sala, Sergio Della

    2013-01-01

    It is a common finding in tests of false recognition that amnesic patients recognize fewer related lures than healthy controls, and this has led to assumptions that gist memory is damaged in these patients (Schacter, Verfaellie, & Anes, 1997, Neuropsychology, 11; Schacter, Verfaellie, Anes, & Racine, 1998, Journal of Cognitive Neuroscience, 10; Schacter, Verfaellie, & Pradere, 1996, Journal of Memory and Language, 35). However, clinical observations find that amnesic patients typically hold meaningful conversations and make relevant remarks, and there is some experimental evidence highlighting preserved immediate recall of prose (Baddeley & Wilson, 2002, Neuropsychologia, 40; Gooding, Isaac, & Mayes, 2005, Neuropsychologia, 43; Rosenbaum, Gilboa, Levine, Winocur, & Moscovitch, 2009, Neuropsychologia, 47), which suggests that amnesiacs can get the gist. The present experiment used false recognition paradigms to assess whether the reduced rate of false recognition found in amnesic patients may be a consequence of their impaired item-specific memory. It examined the effect of increasing the item-specific memory of amnesic patient DA by bringing her to criterion on relevant study-lists and compared her performance on a false recognition paradigm with a group of 32 healthy young adults. Results indicated that when DA's item-specific memory was increased she was more able to gist and her performance was no different to the healthy young adults. Previous assumptions that gist memory is necessarily damaged in amnesia might therefore be revisited, since the reduced rate of false recognition could be caused by impaired item-specific memory. The experiment also highlights a positive relationship between item-specific and gist memory which has not previously been accounted for in false-recognition experiments.

  17. 19 CFR 210.61 - Discovery and compulsory process.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery and compulsory process. 210.61 Section 210.61 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Temporary Relief § 210.61 Discovery and compulsory...

  18. 19 CFR 210.27 - General provisions governing discovery.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false General provisions governing discovery. 210.27 Section 210.27 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Discovery and Compulsory Process § 210.27 General...

  19. HANDS: a tool for genome-wide discovery of subgenome-specific base-identity in polyploids.

    KAUST Repository

    Mithani, Aziz; Belfield, Eric J; Brown, Carly; Jiang, Caifu; Leach, Lindsey J; Harberd, Nicholas P

    2013-01-01

    The analysis of polyploid genomes is problematic because homeologous subgenome sequences are closely related. This relatedness makes it difficult to assign individual sequences to the specific subgenome from which they are derived, and hinders the development of polyploid whole genome assemblies.We here present a next-generation sequencing (NGS)-based approach for assignment of subgenome-specific base-identity at sites containing homeolog-specific polymorphisms (HSPs): 'HSP base Assignment using NGS data through Diploid Similarity' (HANDS). We show that HANDS correctly predicts subgenome-specific base-identity at >90% of assayed HSPs in the hexaploid bread wheat (Triticum aestivum) transcriptome, thus providing a substantial increase in accuracy versus previous methods for homeolog-specific base assignment.We conclude that HANDS enables rapid and accurate genome-wide discovery of homeolog-specific base-identity, a capability having multiple applications in polyploid genomics.

  20. HANDS: a tool for genome-wide discovery of subgenome-specific base-identity in polyploids.

    KAUST Repository

    Mithani, Aziz

    2013-09-24

    The analysis of polyploid genomes is problematic because homeologous subgenome sequences are closely related. This relatedness makes it difficult to assign individual sequences to the specific subgenome from which they are derived, and hinders the development of polyploid whole genome assemblies.We here present a next-generation sequencing (NGS)-based approach for assignment of subgenome-specific base-identity at sites containing homeolog-specific polymorphisms (HSPs): \\'HSP base Assignment using NGS data through Diploid Similarity\\' (HANDS). We show that HANDS correctly predicts subgenome-specific base-identity at >90% of assayed HSPs in the hexaploid bread wheat (Triticum aestivum) transcriptome, thus providing a substantial increase in accuracy versus previous methods for homeolog-specific base assignment.We conclude that HANDS enables rapid and accurate genome-wide discovery of homeolog-specific base-identity, a capability having multiple applications in polyploid genomics.

  1. 40 CFR 22.52 - Information exchange and discovery.

    Science.gov (United States)

    2010-07-01

    ... Procedure Act § 22.52 Information exchange and discovery. Respondent's information exchange pursuant to § 22.19(a) shall include information on any economic benefit resulting from any activity or failure to act... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Information exchange and discovery. 22...

  2. False-positive findings in mammography screening induces short-term distress - breast cancer-specific concern prevails longer

    DEFF Research Database (Denmark)

    Aro, A R; Pilvikki Absetz, S; van Elderen, T M

    2000-01-01

    -ups at 2 and 12 months postscreening. At 2 months, there was a moderate multivariate effect of group on distress; and intrusive thinking and worry about breast cancer, in particular, were most frequent amongst the false positives. Intrusive thinking still prevailed at 12 months, in addition to a higher...... findings (n=1407), false-positive findings (n=492) and referents from outside the screening programme (n=1718, age 48-49 years). Distress was measured as illness worry, anxiety, depression, cancer beliefs and early detection behaviour. Measurements were one month before screening invitation with follow...... perceived breast cancer risk and susceptibility. Distress related to screening and false-positive findings seems to be moderate, but prevailing cancer-specific concerns call for improvements in screening programmes....

  3. Integrated Proteomic Pipeline Using Multiple Search Engines for a Proteogenomic Study with a Controlled Protein False Discovery Rate.

    Science.gov (United States)

    Park, Gun Wook; Hwang, Heeyoun; Kim, Kwang Hoe; Lee, Ju Yeon; Lee, Hyun Kyoung; Park, Ji Yeong; Ji, Eun Sun; Park, Sung-Kyu Robin; Yates, John R; Kwon, Kyung-Hoon; Park, Young Mok; Lee, Hyoung-Joo; Paik, Young-Ki; Kim, Jin Young; Yoo, Jong Shin

    2016-11-04

    In the Chromosome-Centric Human Proteome Project (C-HPP), false-positive identification by peptide spectrum matches (PSMs) after database searches is a major issue for proteogenomic studies using liquid-chromatography and mass-spectrometry-based large proteomic profiling. Here we developed a simple strategy for protein identification, with a controlled false discovery rate (FDR) at the protein level, using an integrated proteomic pipeline (IPP) that consists of four engrailed steps as follows. First, using three different search engines, SEQUEST, MASCOT, and MS-GF+, individual proteomic searches were performed against the neXtProt database. Second, the search results from the PSMs were combined using statistical evaluation tools including DTASelect and Percolator. Third, the peptide search scores were converted into E-scores normalized using an in-house program. Last, ProteinInferencer was used to filter the proteins containing two or more peptides with a controlled FDR of 1.0% at the protein level. Finally, we compared the performance of the IPP to a conventional proteomic pipeline (CPP) for protein identification using a controlled FDR of <1% at the protein level. Using the IPP, a total of 5756 proteins (vs 4453 using the CPP) including 477 alternative splicing variants (vs 182 using the CPP) were identified from human hippocampal tissue. In addition, a total of 10 missing proteins (vs 7 using the CPP) were identified with two or more unique peptides, and their tryptic peptides were validated using MS/MS spectral pattern from a repository database or their corresponding synthetic peptides. This study shows that the IPP effectively improved the identification of proteins, including alternative splicing variants and missing proteins, in human hippocampal tissues for the C-HPP. All RAW files used in this study were deposited in ProteomeXchange (PXD000395).

  4. 10 CFR 2.709 - Discovery against NRC staff.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Discovery against NRC staff. 2.709 Section 2.709 Energy... Rules for Formal Adjudications § 2.709 Discovery against NRC staff. (a)(1) In a proceeding in which the NRC staff is a party, the NRC staff will make available one or more witnesses, designated by the...

  5. 5 CFR 185.122 - Discovery.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Discovery. 185.122 Section 185.122 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PROGRAM FRAUD CIVIL REMEDIES..., answers, records, accounts, papers, and other data and documentary evidence. Nothing contained herein...

  6. A large-scale chromosome-specific SNP discovery guideline.

    Science.gov (United States)

    Akpinar, Bala Ani; Lucas, Stuart; Budak, Hikmet

    2017-01-01

    Single-nucleotide polymorphisms (SNPs) are the most prevalent type of variation in genomes that are increasingly being used as molecular markers in diversity analyses, mapping and cloning of genes, and germplasm characterization. However, only a few studies reported large-scale SNP discovery in Aegilops tauschii, restricting their potential use as markers for the low-polymorphic D genome. Here, we report 68,592 SNPs found on the gene-related sequences of the 5D chromosome of Ae. tauschii genotype MvGB589 using genomic and transcriptomic sequences from seven Ae. tauschii accessions, including AL8/78, the only genotype for which a draft genome sequence is available at present. We also suggest a workflow to compare SNP positions in homologous regions on the 5D chromosome of Triticum aestivum, bread wheat, to mark single nucleotide variations between these closely related species. Overall, the identified SNPs define a density of 4.49 SNPs per kilobyte, among the highest reported for the genic regions of Ae. tauschii so far. To our knowledge, this study also presents the first chromosome-specific SNP catalog in Ae. tauschii that should facilitate the association of these SNPs with morphological traits on chromosome 5D to be ultimately targeted for wheat improvement.

  7. Use of the local false discovery rate for identification of metabolic biomarkers in rat urine following Genkwa Flos-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Zuojing Li

    Full Text Available Metabolomics is concerned with characterizing the large number of metabolites present in a biological system using nuclear magnetic resonance (NMR and HPLC/MS (high-performance liquid chromatography with mass spectrometry. Multivariate analysis is one of the most important tools for metabolic biomarker identification in metabolomic studies. However, analyzing the large-scale data sets acquired during metabolic fingerprinting is a major challenge. As a posterior probability that the features of interest are not affected, the local false discovery rate (LFDR is a good interpretable measure. However, it is rarely used to when interrogating metabolic data to identify biomarkers. In this study, we employed the LFDR method to analyze HPLC/MS data acquired from a metabolomic study of metabolic changes in rat urine during hepatotoxicity induced by Genkwa flos (GF treatment. The LFDR approach was successfully used to identify important rat urine metabolites altered by GF-stimulated hepatotoxicity. Compared with principle component analysis (PCA, LFDR is an interpretable measure and discovers more important metabolites in an HPLC/MS-based metabolomic study.

  8. False discovery rate control incorporating phylogenetic tree increases detection power in microbiome-wide multiple testing.

    Science.gov (United States)

    Xiao, Jian; Cao, Hongyuan; Chen, Jun

    2017-09-15

    Next generation sequencing technologies have enabled the study of the human microbiome through direct sequencing of microbial DNA, resulting in an enormous amount of microbiome sequencing data. One unique characteristic of microbiome data is the phylogenetic tree that relates all the bacterial species. Closely related bacterial species have a tendency to exhibit a similar relationship with the environment or disease. Thus, incorporating the phylogenetic tree information can potentially improve the detection power for microbiome-wide association studies, where hundreds or thousands of tests are conducted simultaneously to identify bacterial species associated with a phenotype of interest. Despite much progress in multiple testing procedures such as false discovery rate (FDR) control, methods that take into account the phylogenetic tree are largely limited. We propose a new FDR control procedure that incorporates the prior structure information and apply it to microbiome data. The proposed procedure is based on a hierarchical model, where a structure-based prior distribution is designed to utilize the phylogenetic tree. By borrowing information from neighboring bacterial species, we are able to improve the statistical power of detecting associated bacterial species while controlling the FDR at desired levels. When the phylogenetic tree is mis-specified or non-informative, our procedure achieves a similar power as traditional procedures that do not take into account the tree structure. We demonstrate the performance of our method through extensive simulations and real microbiome datasets. We identified far more alcohol-drinking associated bacterial species than traditional methods. R package StructFDR is available from CRAN. chen.jun2@mayo.edu. 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

  9. The value of prostate specific antigen and prostate specific antigen density in the diagnosis ad treatment of prostate cancer

    International Nuclear Information System (INIS)

    Hu Guoying; Yu Mingqi; Feng Xinli

    2001-01-01

    To study the clinical value of prostate specific antigen (PSA) and prostate specific antigen density (PSAD), the PSA levels of pre-and post-treatment were measured in 28 cases with prostate cancer (Pca) and 80 patients with being Prostate hyperplasia (BPH). PASD was measured in 18 cases Pca and 50 cases BPH of them. The results suggest that the sensitivity, specificity and accuracy of diagnosis for Pca were 85.7%, 80.0% and 81.4%, respectively. The false positive rate was 20%. PSAD is superior to PSA in distinguishing prostate cancer from benign prostate hyperplasia. The false positive rate was only 6%. But in the clinical application, the authors should combine PASD with other materials. The regular observation of post therapeutic PSA is of great value to the earlier discovery of local recurrence and metastasis as well as the judgement of curative effect and prognosis

  10. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

  11. Bioinformatics for discovery of microbiome variation

    DEFF Research Database (Denmark)

    Brejnrod, Asker Daniel

    of various molecular methods to build hypotheses about the impact of a copper contaminated soil. The introduction is a broad introduction to the field of microbiome research with a focus on the technologies that enable these discoveries and how some of the broader issues have related to this thesis......Sequencing based tools have revolutionized microbiology in recent years. Highthroughput DNA sequencing have allowed high-resolution studies on microbial life in many different environments and at unprecedented low cost. These culture-independent methods have helped discovery of novel bacteria...... 1 ,“Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies”, benchmarked the performance of a variety of popular statistical methods for discovering differentially abundant bacteria . between...

  12. 41 CFR 105-70.021 - Discovery.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Discovery. 105-70.021 Section 105-70.021 Public Contracts and Property Management Federal Property Management Regulations System..., papers, and other data and documentary evidence. Nothing contained herein shall be interpreted to require...

  13. Assessment of Metabolome Annotation Quality: A Method for Evaluating the False Discovery Rate of Elemental Composition Searches

    Science.gov (United States)

    Matsuda, Fumio; Shinbo, Yoko; Oikawa, Akira; Hirai, Masami Yokota; Fiehn, Oliver; Kanaya, Shigehiko; Saito, Kazuki

    2009-01-01

    Background In metabolomics researches using mass spectrometry (MS), systematic searching of high-resolution mass data against compound databases is often the first step of metabolite annotation to determine elemental compositions possessing similar theoretical mass numbers. However, incorrect hits derived from errors in mass analyses will be included in the results of elemental composition searches. To assess the quality of peak annotation information, a novel methodology for false discovery rates (FDR) evaluation is presented in this study. Based on the FDR analyses, several aspects of an elemental composition search, including setting a threshold, estimating FDR, and the types of elemental composition databases most reliable for searching are discussed. Methodology/Principal Findings The FDR can be determined from one measured value (i.e., the hit rate for search queries) and four parameters determined by Monte Carlo simulation. The results indicate that relatively high FDR values (30–50%) were obtained when searching time-of-flight (TOF)/MS data using the KNApSAcK and KEGG databases. In addition, searches against large all-in-one databases (e.g., PubChem) always produced unacceptable results (FDR >70%). The estimated FDRs suggest that the quality of search results can be improved not only by performing more accurate mass analysis but also by modifying the properties of the compound database. A theoretical analysis indicates that FDR could be improved by using compound database with smaller but higher completeness entries. Conclusions/Significance High accuracy mass analysis, such as Fourier transform (FT)-MS, is needed for reliable annotation (FDR metabolome data. PMID:19847304

  14. Reducing false-positive incidental findings with ensemble genotyping and logistic regression based variant filtering methods.

    Science.gov (United States)

    Hwang, Kyu-Baek; Lee, In-Hee; Park, Jin-Ho; Hambuch, Tina; Choe, Yongjoon; Kim, MinHyeok; Lee, Kyungjoon; Song, Taemin; Neu, Matthew B; Gupta, Neha; Kohane, Isaac S; Green, Robert C; Kong, Sek Won

    2014-08-01

    As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false-positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here, we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false-negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous single nucleotide variants (SNVs); 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery in NA12878, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and an ensemble genotyping would be essential to minimize false-positive DNM candidates. © 2014 WILEY PERIODICALS, INC.

  15. Resource Discovery in Activity-Based Sensor Networks

    DEFF Research Database (Denmark)

    Bucur, Doina; Bardram, Jakob

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

  16. 19 CFR 210.33 - Failure to make or cooperate in discovery; sanctions.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Failure to make or cooperate in discovery; sanctions. 210.33 Section 210.33 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Discovery and Compulsory Process...

  17. Sample size calculation while controlling false discovery rate for differential expression analysis with RNA-sequencing experiments.

    Science.gov (United States)

    Bi, Ran; Liu, Peng

    2016-03-31

    RNA-Sequencing (RNA-seq) experiments have been popularly applied to transcriptome studies in recent years. Such experiments are still relatively costly. As a result, RNA-seq experiments often employ a small number of replicates. Power analysis and sample size calculation are challenging in the context of differential expression analysis with RNA-seq data. One challenge is that there are no closed-form formulae to calculate power for the popularly applied tests for differential expression analysis. In addition, false discovery rate (FDR), instead of family-wise type I error rate, is controlled for the multiple testing error in RNA-seq data analysis. So far, there are very few proposals on sample size calculation for RNA-seq experiments. In this paper, we propose a procedure for sample size calculation while controlling FDR for RNA-seq experimental design. Our procedure is based on the weighted linear model analysis facilitated by the voom method which has been shown to have competitive performance in terms of power and FDR control for RNA-seq differential expression analysis. We derive a method that approximates the average power across the differentially expressed genes, and then calculate the sample size to achieve a desired average power while controlling FDR. Simulation results demonstrate that the actual power of several popularly applied tests for differential expression is achieved and is close to the desired power for RNA-seq data with sample size calculated based on our method. Our proposed method provides an efficient algorithm to calculate sample size while controlling FDR for RNA-seq experimental design. We also provide an R package ssizeRNA that implements our proposed method and can be downloaded from the Comprehensive R Archive Network ( http://cran.r-project.org ).

  18. 40 CFR 164.51 - Other discovery.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Other discovery. 164.51 Section 164.51... GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS TO... OTHER HEARINGS CALLED PURSUANT TO SECTION 6 OF THE ACT General Rules of Practice Concerning Proceedings...

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

    Science.gov (United States)

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

    2015-01-21

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

  20. Representation Discovery using Harmonic Analysis

    CERN Document Server

    Mahadevan, Sridhar

    2008-01-01

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

  1. Too Good to be False: Nonsignificant Results Revisited

    Directory of Open Access Journals (Sweden)

    Chris H. J. Hartgerink

    2017-03-01

    Full Text Available Due to its probabilistic nature, Null Hypothesis Significance Testing (NHST is subject to decision errors. The concern for false positives has overshadowed the concern for false negatives in the recent debates in psychology. This might be unwarranted, since reported statistically nonsignificant findings may just be ‘too good to be false’. We examined evidence for false negatives in nonsignificant results in three different ways. We adapted the Fisher test to detect the presence of at least one false negative in a set of statistically nonsignificant results. Simulations show that the adapted Fisher method generally is a powerful method to detect false negatives. We examined evidence for false negatives in the psychology literature in three applications of the adapted Fisher method. These applications indicate that (i the observed effect size distribution of nonsignificant effects exceeds the expected distribution assuming a null-effect, and approximately two out of three (66.7% psychology articles reporting nonsignificant results contain evidence for at least one false negative, (ii nonsignificant results on gender effects contain evidence of true nonzero effects, and (iii the statistically nonsignificant replications from the Reproducibility Project Psychology (RPP do not warrant strong conclusions about the absence or presence of true zero effects underlying these nonsignificant results. We conclude that false negatives deserve more attention in the current debate on statistical practices in psychology. Potentially neglecting effects due to a lack of statistical power can lead to a waste of research resources and stifle the scientific discovery process.

  2. 48 CFR 22.1015 - Discovery of errors by the Department of Labor.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Discovery of errors by the... REGULATION SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Service Contract Act of 1965, as Amended 22.1015 Discovery of errors by the Department of Labor. If the Department of...

  3. False-positive findings in mammography screening induces short-term distress - breast cancer-specific concern prevails longer

    DEFF Research Database (Denmark)

    Aro, A R; Pilvikki Absetz, S; van Elderen, T M

    2000-01-01

    The aim of this study was to examine psychological distress in a mammography screening process as a consequence of screening after adjusting for background, personality and prescreening distress. Subjects, aged 50 years, were invitees at their first screening. There were three groups; normal find...... perceived breast cancer risk and susceptibility. Distress related to screening and false-positive findings seems to be moderate, but prevailing cancer-specific concerns call for improvements in screening programmes....

  4. False positive and false negative FDG-PET scans in various thoracic diseases

    International Nuclear Information System (INIS)

    Chang, Jung Min; Lee, Hyun Ju; Goo, Jin Mo; Lee, Ho Young; Lee, Jong Jin; Chung, June Key; Im, Jung Gi

    2006-01-01

    Fluorodeoxygucose (FDG)-positron emission tomography (PET) is being used more and more to differentiate benign form malignant focal lesions and it has been shown to be more efficacious than conventional chest computed tomography (CT). However, FDG is not a cancer-specific agent, and false positive findings in benign diseases have been reported. Infectious diseases (mycobacterial, fungal, bacterial infection), sarcoidosis, radiation pneumonitis and post-operative surgical conditions have shown intense uptake on PET scan. On the other hand, tumors with low glycolytic activity such as adenomas, bronchioloalveolar carcinomas, carcinoid tumors, low grade lymphomas and small sized tumors have revealed false negative findings on PET scan, Furthermore, in diseases located near the physiologic uptake sites (heart, bladder, kidney, and liver), FDG-PET should be complemented with other imaging modalities to confirm results and to minimize false negative findings. Familiarity with these false positive and negative findings will help radiologists interpret PET scans more accurately and also will help to determine the significance of the findings. In this review, we illustrate false positive and negative findings of PET scan in a variety of diseases

  5. 45 CFR 681.18 - What type of discovery is authorized and how is it conducted?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false What type of discovery is authorized and how is it... SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Hearing Procedures § 681.18 What type of discovery is authorized and how is it conducted? (a) The following types of discovery are authorized: (1...

  6. 'False-positive' and 'false-negative' test results in clinical urine drug testing.

    Science.gov (United States)

    Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L

    2009-08-01

    The terms 'false-positive' and 'false-negative' are widely used in discussions of urine drug test (UDT) results. These terms are inadequate because they are used in different ways by physicians and laboratory professionals and they are too narrow to encompass the larger universe of potentially misleading, inappropriate and unexpected drug test results. This larger universe, while not solely comprised of technically 'true' or 'false' positive or negative test results, presents comparable interpretive challenges with corresponding clinical implications. In this review, we propose the terms 'potentially inappropriate' positive or negative test results in reference to UDT results that are ambiguous or unexpected and subject to misinterpretation. Causes of potentially inappropriate positive UDT results include in vivo metabolic conversions of a drug, exposure to nonillicit sources of a drug and laboratory error. Causes of potentially inappropriate negative UDT results include limited assay specificity, absence of drug in the urine, presence of drug in the urine, but below established assay cutoff, specimen manipulation and laboratory error. Clinical UDT interpretation is a complicated task requiring knowledge of recent prescription, over-the-counter and herbal drug administration, drug metabolism and analytical sensitivities and specificities.

  7. Activity artifacts in drug discovery and different facets of compound promiscuity [v1; ref status: indexed, http://f1000r.es/4gz

    Directory of Open Access Journals (Sweden)

    Jürgen Bajorath

    2014-10-01

    Full Text Available Compounds with apparent activity in a variety of assays might disable target proteins or produce false assay signals in the absence of specific interactions. In some instances, such effects are easy to detect, in others they are not. Observed promiscuity of compounds might be due to such non-specific assay artifacts. By contrast, promiscuity might also result from specific interactions with multiple targets. In the latter case, promiscuous compounds can be attractive candidates for certain therapeutic applications. However, compounds with artificial activity readouts are often not recognized and are further progressed, which presents a substantial problem for drug discovery. In this context, the concept of PAINS (pan-assay interference compounds should be seriously considered, which makes it possible to eliminate flawed compounds from the discovery pipeline, even if their activities appear to be sound at a first glance.

  8. With sadness comes accuracy; with happiness, false memory: mood and the false memory effect.

    Science.gov (United States)

    Storbeck, Justin; Clore, Gerald L

    2005-10-01

    The Deese-Roediger-McDermott paradigm lures people to produce false memories. Two experiments examined whether induced positive or negative moods would influence this false memory effect. The affect-as-information hypothesis predicts that, on the one hand, positive affective cues experienced as task-relevant feedback encourage relational processing during encoding, which should enhance false memory effects. On the other hand, negative affective cues are hypothesized to encourage item-specific processing at encoding, which should discourage such effects. The results of Experiment 1 are consistent with these predictions: Individuals in negative moods were significantly less likely to show false memory effects than those in positive moods or those whose mood was not manipulated. Experiment 2 introduced inclusion instructions to investigate whether moods had their effects at encoding or retrieval. The results replicated the false memory finding of Experiment 1 and provide evidence that moods influence the accessibility of lures at encoding, rather than influencing monitoring at retrieval of whether lures were actually presented.

  9. Evidence of a false thumb in a fossil carnivore clarifies the evolution of pandas

    OpenAIRE

    Salesa, Manuel J.; Antón, Mauricio; Peigné, Stéphane; Morales, Jorge

    2005-01-01

    The “false thumb” of pandas is a carpal bone, the radial sesamoid, which has been enlarged and functions as an opposable thumb. If the giant panda (Ailuropoda melanoleuca) and the red panda (Ailurus fulgens) are not closely related, their sharing of this adaptation implies a remarkable convergence. The discovery of previously unknown postcranial remains of a Miocene red panda relative, Simocyon batalleri, from the Spanish site of Batallones-1 (Madrid), now shows that this animal had a false t...

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

    Directory of Open Access Journals (Sweden)

    Nicholas Ekow Thomford

    2018-05-01

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

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

    Science.gov (United States)

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

    2018-05-25

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

  12. 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.

  13. Deep Learning in Drug Discovery.

    Science.gov (United States)

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

    2016-01-01

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

  14. Comparison of seven methods for producing Affymetrix expression scores based on False Discovery Rates in disease profiling data

    Directory of Open Access Journals (Sweden)

    Gruber Stephen B

    2005-02-01

    Full Text Available Abstract Background A critical step in processing oligonucleotide microarray data is combining the information in multiple probes to produce a single number that best captures the expression level of a RNA transcript. Several systematic studies comparing multiple methods for array processing have used tightly controlled calibration data sets as the basis for comparison. Here we compare performances for seven processing methods using two data sets originally collected for disease profiling studies. An emphasis is placed on understanding sensitivity for detecting differentially expressed genes in terms of two key statistical determinants: test statistic variability for non-differentially expressed genes, and test statistic size for truly differentially expressed genes. Results In the two data sets considered here, up to seven-fold variation across the processing methods was found in the number of genes detected at a given false discovery rate (FDR. The best performing methods called up to 90% of the same genes differentially expressed, had less variable test statistics under randomization, and had a greater number of large test statistics in the experimental data. Poor performance of one method was directly tied to a tendency to produce highly variable test statistic values under randomization. Based on an overall measure of performance, two of the seven methods (Dchip and a trimmed mean approach are superior in the two data sets considered here. Two other methods (MAS5 and GCRMA-EB are inferior, while results for the other three methods are mixed. Conclusions Choice of processing method has a major impact on differential expression analysis of microarray data. Previously reported performance analyses using tightly controlled calibration data sets are not highly consistent with results reported here using data from human tissue samples. Performance of array processing methods in disease profiling and other realistic biological studies should be

  15. Application of false discovery rate control in the assessment of decrease of FDG uptake in early Alzheimer dementia

    International Nuclear Information System (INIS)

    Lee, Dong Soo; Kang, Hye Jin; Jang, Myung Jin; Kang, Won Jun; Lee, Jae Sung; Kang, Eun Joo; Lee, Kang Uk; Woo, Jong In; Lee, Myung Chul; Cho, Sang Soo

    2003-01-01

    Determining an appropriate thresholding is crucial for PDG PET analysis since strong control of Type I error could fail to find pathological differences between early Alzheimer' disease (AD) patients and healthy normal controls. We compared the SPM results on FDG PET imaging of early AD using uncorrected p-value, random-field based corrected p-value and false discovery rate (FDR) control. Twenty-eight patients (66±7 years old) with early AD and 18 age-matched normal controls (68±6 years old) underwent FDG brain PET. To identify brain regions with hypo-metabolism in group or individual patient compared to normal controls, group images or each patient's image was compared with normal controls using the same fixed p-value of 0.001 on uncorrected thresholding, random-field based corrected thresholding and FDR control. The number of hypo-metabolic voxels was smallest in corrected p-value method, largest in uncorrected p-value method and intermediate in FDG thresholding in group analysis. Three types of result pattern were found. The first was that corrected p-value did yield any voxel positive but FDR gave a few significantly hypometabolic voxels (8/28, 29%). The second was that both corrected p-value and FDR did not yield any positive region but numerous positive voxels were found with the threshold of uncorrected p-values (6/28, 21%). The last was that FDR was detected as many positive voxels as uncorrected p-value method (14/28, 50%). Conclusions FDR control could identify hypo-metabolic areas in group or individual patients with early AD. We recommend FDR control instead of uncorrected or random-field corrected thresholding method to find the areas showing hypometabolism especially in small group or individual analysis of FDG PET

  16. 29 CFR 2580.412-19 - Term of the bond, discovery period, other bond clauses.

    Science.gov (United States)

    2010-07-01

    ... SECURITY ACT OF 1974 TEMPORARY BONDING RULES General Bond Rules § 2580.412-19 Term of the bond, discovery... 29 Labor 9 2010-07-01 2010-07-01 false Term of the bond, discovery period, other bond clauses... new bond must be obtained each year. There is nothing in the Act that prohibits a bond for a term...

  17. Usability Test Results for a Discovery Tool in an Academic Library

    Directory of Open Access Journals (Sweden)

    Jody Condit Fagan

    2008-03-01

    Full Text Available Discovery tools are emerging in libraries. These tools offer library patrons the ability to concurrently search the library catalog and journal articles. While vendors rush to provide feature-rich interfaces and access to as much content as possible, librarians wonder about the usefulness of these tools to library patrons. In order to learn about both the utility and usability of EBSCO Discovery Service, James Madison University conducted a usability test with eight students and two faculty members. The test consisted of nine tasks focused on common patron requests or related to the utility of specific discovery tool features. Software recorded participants’ actions and time on task, human observers judged the success of each task, and a post-survey questionnaire gathered qualitative feedback and comments from the participants.  Overall, participants were successful at most tasks, but specific usability problems suggested some interface changes for both EBSCO Discovery Service and JMU’s customizations of the tool.  The study also raised several questions for libraries above and beyond any specific discovery tool interface, including the scope and purpose of a discovery tool versus other library systems, working with the large result sets made possible by discovery tools, and navigation between the tool and other library services and resources.  This article will be of interest to those who are investigating discovery tools, selecting products, integrating discovery tools into a library web presence, or performing evaluations of similar systems.

  18. New false color mapping for image fusion

    NARCIS (Netherlands)

    Toet, A.; Walraven, J.

    1996-01-01

    A pixel based colour mapping algorithm is presented that produces a fused false colour rendering of two gray level images representing different sensor modalities. The result-ing fused false colour images have a higher information content than each of the original images and retain sensor-specific

  19. Resource Discovery in Activity-Based Sensor Networks

    DEFF Research Database (Denmark)

    Bucur, Doina; Bardram, Jakob

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

  20. 45 CFR 2554.25 - What type of discovery is authorized and how is it conducted?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false What type of discovery is authorized and how is it...) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Hearing Provisions § 2554.25 What type of discovery is authorized and how is it conducted? (a) The following types of...

  1. Diagnosing periprosthetic infection: false-positive intraoperative Gram stains.

    Science.gov (United States)

    Oethinger, Margret; Warner, Debra K; Schindler, Susan A; Kobayashi, Hideo; Bauer, Thomas W

    2011-04-01

    Intraoperative Gram stains have a reported low sensitivity but high specificity when used to help diagnose periprosthetic infections. In early 2008, we recognized an unexpectedly high frequency of apparent false-positive Gram stains from revision arthroplasties. The purpose of this report is to describe the cause of these false-positive test results. We calculated the sensitivity and specificity of all intraoperative Gram stains submitted from revision arthroplasty cases during a 3-month interval using microbiologic cultures of the same samples as the gold standard. Methods of specimen harvesting, handling, transport, distribution, specimen processing including tissue grinding/macerating, Gram staining, and interpretation were studied. After a test modification, results of specimens were prospectively collected for a second 3-month interval, and the sensitivity and specificity of intraoperative Gram stains were calculated. The retrospective review of 269 Gram stains submitted from revision arthroplasties indicated historic sensitivity and specificity values of 23% and 92%, respectively. Systematic analysis of all steps of the procedure identified Gram-stained but nonviable bacteria in commercial broth reagents used as diluents for maceration of periprosthetic membranes before Gram staining and culture. Polymerase chain reaction and sequencing showed mixed bacterial DNA. Evaluation of 390 specimens after initiating standardized Millipore filtering of diluent fluid revealed a reduced number of positive Gram stains, yielding 9% sensitivity and 99% specificity. Clusters of false-positive Gram stains have been reported in other clinical conditions. They are apparently rare related to diagnosing periprosthetic infections but have severe consequences if used to guide treatment. Even occasional false-positive Gram stains should prompt review of laboratory methods. Our observations implicate dead bacteria in microbiologic reagents as potential sources of false-positive Gram

  2. 40 CFR 300.300 - Phase I-Discovery or notification.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Phase I-Discovery or notification. 300.300 Section 300.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND... person in charge of a vessel or a facility shall, as soon as he or she has knowledge of any discharge...

  3. Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA inhibitors using DNA-encoded library technology.

    Science.gov (United States)

    Soutter, Holly H; Centrella, Paolo; Clark, Matthew A; Cuozzo, John W; Dumelin, Christoph E; Guie, Marie-Aude; Habeshian, Sevan; Keefe, Anthony D; Kennedy, Kaitlyn M; Sigel, Eric A; Troast, Dawn M; Zhang, Ying; Ferguson, Andrew D; Davies, Gareth; Stead, Eleanor R; Breed, Jason; Madhavapeddi, Prashanti; Read, Jon A

    2016-12-06

    Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (10 11 unique small molecules) against multiple forms of the InhA enzyme in a multiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.

  4. Early detection of pharmacovigilance signals with automated methods based on false discovery rates: a comparative study.

    Science.gov (United States)

    Ahmed, Ismaïl; Thiessard, Frantz; Miremont-Salamé, Ghada; Haramburu, Françoise; Kreft-Jais, Carmen; Bégaud, Bernard; Tubert-Bitter, Pascale

    2012-06-01

    Improving the detection of drug safety signals has led several pharmacovigilance regulatory agencies to incorporate automated quantitative methods into their spontaneous reporting management systems. The three largest worldwide pharmacovigilance databases are routinely screened by the lower bound of the 95% confidence interval of proportional reporting ratio (PRR₀₂.₅), the 2.5% quantile of the Information Component (IC₀₂.₅) or the 5% quantile of the Gamma Poisson Shrinker (GPS₀₅). More recently, Bayesian and non-Bayesian False Discovery Rate (FDR)-based methods were proposed that address the arbitrariness of thresholds and allow for a built-in estimate of the FDR. These methods were also shown through simulation studies to be interesting alternatives to the currently used methods. The objective of this work was twofold. Based on an extensive retrospective study, we compared PRR₀₂.₅, GPS₀₅ and IC₀₂.₅ with two FDR-based methods derived from the Fisher's exact test and the GPS model (GPS(pH0) [posterior probability of the null hypothesis H₀ calculated from the Gamma Poisson Shrinker model]). Secondly, restricting the analysis to GPS(pH0), we aimed to evaluate the added value of using automated signal detection tools compared with 'traditional' methods, i.e. non-automated surveillance operated by pharmacovigilance experts. The analysis was performed sequentially, i.e. every month, and retrospectively on the whole French pharmacovigilance database over the period 1 January 1996-1 July 2002. Evaluation was based on a list of 243 reference signals (RSs) corresponding to investigations launched by the French Pharmacovigilance Technical Committee (PhVTC) during the same period. The comparison of detection methods was made on the basis of the number of RSs detected as well as the time to detection. Results comparing the five automated quantitative methods were in favour of GPS(pH0) in terms of both number of detections of true signals and

  5. Using the longest significance run to estimate region-specific p-values in genetic association mapping studies

    Directory of Open Access Journals (Sweden)

    Yang Hsin-Chou

    2008-05-01

    Full Text Available Abstract Background Association testing is a powerful tool for identifying disease susceptibility genes underlying complex diseases. Technological advances have yielded a dramatic increase in the density of available genetic markers, necessitating an increase in the number of association tests required for the analysis of disease susceptibility genes. As such, multiple-tests corrections have become a critical issue. However the conventional statistical corrections on locus-specific multiple tests usually result in lower power as the number of markers increases. Alternatively, we propose here the application of the longest significant run (LSR method to estimate a region-specific p-value to provide an index for the most likely candidate region. Results An advantage of the LSR method relative to procedures based on genotypic data is that only p-value data are needed and hence can be applied extensively to different study designs. In this study the proposed LSR method was compared with commonly used methods such as Bonferroni's method and FDR controlling method. We found that while all methods provide good control over false positive rate, LSR has much better power and false discovery rate. In the authentic analysis on psoriasis and asthma disease data, the LSR method successfully identified important candidate regions and replicated the results of previous association studies. Conclusion The proposed LSR method provides an efficient exploratory tool for the analysis of sequences of dense genetic markers. Our results show that the LSR method has better power and lower false discovery rate comparing with the locus-specific multiple tests.

  6. False positive results occurring in a radioimmunoassay for hepatitis A IgM antibody of the IgM class

    Energy Technology Data Exchange (ETDEWEB)

    Bucens, M R; Pietroboni, G R; Harnett, G B [Virus Lab., Combined Microbiology Service, Queen Elizabeth II Medical Centre, Perth, Western Australia

    1983-12-01

    The diagnosis of hepatitis A infection is usually based on the presence of hepatitis A specific IgM in a single serum sample. The fortuitous observation in one patient that this reactivity was apparently still present 19 mth after her original illness led to the discovery that the ABBOTT HAVAB-M kit method may produce false positive results. A series of patients who had previously had hepatitis A was retested and false positive results were found in 6% of this group. Control groups consisted of patients with other acute and chronic liver disorders and other acute viral diseases. No reactivity was detected in the control sera. Sucrose gradient fractionation revealed that the factor responsible for the false positive results was associated only with serum fractions containing IgA and IgG and that it could be removed by absorption of sera with staphylococcal protein A but not by absorption with streptococcus AR1 or by 2-mercaptoethanol treatment. It was concluded that following hepatitis A infection some patients produce a rheumatoid factor-like substance (not of IgM class) which is cleared from the serum in 2-3 yr. The presence of this factor may lead to a misdiagnosis in patients presenting with jaundice.

  7. 13 CFR 134.407 - Evidence beyond the record and discovery.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Evidence beyond the record and discovery. 134.407 Section 134.407 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF..., the Administrative Law Judge may not admit evidence beyond the written administrative record nor...

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

    Science.gov (United States)

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

    2017-10-01

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

  9. Further Evidence for Nonspecificity of Theory of Mind in Preschoolers: Training and Transferability in the Understanding of False Beliefs and False Signs

    Science.gov (United States)

    Iao, Lai-Sang; Leekam, Susan; Perner, Josef; McConachie, Helen

    2011-01-01

    In a training study, the authors addressed whether or not preschoolers' difficulty with false belief is due to a domain-specific problem with mental states. Following Slaughter's (1998) design, 57 children who failed a false-belief (FB) pretest received two sessions of training on either an FB, false sign (FS), or control task. All children were…

  10. Characterizing the Joint Effect of Diverse Test-Statistic Correlation Structures and Effect Size on False Discovery Rates in a Multiple-Comparison Study of Many Outcome Measures

    Science.gov (United States)

    Feiveson, Alan H.; Ploutz-Snyder, Robert; Fiedler, James

    2011-01-01

    In their 2009 Annals of Statistics paper, Gavrilov, Benjamini, and Sarkar report the results of a simulation assessing the robustness of their adaptive step-down procedure (GBS) for controlling the false discovery rate (FDR) when normally distributed test statistics are serially correlated. In this study we extend the investigation to the case of multiple comparisons involving correlated non-central t-statistics, in particular when several treatments or time periods are being compared to a control in a repeated-measures design with many dependent outcome measures. In addition, we consider several dependence structures other than serial correlation and illustrate how the FDR depends on the interaction between effect size and the type of correlation structure as indexed by Foerstner s distance metric from an identity. The relationship between the correlation matrix R of the original dependent variables and R, the correlation matrix of associated t-statistics is also studied. In general R depends not only on R, but also on sample size and the signed effect sizes for the multiple comparisons.

  11. 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

  12. False Position, Double False Position and Cramer's Rule

    Science.gov (United States)

    Boman, Eugene

    2009-01-01

    We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

  13. Wide-Area Publish/Subscribe Mobile Resource Discovery Based on IPv6 GeoNetworking

    OpenAIRE

    Noguchi, Satoru; Matsuura, Satoshi; Inomata, Atsuo; Fujikawa, Kazutoshi; Sunahara, Hideki

    2013-01-01

    Resource discovery is an essential function for distributed mobile applications integrated in vehicular communication systems. Key requirements of the mobile resource discovery are wide-area geographic-based discovery and scalable resource discovery not only inside a vehicular ad-hoc network but also through the Internet. While a number of resource discovery solutions have been proposed, most of them have focused on specific scale of network. Furthermore, managing a large number of mobile res...

  14. 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...

  15. Volatility Discovery

    DEFF Research Database (Denmark)

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

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

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

    Science.gov (United States)

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

    2017-06-01

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

  17. Analyzing False Memories in Children with Associative Lists Specific for Their Age

    Science.gov (United States)

    Carneiro, Paula; Albuquerque, Pedro; Fernandez, Angel; Esteves, Francisco

    2007-01-01

    Two experiments attempted to resolve previous contradictory findings concerning developmental trends in false memories within the Deese-Roediger-McDermott (DRM) paradigm by using an improved methodology--constructing age-appropriate associative lists. The research also extended the DRM paradigm to preschoolers. Experiment 1 (N = 320) included…

  18. When representations conflict with reality: the preschooler's problem with false beliefs and "false" photographs.

    Science.gov (United States)

    Zaitchik, D

    1990-04-01

    It has been argued that young preschoolers cannot correctly attribute a false belief to a deceived actor (Wimmer & Perner, 1983). Some researchers claim that the problem lies in the child's inadequate epistemology (Chandler & Boyes, 1982; Wellman, 1988); as such, it is specific to the child's theory of mind and no such problem should appear in reasoning about nonmental representations. This prediction is tested below in the "false photograph" task: here an actor takes a photograph of an object in location X; the object is then moved to location Y. Preschool subjects are asked: "In the picture, where is the object?" Results indicate that photographs are no easier to reason about than are beliefs. Manipulations to boost performance on the photograph task proved ineffective. Further, an explanation of the failure as a processing limitation having nothing to do with the representational nature of beliefs or photographs was ruled out. It is argued that young children's failure on the false belief task is not due to an inadequate epistemology (though they may have one) and is symptomatic of a larger problem with representations.

  19. Experimental analysis of the influence of context awareness on service discovery in PNs

    DEFF Research Database (Denmark)

    Olsen, Rasmus Løvenstein; Nickelsen, Anders; Nielsen, Jimmy Jessen

    2006-01-01

    In this paper we present an experimental prototype for context aware service discovery specifically aimed for Personal Networks. In the paper the concept of context aware service discovery, an architecture and the necessary components for performing context aware service discovery in Personal...... Networks is presented. The paper also presents a set of preliminary performance results of context aware service discovery. This is compared to normal service discovery, and as expected context awareness costs in performance....

  20. Robust and Accurate Anomaly Detection in ECG Artifacts Using Time Series Motif Discovery

    Science.gov (United States)

    Sivaraks, Haemwaan

    2015-01-01

    Electrocardiogram (ECG) anomaly detection is an important technique for detecting dissimilar heartbeats which helps identify abnormal ECGs before the diagnosis process. Currently available ECG anomaly detection methods, ranging from academic research to commercial ECG machines, still suffer from a high false alarm rate because these methods are not able to differentiate ECG artifacts from real ECG signal, especially, in ECG artifacts that are similar to ECG signals in terms of shape and/or frequency. The problem leads to high vigilance for physicians and misinterpretation risk for nonspecialists. Therefore, this work proposes a novel anomaly detection technique that is highly robust and accurate in the presence of ECG artifacts which can effectively reduce the false alarm rate. Expert knowledge from cardiologists and motif discovery technique is utilized in our design. In addition, every step of the algorithm conforms to the interpretation of cardiologists. Our method can be utilized to both single-lead ECGs and multilead ECGs. Our experiment results on real ECG datasets are interpreted and evaluated by cardiologists. Our proposed algorithm can mostly achieve 100% of accuracy on detection (AoD), sensitivity, specificity, and positive predictive value with 0% false alarm rate. The results demonstrate that our proposed method is highly accurate and robust to artifacts, compared with competitive anomaly detection methods. PMID:25688284

  1. Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies

    Directory of Open Access Journals (Sweden)

    Katherine E. Harris

    2018-04-01

    Full Text Available We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1. This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

  2. 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.

  3. 16 CFR 5.61 - Prehearing procedures; motions; interlocutory appeals; summary decision; discovery; compulsory...

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Prehearing procedures; motions; interlocutory appeals; summary decision; discovery; compulsory process. 5.61 Section 5.61 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE STANDARDS OF CONDUCT Disciplinary...

  4. False Advertising

    OpenAIRE

    Rhodes, Andrew; Wilson, Chris M

    2016-01-01

    There is widespread evidence that some firms use false advertising to overstate the value of their products. We consider a model in which a policymaker is able to punish such false claims. We characterize an equilibrium where false advertising actively influences rational buyers, and analyze the effects of policy under different welfare objectives. We establish precise conditions where policy optimally permits a positive level of false advertising, and show how these conditions vary intuitive...

  5. 13 CFR 134.711 - Will the Judge permit discovery and oral hearings?

    Science.gov (United States)

    2010-01-01

    ... Appeals From Women-Owned Small Business Concern (WOSB) and Economically Disadvantaged WOSB Concern (EDWOSB... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Will the Judge permit discovery and oral hearings? 134.711 Section 134.711 Business Credit and Assistance SMALL BUSINESS...

  6. False Belief and Language Comprehension in Cantonese-Speaking Children

    Science.gov (United States)

    Cheung, Him

    2006-01-01

    The current research compared two accounts of the relation between language and false belief in children, namely that (a) language is generally related to false belief because both require secondary representation in a social-interactional context and that (b) specific language structures that explicitly code meta representation contribute…

  7. False belief understanding in Cantonese-speaking children.

    Science.gov (United States)

    Tardif, Twila; Wellman, Henry M; Cheung, Kar Man

    2004-11-01

    The present study investigates the performance of 96 Cantonese-speaking three- to five-year-old preschoolers on three false belief tasks - a deceptive object, a change of location, and an unexpected contents task encompassing a variety of task factors. Most importantly, the research examines the possibility that false belief performance depends on specific linguistic factors such as the type of verb used in the test question--an explicitly false vs. a neutral belief verb. Cantonese was chosen as particularly useful for examining this question because it explicitly codes belief status as either neutral (nam5) or false (ji5wai4), and because it offers additional linguistic and cultural contrasts to research conducted on false belief with children learning English and other Indo-European languages. As expected, a strong age effect was found, as well as a significant advantage for children who received the explicit false belief (ji5wai4) wording and for those who were asked to explain rather than predict the protagonist's actions. Interestingly, there was also a strong task difference with children performing better on the deceptive object task than on the other two false belief tasks. We argue that these results point both to universal trajectories in theory of mind development and to interesting, but localized, effects of language and culture on children's false belief understanding.

  8. Secure Service Discovery in Home Networks

    NARCIS (Netherlands)

    Scholten, Johan; van Dijk, H.W.; De Cock, Danny; Preneel, Bart; Kung, Antonio; d'Hooge, Michel

    2006-01-01

    This paper presents an architecture for secure service discovery for use in home networks. We give an overview and rationale of a cluster-based home network architecture that bridges different, often vendor specific, network technologies. We show how it integrates security, communication, and

  9. Implementing web-scale discovery services a practical guide for librarians

    CERN Document Server

    Thompson, JoLinda

    2014-01-01

    Implementing Web-Scale Discovery Services: A Practical Guide for Librarians is a source for librarians seeking to evaluate, purchase, and implement a web-scale discovery service. The book breaks down each phase of the project into decision points and action plans to help librarians select and implement a system that meets their specific needs.

  10. Polar Domain Discovery with Sparkler

    Science.gov (United States)

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

    2017-12-01

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

  11. Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening

    Directory of Open Access Journals (Sweden)

    Tokudome S

    2016-05-01

    Full Text Available Shinkan Tokudome,1 Ryosuke Ando,2 Yoshiro Koda,3 1Department of Nutritional Epidemiology, National Institute of Health and Nutrition, Shinjuku-ku, Tokyo, 2Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, 3Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, Kurume, Japan Abstract: The discoveries and application of prostate-specific antigen (PSA have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (~30%. There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC and the US Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1 adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2 improving test performance using doubling time, density, and ratio of free: total PSA; and 3 fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1 examinations of cell proliferation and cell cycle markers

  12. Differentiating true and false schematic memories in older adults.

    Science.gov (United States)

    Webb, Christina E; Dennis, Nancy A

    2018-02-06

    While schemas aid memory for schematically related information, the gist induced by the schema can also lead to high rates of false memories, especially in older adults. The neural mechanisms that support and differentiate true and false memories in aging are not well understood. The current study sought to clarify this, using a novel scene paradigm to investigate the role of schemas on true and false memories in older adults. Healthy older adults encoded schematic scenes (e.g., bathroom). At retrieval, participants were tested on their memory for both schematic and non-schematic targets and lures while fMRI data was collected. Results indicate that true memories were supported by the typical retrieval network, and activity in this network was greater for true than false memories. Schema specific retrieval was supported by mPFC, extending this common finding to aging. While no region differentiated false memories compared to correct rejections, results showed that individual differences in false memory rates were associated with variability in neural activity. The findings underscore the importance of elucidating the neural basis of cognition within older adults, as well as the specific contribution of individual differences to the neural basis of memory errors in aging. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

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

    2012-06-01

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

  14. BayesMotif: de novo protein sorting motif discovery from impure datasets.

    Science.gov (United States)

    Hu, Jianjun; Zhang, Fan

    2010-01-18

    Protein sorting is the process that newly synthesized proteins are transported to their target locations within or outside of the cell. This process is precisely regulated by protein sorting signals in different forms. A major category of sorting signals are amino acid sub-sequences usually located at the N-terminals or C-terminals of protein sequences. Genome-wide experimental identification of protein sorting signals is extremely time-consuming and costly. Effective computational algorithms for de novo discovery of protein sorting signals is needed to improve the understanding of protein sorting mechanisms. We formulated the protein sorting motif discovery problem as a classification problem and proposed a Bayesian classifier based algorithm (BayesMotif) for de novo identification of a common type of protein sorting motifs in which a highly conserved anchor is present along with a less conserved motif regions. A false positive removal procedure is developed to iteratively remove sequences that are unlikely to contain true motifs so that the algorithm can identify motifs from impure input sequences. Experiments on both implanted motif datasets and real-world datasets showed that the enhanced BayesMotif algorithm can identify anchored sorting motifs from pure or impure protein sequence dataset. It also shows that the false positive removal procedure can help to identify true motifs even when there is only 20% of the input sequences containing true motif instances. We proposed BayesMotif, a novel Bayesian classification based algorithm for de novo discovery of a special category of anchored protein sorting motifs from impure datasets. Compared to conventional motif discovery algorithms such as MEME, our algorithm can find less-conserved motifs with short highly conserved anchors. Our algorithm also has the advantage of easy incorporation of additional meta-sequence features such as hydrophobicity or charge of the motifs which may help to overcome the limitations of

  15. NASA Reverb: Standards-Driven Earth Science Data and Service Discovery

    Science.gov (United States)

    Cechini, M. F.; Mitchell, A.; Pilone, D.

    2011-12-01

    NASA's Earth Observing System Data and Information System (EOSDIS) is a core capability in NASA's Earth Science Data Systems Program. NASA's EOS ClearingHOuse (ECHO) is a metadata catalog for the EOSDIS, providing a centralized catalog of data products and registry of related data services. Working closely with the EOSDIS community, the ECHO team identified a need to develop the next generation EOS data and service discovery tool. This development effort relied on the following principles: + Metadata Driven User Interface - Users should be presented with data and service discovery capabilities based on dynamic processing of metadata describing the targeted data. + Integrated Data & Service Discovery - Users should be able to discovery data and associated data services that facilitate their research objectives. + Leverage Common Standards - Users should be able to discover and invoke services that utilize common interface standards. Metadata plays a vital role facilitating data discovery and access. As data providers enhance their metadata, more advanced search capabilities become available enriching a user's search experience. Maturing metadata formats such as ISO 19115 provide the necessary depth of metadata that facilitates advanced data discovery capabilities. Data discovery and access is not limited to simply the retrieval of data granules, but is growing into the more complex discovery of data services. These services include, but are not limited to, services facilitating additional data discovery, subsetting, reformatting, and re-projecting. The discovery and invocation of these data services is made significantly simpler through the use of consistent and interoperable standards. By utilizing an adopted standard, developing standard-specific adapters can be utilized to communicate with multiple services implementing a specific protocol. The emergence of metadata standards such as ISO 19119 plays a similarly important role in discovery as the 19115 standard

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

    Science.gov (United States)

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

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

  17. Acute effects of triazolam on false recognition.

    Science.gov (United States)

    Mintzer, M Z; Griffiths, R R

    2000-12-01

    Neuropsychological, neuroimaging, and electrophysiological techniques have been applied to the study of false recognition; however, psychopharmacological techniques have not been applied. Benzodiazepine sedative/anxiolytic drugs produce memory deficits similar to those observed in organic amnesia and may be useful tools for studying normal and abnormal memory mechanisms. The present double-blind, placebo-controlled repeated measures study examined the acute effects of orally administered triazolam (Halcion; 0.125 and 0.25 mg/70 kg), a benzodiazepine hypnotic, on performance in the Deese (1959)/Roediger-McDermott (1995) false recognition paradigm in 24 healthy volunteers. Paralleling previous demonstrations in amnesic patients, triazolam produced significant dose-related reductions in false recognition rates to nonstudied words associatively related to studied words, suggesting that false recognition relies on normal memory mechanisms impaired in benzodiazepine-induced amnesia. The results also suggested that relative to placebo, triazolam reduced participants' reliance on memory for item-specific versus list-common semantic information and reduced participants' use of remember versus know responses.

  18. Use of allosteric targets in the discovery of safer drugs.

    Science.gov (United States)

    Grover, Ashok Kumar

    2013-01-01

    The need for drugs with fewer side effects cannot be overemphasized. Today, most drugs modify the actions of enzymes, receptors, transporters and other molecules by directly binding to their active (orthosteric) sites. However, orthosteric site configuration is similar in several proteins performing related functions and this leads to a lower specificity of a drug for the desired protein. Consequently, such drugs may have adverse side effects. A new basis of drug discovery is emerging based on the binding of the drug molecules to sites away (allosteric) from the orthosteric sites. It is possible to find allosteric sites which are unique and hence more specific as targets for drug discovery. Of many available examples, two are highlighted here. The first is caloxins - a new class of highly specific inhibitors of plasma membrane Ca²⁺ pumps. The second concerns the modulation of receptors for the neurotransmitter acetylcholine, which binds to 12 types of receptors. Exploitation of allosteric sites has led to the discovery of drugs which can selectively modulate the activation of only 1 (M1 muscarinic) out of the 12 different types of acetylcholine receptors. These drugs are being tested for schizophrenia treatment. It is anticipated that the drug discovery exploiting allosteric sites will lead to more effective therapeutic agents with fewer side effects. Copyright © 2013 S. Karger AG, Basel.

  19. Acetaminophen/paracetamol: A history of errors, failures and false decisions.

    Science.gov (United States)

    Brune, K; Renner, B; Tiegs, G

    2015-08-01

    Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existed to renowned researchers having contributed to the medical use of paracetamol and its precursors as H.U. Zollinger, S. Moeschlin, U. Dubach, J. Axelrod and others. Further information is found in earlier reviews by Eichengrün, Rodnan and Benedek, Sneader, Brune; comp. references. The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side-effect 'epidemy' (phenacetin nephropathy, drug-induced interstitial nephritis) and ends with the discovery of second-generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound. © 2014 European Pain Federation - EFIC®

  20. Blueprint for antimicrobial hit discovery targeting metabolic networks.

    Science.gov (United States)

    Shen, Y; Liu, J; Estiu, G; Isin, B; Ahn, Y-Y; Lee, D-S; Barabási, A-L; Kapatral, V; Wiest, O; Oltvai, Z N

    2010-01-19

    Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy.

  1. Working memory affects false memory production for emotional events.

    Science.gov (United States)

    Mirandola, Chiara; Toffalini, Enrico; Ciriello, Alfonso; Cornoldi, Cesare

    2017-01-01

    Whereas a link between working memory (WM) and memory distortions has been demonstrated, its influence on emotional false memories is unclear. In two experiments, a verbal WM task and a false memory paradigm for negative, positive or neutral events were employed. In Experiment 1, we investigated individual differences in verbal WM and found that the interaction between valence and WM predicted false recognition, with negative and positive material protecting high WM individuals against false remembering; the beneficial effect of negative material disappeared in low WM participants. In Experiment 2, we lowered the WM capacity of half of the participants with a double task request, which led to an overall increase in false memories; furthermore, consistent with Experiment 1, the increase in negative false memories was larger than that of neutral or positive ones. It is concluded that WM plays a critical role in determining false memory production, specifically influencing the processing of negative material.

  2. Mental Rotation in False Belief Understanding.

    Science.gov (United States)

    Xie, Jiushu; Cheung, Him; Shen, Manqiong; Wang, Ruiming

    2018-05-01

    This study examines the spontaneous use of embodied egocentric transformation (EET) in understanding false beliefs in the minds of others. EET involves the participants mentally transforming or rotating themselves into the orientation of an agent when trying to adopt his or her visuospatial perspective. We argue that psychological perspective taking such as false belief reasoning may also involve EET because of what has been widely reported in the embodied cognition literature, showing that our processing of abstract, propositional information is often grounded in concrete bodily sensations which are not apparently linked to higher cognition. In Experiment 1, an agent placed a ball into one of two boxes and left. The ball then rolled out and moved either into the other box (new box) or back into the original one (old box). The participants were to decide from which box they themselves or the agent would try to recover the ball. Results showed that false belief performance was affected by increased orientation disparity between the participants and the agent, suggesting involvement of embodied transformation. In Experiment 2, false belief was similarly induced and the participants were to decide if the agent would try to recover the ball in one specific box. Orientation disparity was again found to affect false belief performance. The present results extend previous findings on EET in visuospatial perspective taking and suggest that false belief reasoning, which is a kind of psychological perspective taking, can also involve embodied rotation, consistent with the embodied cognition view. Copyright © 2018 Cognitive Science Society, Inc.

  3. Improved estimation of the noncentrality parameter distribution from a large number of t-statistics, with applications to false discovery rate estimation in microarray data analysis.

    Science.gov (United States)

    Qu, Long; Nettleton, Dan; Dekkers, Jack C M

    2012-12-01

    Given a large number of t-statistics, we consider the problem of approximating the distribution of noncentrality parameters (NCPs) by a continuous density. This problem is closely related to the control of false discovery rates (FDR) in massive hypothesis testing applications, e.g., microarray gene expression analysis. Our methodology is similar to, but improves upon, the existing approach by Ruppert, Nettleton, and Hwang (2007, Biometrics, 63, 483-495). We provide parametric, nonparametric, and semiparametric estimators for the distribution of NCPs, as well as estimates of the FDR and local FDR. In the parametric situation, we assume that the NCPs follow a distribution that leads to an analytically available marginal distribution for the test statistics. In the nonparametric situation, we use convex combinations of basis density functions to estimate the density of the NCPs. A sequential quadratic programming procedure is developed to maximize the penalized likelihood. The smoothing parameter is selected with the approximate network information criterion. A semiparametric estimator is also developed to combine both parametric and nonparametric fits. Simulations show that, under a variety of situations, our density estimates are closer to the underlying truth and our FDR estimates are improved compared with alternative methods. Data-based simulations and the analyses of two microarray datasets are used to evaluate the performance in realistic situations. © 2012, The International Biometric Society.

  4. Reducing false asystole alarms in intensive care.

    Science.gov (United States)

    Dekimpe, Remi; Heldt, Thomas

    2017-07-01

    High rates of false monitoring alarms in intensive care can desensitize staff and therefore pose a significant risk to patient safety. Like other critical arrhythmia alarms, asystole alarms require immediate attention by the care providers as a true asystole event can be acutely life threatening. Here, it is illustrated that most false asystole alarms can be attributed to poor signal quality, and we propose and evaluate an algorithm to identify data windows of poor signal quality and thereby help suppress false asystole alarms. The algorithm combines intuitive signal-quality features (degree of signal saturation and baseline wander) and information from other physiological signals that might be available. Algorithm training and testing was performed on the MIMIC II and 2015 PhysioNet/Computing in Cardiology Challenge databases, respectively. The algorithm achieved an alarm specificity of 81.0% and sensitivity of 95.4%, missing only one out of 22 true asystole alarms. On a separate neonatal data set, the algorithm was able to reject 89.7% (890 out of 992) of false asystole alarms while keeping all 22 true events. The results show that the false asystole alarm rate can be significantly reduced through basic signal quality evaluation.

  5. Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations.

    Science.gov (United States)

    Feusier, Julie; Witherspoon, David J; Scott Watkins, W; Goubert, Clément; Sasani, Thomas A; Jorde, Lynn B

    2017-01-01

    Polymorphic human Alu elements are excellent tools for assessing population structure, and new retrotransposition events can contribute to disease. Next-generation sequencing has greatly increased the potential to discover Alu elements in human populations, and various sequencing and bioinformatics methods have been designed to tackle the problem of detecting these highly repetitive elements. However, current techniques for Alu discovery may miss rare, polymorphic Alu elements. Combining multiple discovery approaches may provide a better profile of the polymorphic Alu mobilome. Alu Yb8/9 elements have been a focus of our recent studies as they are young subfamilies (~2.3 million years old) that contribute ~30% of recent polymorphic Alu retrotransposition events. Here, we update our ME-Scan methods for detecting Alu elements and apply these methods to discover new insertions in a large set of individuals with diverse ancestral backgrounds. We identified 5,288 putative Alu insertion events, including several hundred novel Alu Yb8/9 elements from 213 individuals from 18 diverse human populations. Hundreds of these loci were specific to continental populations, and 23 non-reference population-specific loci were validated by PCR. We provide high-quality sequence information for 68 rare Alu Yb8/9 elements, of which 11 have hallmarks of an active source element. Our subfamily distribution of rare Alu Yb8/9 elements is consistent with previous datasets, and may be representative of rare loci. We also find that while ME-Scan and low-coverage, whole-genome sequencing (WGS) detect different Alu elements in 41 1000 Genomes individuals, the two methods yield similar population structure results. Current in-silico methods for Alu discovery may miss rare, polymorphic Alu elements. Therefore, using multiple techniques can provide a more accurate profile of Alu elements in individuals and populations. We improved our false-negative rate as an indicator of sample quality for future

  6. Topology Discovery Using Cisco Discovery Protocol

    OpenAIRE

    Rodriguez, Sergio R.

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  8. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

    DEFF Research Database (Denmark)

    Vrijens, Karen; Winckelmans, Ellen; Tsamou, Maria

    2017-01-01

    Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. Methods: Microarray analyses were performed in 98...... healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women...

  9. Improving the quality of biomarker discovery research: the right samples and enough of them.

    Science.gov (United States)

    Pepe, Margaret S; Li, Christopher I; Feng, Ziding

    2015-06-01

    Biomarker discovery research has yielded few biomarkers that validate for clinical use. A contributing factor may be poor study designs. The goal in discovery research is to identify a subset of potentially useful markers from a large set of candidates assayed on case and control samples. We recommend the PRoBE design for selecting samples. We propose sample size calculations that require specifying: (i) a definition for biomarker performance; (ii) the proportion of useful markers the study should identify (Discovery Power); and (iii) the tolerable number of useless markers amongst those identified (False Leads Expected, FLE). We apply the methodology to a study of 9,000 candidate biomarkers for risk of colon cancer recurrence where a useful biomarker has positive predictive value ≥ 30%. We find that 40 patients with recurrence and 160 without recurrence suffice to filter out 98% of useless markers (2% FLE) while identifying 95% of useful biomarkers (95% Discovery Power). Alternative methods for sample size calculation required more assumptions. Biomarker discovery research should utilize quality biospecimen repositories and include sample sizes that enable markers meeting prespecified performance characteristics for well-defined clinical applications to be identified. The scientific rigor of discovery research should be improved. ©2015 American Association for Cancer Research.

  10. Applying Hierarchical Task Analysis Method to Discovery Layer Evaluation

    Directory of Open Access Journals (Sweden)

    Marlen Promann

    2015-03-01

    Full Text Available Libraries are implementing discovery layers to offer better user experiences. While usability tests have been helpful in evaluating the success or failure of implementing discovery layers in the library context, the focus has remained on its relative interface benefits over the traditional federated search. The informal site- and context specific usability tests have offered little to test the rigor of the discovery layers against the user goals, motivations and workflow they have been designed to support. This study proposes hierarchical task analysis (HTA as an important complementary evaluation method to usability testing of discovery layers. Relevant literature is reviewed for the discovery layers and the HTA method. As no previous application of HTA to the evaluation of discovery layers was found, this paper presents the application of HTA as an expert based and workflow centered (e.g. retrieving a relevant book or a journal article method to evaluating discovery layers. Purdue University’s Primo by Ex Libris was used to map eleven use cases as HTA charts. Nielsen’s Goal Composition theory was used as an analytical framework to evaluate the goal carts from two perspectives: a users’ physical interactions (i.e. clicks, and b user’s cognitive steps (i.e. decision points for what to do next. A brief comparison of HTA and usability test findings is offered as a way of conclusion.

  11. Recall of false memories in individuals scoring high in schizotypy: memory distortions are scale specific.

    Science.gov (United States)

    Saunders, Jo; Randell, Jordan; Reed, Phil

    2012-06-01

    Previous research has indicated abnormal semantic activation in individuals scoring higher in schizotypy. In the current experiment, semantic activation was examined by using the Deese-Roediger-McDermott paradigm of false memories. Participants were assessed for schizotypy using the Oxford-Liverpool Inventory of Feelings (OLIFE). Participants studied lists of semantically related words in which a critical and highly associated word was absent. Participants then recalled the list. Participants high in Unusual Experiences and Cognitive Disorganization recalled more critical non-presented words, weakly related studied words, and fewer studied words than participants who scored low on these measures. Previous research using the cognitive-perceptual factor of the Schizotypy Personality Questionnaire found reduced false memories, while the Unusual Experiences subscale of the OLIFE was associated with more false memories. Both scales cover similar unusual perceptual experiences and it is unclear why they led to divergent results. The findings suggest that subtypes of schizotypy are associated with abnormal semantic activation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Improving sensitivity of linear regression-based cell type-specific differential expression deconvolution with per-gene vs. global significance threshold.

    Science.gov (United States)

    Glass, Edmund R; Dozmorov, Mikhail G

    2016-10-06

    The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts hidden in high-dimensional gene expression data that may negatively affect linear regression. In this paper we quantify the parameter space affecting the performance of linear regression (sensitivity of cell type-specific differential expression detection) on a per-gene basis. We evaluated the effect of sample sizes, cell type-specific proportion variability, and mean squared error on sensitivity of cell type-specific differential expression detection using linear regression. Each parameter affected variability of cell type-specific expression estimates and, subsequently, the sensitivity of differential expression detection. We provide the R package, LRCDE, which performs linear regression-based cell type-specific differential expression (deconvolution) detection on a gene-by-gene basis. Accounting for variability around cell type-specific gene expression estimates, it computes per-gene t-statistics of differential detection, p-values, t-statistic-based sensitivity, group-specific mean squared error, and several gene-specific diagnostic metrics. The sensitivity of linear regression-based cell type-specific differential expression detection differed for each gene as a function of mean squared error, per group sample sizes, and variability of the proportions

  13. Discovery as a process

    Energy Technology Data Exchange (ETDEWEB)

    Loehle, C.

    1994-05-01

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

  14. The risk factor of false-negative and false-positive for T-SPOT.TB in active tuberculosis.

    Science.gov (United States)

    Di, Li; Li, Yan

    2018-02-01

    T-SPOT.TB is a promising diagnosis tool to identify both pulmonary tuberculosis and extrapulmonary tuberculosis, as well as latent tuberculosis; however, the factors that affect the results of T-SPOT.TB remains unclear. In this study, we aim to figure out the risk factor of T-SPOT.TB for active TB. A total of 349 patients were recruited between January 1st, 2016 and January 22st, 2017 at Renmin Hospital of Wuhan University, including 98 subjects with TB and 251 subjects with non-TB disease, and received T-SPOT.TB (Oxford Immunotec Ltd). Statistics were analyzed by SPSS 19.0 using logistic regression. The overall specificity and sensitivity of the T-SPOT.TB was 92.83% (233/251; 95%CI 0.8872-0.9557) and 83.67% (82/98; 95%CI 0.7454-0.9010), respectively. Patients with tuberculous meningitis were more likely to have false-negative results (OR 17.4, 95%CI 3.068-98.671; P.05). Tuberculous meningitis was a risk factor of false-negative for T-SPOT.TB, while cured TB was a risk factor of false-positive. © 2017 Wiley Periodicals, Inc.

  15. Higgs Discovery

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2013-01-01

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

  16. Comparison of discovery limits for extra Z bosons at future colliders

    International Nuclear Information System (INIS)

    Godfrey, S.

    1995-01-01

    We study and compare the discovery potential for heavy neutral gauge bosons (Z') at various e + e - and pp (-) colliders that are planned or have been proposed. Typical discovery limits are for the Fermilab Tevatron ∼1 TeV, Di-Tevatron ∼2 TeV, CERN LHC ∼4 TeV, LSGNA (a 60 TeV pp collider) ∼13 TeV while the e + e - discovery limits are 2--10x √s with the large variation reflecting the model dependence of the limits. While both types of colliders have comparable discovery limits the hadron colliders are generally less dependent on the specific Z' model and provide more robust limits since the signal has little background. In contrast, discovery limits for e + e - limits are more model dependent and, because they are based on indirect inferences of deviations from standard model predictions, they are more sensitive to systematic errors

  17. Neuroscience-driven discovery and development of sleep therapeutics

    NARCIS (Netherlands)

    Dresler, M.; Spoormaker, V.I.; Beitinger, P.; Czisch, M.; Kimura, M.; Steiger, A.; Holsboer, F.

    2014-01-01

    Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite the fact that disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological,

  18. 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.

  19. False-negative diffusion-weighted imaging findings in acute stroke

    International Nuclear Information System (INIS)

    Ishikawa, Tatsuya; Yuasa, Naoki; Otomo, Takashi; Shiramizu, Hideki; Matsuda, Hiroshi; Kitagawa, Yasuhisa; Takagi, Shigeharu

    2006-01-01

    The utility of DWI (diffusion-weighted imaging) has been established in acute ischemic stroke. However, some patients with acute stroke show no abnormal signals on DWI, despite the presence of infarction (false-negative DWI). We analyzed the relationship between false-negative DWI and the clinical manifestations of acute ischemic stroke in 151 DWI-positive (89%) and 19 false-negative DWI (11%) patients. We performed MRI within 24 hours after onset at our hospital. Non-specific clinical manifestations, including vertigo and nausea, were frequently observed in false-negative DWI patients. As regards the vascular territory, false-negative DWI was noted in 15.3% of 59 patients with infarctions within the territory of the vertebrobasilar artery. Concerning the duration from onset to initial imaging, 73.7% of the patients with false-negative DWI findings underwent MRI examination within 6 hours after onset. Of the patients with false-negative DWI, 84.2% had lacunar infarction (χ 2 =16.4, P<0.001). In conclusion, false negative DWI is more frequently observed in lacunar infarction than in atherothrombotic infarction or cardiogenic embolism. It is important to examine carefully the neurological changes occurring in patients who present with acute stroke, but have negative DWI findings. (author)

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

    Science.gov (United States)

    Scerri, Eric

    2015-03-13

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

  1. When are false-positive and false-negative 18F'FDG PET scans really false?

    International Nuclear Information System (INIS)

    Binns, D.S.; Hicks, R.J.; Fawcett, M.E.

    1999-01-01

    Full text: A 61-year-old male presented with locally advanced squamous cell carcinoma of the base of tongue. In the absence of wider metastatic disease on conventional staging, he was enrolled in a phase I, dose escalation chemoradiotherapy trial. In this study, therapeutic response to radiotherapy combined with cisplatin and a chemotherapeutic agent which specifically targets hypoxic cells (tirapazamine) was evaluated with serial 18 F-FDG PET scans. Baseline 18 F-FDG PET confirmed locally advanced disease, although a previously undetected lower cervical lymph node was identified and included in the radiotherapy portal. Whole-body PET revealed a small metabolically active area adjacent to the right hemidiaphragm. Respiratory gated, high-resolution helical CT failed to find structural evidence of disease and, as a result, the patient was enrolled in the 7 week therapy regime on the assumption that the PET finding was a false-positive result. Repeat 18 F-FDG PET scans at the middle, end and 12 weeks post-treatment showed excellent therapeutic response in the head and neck which was discordant with clinical and CT findings, and resolution of the metabolically active chest lesion. Despite the negative PET scan, persistent clinical and CT evidence of a residual tumour mass suggested a false-negative result and resulted in a neck lymph node dissection. This showed no evidence of malignant cells. Five months following treatment, the patient presented with pleural effusion at the base on the right lung. Subsequent CT scanning showed a small pleural lesion at the site of initial 18 F-FDG uptake. Biopsy confirmed metastatic disease. The apparent transient resolution of 18 F-FDG uptake in the pleural lesion with treatment presumably reflected a combination of reduced metabolic activity and size due to the partial, but not complete, cytotoxic effects of cisplatin. In conclusion, this case emphasizes the importance of pathological review and clinical follow-up in reconciling

  2. Beyond Discovery

    DEFF Research Database (Denmark)

    Korsgaard, Steffen; Sassmannshausen, Sean Patrick

    2017-01-01

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

  3. False memories, but not false beliefs, affect implicit attitudes for food preferences.

    Science.gov (United States)

    Howe, David; Anderson, Rachel J; Dewhurst, Stephen A

    2017-09-01

    Previous studies have found that false memories and false beliefs of childhood experiences can have attitudinal consequences. Previous studies have, however, focused exclusively on explicit attitude measures without exploring whether implicit attitudes are similarly affected. Using a false feedback/imagination inflation paradigm, false memories and beliefs of enjoying a certain food as a child were elicited in participants, and their effects were assessed using both explicit attitude measures (self-report questionnaires) and implicit measures (a Single-Target Implicit Association Test). Positive changes in explicit attitudes were observed both in participants with false memories and participants with false beliefs. In contrast, only participants with false memories exhibited more positive implicit attitudes. The findings are discussed in terms of theories of explicit and implicit attitudes. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Characterization of binding specificities of bovine leucocyte class I molecules: impacts for rational epitope discovery

    DEFF Research Database (Denmark)

    Hansen, Andreas M.; Rasmussen, Michael; Svitek, Nicholas

    2014-01-01

    confirmed experimentally. This study demonstrates how biochemical high-throughput assays combined with immunoinformatics can be used to characterize the peptide-binding motifs of BoLA-I molecules, boosting performance of MHC peptide-binding prediction methods, and empowering rational epitope discovery...

  5. Reconstructing Sessions from Data Discovery and Access Logs to Build a Semantic Knowledge Base for Improving Data Discovery

    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.

  6. "Eureka, Eureka!" Discoveries in Science

    Science.gov (United States)

    Agarwal, Pankaj

    2011-01-01

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

  7. Transient medial prefrontal perturbation reduces false memory formation

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Linden, M.H. van der; Almeida, R.F. de; Müller, N.C.J.; Bovy, L.; Dresler, M.; Morris, R.G.M.; Fernandez, G.S.E.

    2017-01-01

    Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott

  8. Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

    Science.gov (United States)

    Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

    2018-06-05

    Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

  9. Chemical Discovery

    Science.gov (United States)

    Brown, Herbert C.

    1974-01-01

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

  10. The Discovery of Arthropod-Specific Viruses in Hematophagous Arthropods: An Open Door to Understanding the Mechanisms of Arbovirus and Arthropod Evolution?

    Science.gov (United States)

    Calisher, Charles H; Higgs, Stephen

    2018-01-07

    The discovery of an odd virus from hematophagous arthropods 40 years ago by Stollar and Thomas described cell fusing agent virus in cells derived from Aedes aegypti mosquitoes. Then came the report of Kamiti River virus from Ae. macintoshi in 1999, followed by worldwide reports of the discovery of other viruses of mosquitoes, ticks, and midges that replicate only in arthropods and not in vertebrates or in vertebrate cells. These viruses (now totaling at least 64 published) have genomes analogous to viruses in various families that include arboviruses and nonarboviruses. It is likely that some of these viruses have been insufficiently studied and may yet be shown to infect vertebrates. However, there is no doubt that the vast majority are restricted to arthropods alone and that they represent a recently recognized clade. Their biology, modes of transmission, worldwide distribution (some have been detected in wild-caught mosquitoes in both Asia and the United States, for example), molecular characteristics of their genomes, and potential for becoming vertebrate pathogens, or at least serving as virus reservoirs, are fascinating and may provide evidence useful in understanding virus evolution. Because metagenomics studies of arthropods have shown that arthropod genomes are the sources of arthropod virus genomes, further studies may also provide insights into the evolution of arthropods. More recently, others have published excellent papers that briefly review discoveries of arthropod viruses and that characterize certain genomic peculiarities, but, to now, there have been no reviews that encompass all these facets. We therefore anticipate that this review is published at a time and in a manner that is helpful for both virologists and entomologists to make more sense and understanding of this recently recognized and obviously important virus group. This review focuses specifically on arthropod viruses in hematophagous arthropods.

  11. False Positive and False Negative Effects on Network Attacks

    Science.gov (United States)

    Shang, Yilun

    2018-01-01

    Robustness against attacks serves as evidence for complex network structures and failure mechanisms that lie behind them. Most often, due to detection capability limitation or good disguises, attacks on networks are subject to false positives and false negatives, meaning that functional nodes may be falsely regarded as compromised by the attacker and vice versa. In this work, we initiate a study of false positive/negative effects on network robustness against three fundamental types of attack strategies, namely, random attacks (RA), localized attacks (LA), and targeted attack (TA). By developing a general mathematical framework based upon the percolation model, we investigate analytically and by numerical simulations of attack robustness with false positive/negative rate (FPR/FNR) on three benchmark models including Erdős-Rényi (ER) networks, random regular (RR) networks, and scale-free (SF) networks. We show that ER networks are equivalently robust against RA and LA only when FPR equals zero or the initial network is intact. We find several interesting crossovers in RR and SF networks when FPR is taken into consideration. By defining the cost of attack, we observe diminishing marginal attack efficiency for RA, LA, and TA. Our finding highlights the potential risk of underestimating or ignoring FPR in understanding attack robustness. The results may provide insights into ways of enhancing robustness of network architecture and improve the level of protection of critical infrastructures.

  12. 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.

  13. Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method.

    Science.gov (United States)

    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.

  14. Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2017-11-08

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

  16. Affect influences false memories at encoding: evidence from recognition data.

    Science.gov (United States)

    Storbeck, Justin; Clore, Gerald L

    2011-08-01

    Memory is susceptible to illusions in the form of false memories. Prior research found, however, that sad moods reduce false memories. The current experiment had two goals: (1) to determine whether affect influences retrieval processes, and (2) to determine whether affect influences the strength and the persistence of false memories. Happy or sad moods were induced either before or after learning word lists designed to produce false memories. Control groups did not experience a mood induction. We found that sad moods reduced false memories only when induced before learning. Signal detection analyses confirmed that sad moods induced prior to learning reduced activation of nonpresented critical lures suggesting that they came to mind less often. Affective states, however, did not influence retrieval effects. We conclude that negative affective states promote item-specific processing, which reduces false memories in a similar way as using an explicitly guided cognitive control strategy. 2011 APA, all rights reserved

  17. Semantic distributed resource discovery for multiple resource providers

    NARCIS (Netherlands)

    Pittaras, C.; Ghijsen, M.; Wibisono, A.; Grosso, P.; van der Ham, J.; de Laat, C.

    2012-01-01

    An emerging modus operandi among providers of cloud infrastructures is the one where they share and combine their heterogenous resources to offer end user services tailored to specific scientific and business needs. A challenge to overcome is the discovery of suitable resources among these multiple

  18. False memories and confabulation.

    Science.gov (United States)

    Johnson, M K; Raye, C L

    1998-04-01

    Memory distortions range from the benign (thinking you mailed a check that you only thought about mailing), to the serious (confusing what you heard after a crime with what you actually saw), to the fantastic (claiming you piloted a spaceship). We review theoretical ideas and empirical evidence about the source monitoring processes underlying both true and false memories. Neuropsychological studies show that certain forms of brain damage (such as combined frontal and medial-temporal lesions) might result in profound source confusions, called confabulations. Neuroimaging techniques provide new evidence regarding more specific links between underlying brain mechanisms and the normal cognitive processes involved in evaluating memories. One hypothesis is that the right prefrontal cortex (PFC) subserves heuristic judgments based on easily assessed qualities (such as familiarity or perceptual detail) and the left PFC (or the right and left PFC together) subserves more systematic judgments requiring more careful analysis of memorial qualities or retrieval and evaluation of additional supporting or disconfirming information. Such heuristic and systematic processes can be disrupted not only by brain damage but also, for example, by hypnosis, social demands and motivational factors, suggesting caution in the methods used by `memory exploring' professions (therapists, police officers, lawyers, etc.) in order to avoid inducing false memories.

  19. Discovery, cloning and characterisation of proline specific prolyl endopeptidase, a gluten degrading thermo-stable enzyme from Sphaerobacter thermophiles

    DEFF Research Database (Denmark)

    Shetty, Radhakrishna; Vestergaard, Mike; Jessen, Flemming

    2017-01-01

    processes occur at elevated temperature. We present in this paper, the discovery, cloning and characterisation of a novel recombinant thermostable gluten degrading enzyme, a proline specific prolyl endoprotease (PEP) from Sphaerobacter thermophiles. The molecular mass of the prolyl endopeptidase......Gluten free products have emerged during the last decades, as a result of a growing public concern and technological advancements allowing gluten reduction in food products. One approach is to use gluten degrading enzymes, typically at low or ambient temperatures, whereas many food production...... was estimated to be 77 kDa by using SDS-PAGE. Enzyme activity assays with a synthetic dipeptide Z-Gly-Pro-p-nitroanilide as the substrate revealed that the enzyme had optimal activity at pH 6.6 and was most active from pH 5.0-8.0. The optimum temperature was 63 °C and residual activity after one hour incubation...

  20. Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons.

    Science.gov (United States)

    Song, M-K; Liu, H; Jiang, H-L; Yue, J-M; Hu, G-Y; Chen, H-Z

    2008-08-13

    Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (IK) with an IC50 value of 146.0+/-5.8 microM in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of IK and its recovery from inactivation, suggesting that talatisamine had no allosteric action on IK channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific IK channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking IK channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.

  1. Evaluating Discovery Services Architectures in the Context of the Internet of Things

    Science.gov (United States)

    Polytarchos, Elias; Eliakis, Stelios; Bochtis, Dimitris; Pramatari, Katerina

    As the "Internet of Things" is expected to grow rapidly in the following years, the need to develop and deploy efficient and scalable Discovery Services in this context is very important for its success. Thus, the ability to evaluate and compare the performance of different Discovery Services architectures is vital if we want to allege that a given design is better at meeting requirements of a specific application. The purpose of this chapter is to provide a paradigm for the evaluation of different Discovery Services for the Internet of Things in terms of efficiency, scalability and performance through the use of simulations. The methodology presented uses the application of Discovery Services to a supply chain with the Service Lookup Service Discovery Service using OMNeT++, an open source network simulation suite. Then, we delve into the simulation design and the details of our findings.

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

    Science.gov (United States)

    Tanaka, Daisuke

    2010-03-01

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

  3. Finding viable models in SUSY parameter spaces with signal specific discovery potential

    Science.gov (United States)

    Burgess, Thomas; Lindroos, Jan Øye; Lipniacka, Anna; Sandaker, Heidi

    2013-08-01

    Recent results from ATLAS giving a Higgs mass of 125.5 GeV, further constrain already highly constrained supersymmetric models such as pMSSM or CMSSM/mSUGRA. As a consequence, finding potentially discoverable and non-excluded regions of model parameter space is becoming increasingly difficult. Several groups have invested large effort in studying the consequences of Higgs mass bounds, upper limits on rare B-meson decays, and limits on relic dark matter density on constrained models, aiming at predicting superpartner masses, and establishing likelihood of SUSY models compared to that of the Standard Model vis-á-vis experimental data. In this paper a framework for efficient search for discoverable, non-excluded regions of different SUSY spaces giving specific experimental signature of interest is presented. The method employs an improved Markov Chain Monte Carlo (MCMC) scheme exploiting an iteratively updated likelihood function to guide search for viable models. Existing experimental and theoretical bounds as well as the LHC discovery potential are taken into account. This includes recent bounds on relic dark matter density, the Higgs sector and rare B-mesons decays. A clustering algorithm is applied to classify selected models according to expected phenomenology enabling automated choice of experimental benchmarks and regions to be used for optimizing searches. The aim is to provide experimentalist with a viable tool helping to target experimental signatures to search for, once a class of models of interest is established. As an example a search for viable CMSSM models with τ-lepton signatures observable with the 2012 LHC data set is presented. In the search 105209 unique models were probed. From these, ten reference benchmark points covering different ranges of phenomenological observables at the LHC were selected.

  4. Hippocampal size is related to short-term true and false memory, and right fusiform size is related to long-term true and false memory.

    Science.gov (United States)

    Zhu, Bi; Chen, Chuansheng; Loftus, Elizabeth F; He, Qinghua; Lei, Xuemei; Dong, Qi; Lin, Chongde

    2016-11-01

    There is a keen interest in identifying specific brain regions that are related to individual differences in true and false memories. Previous functional neuroimaging studies showed that activities in the hippocampus, right fusiform gyrus, and parahippocampal gyrus were associated with true and false memories, but no study thus far has examined whether the structures of these brain regions are associated with short-term and long-term true and false memories. To address that question, the current study analyzed data from 205 healthy young adults, who had valid data from both structural brain imaging and a misinformation task. In the misinformation task, subjects saw the crime scenarios, received misinformation, and took memory tests about the crimes an hour later and again after 1.5 years. Results showed that bilateral hippocampal volume was associated with short-term true and false memories, whereas right fusiform gyrus volume and surface area were associated with long-term true and false memories. This study provides the first evidence for the structural neural bases of individual differences in short-term and long-term true and false memories.

  5. Intact suppression of increased false recognition in schizophrenia.

    Science.gov (United States)

    Weiss, Anthony P; Dodson, Chad S; Goff, Donald C; Schacter, Daniel L; Heckers, Stephan

    2002-09-01

    Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia. The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words. Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding. Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population.

  6. Knowledge discovery with classification rules in a cardiovascular dataset.

    Science.gov (United States)

    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.

  7. Usability of Discovery Portals

    OpenAIRE

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

    2013-01-01

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

  8. Bayesian centroid estimation for motif discovery.

    Science.gov (United States)

    Carvalho, Luis

    2013-01-01

    Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  9. Bayesian centroid estimation for motif discovery.

    Directory of Open Access Journals (Sweden)

    Luis Carvalho

    Full Text Available Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  10. Creating a false memory in the hippocampus.

    Science.gov (United States)

    Ramirez, Steve; Liu, Xu; Lin, Pei-Ann; Suh, Junghyup; Pignatelli, Michele; Redondo, Roger L; Ryan, Tomás J; Tonegawa, Susumu

    2013-07-26

    Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram-bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.

  11. 7 CFR 1.641 - How may parties obtain discovery of information needed for the case?

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false How may parties obtain discovery of information needed for the case? 1.641 Section 1.641 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE... legal theories of an attorney. (g) Experts. Unless restricted by the ALJ, a party may discover any facts...

  12. Myocardial infarction false alarm: initial electrocardiogram and cardiac enzymes.

    Science.gov (United States)

    Gupta, Esha Das; Sakthiswary, Rajalingham

    2014-05-01

    The objectives of this study were to determine the incidence of a myocardial infarction "false alarm" and evaluate the efficacy of the initial electrocardiogram and cardiac enzymes in diagnosing myocardial infarction in Malaysia. We recruited patients who were admitted with suspected myocardial infarction from June to August 2008. The medical records of these patients were reviewed for the initial electrocardiogram, initial cardiac enzyme levels (creatinine kinase-MB and troponin T), and the final diagnosis upon discharge. The subjects were stratified into 2 groups: true myocardial infarction, and false alarm. 125 patients were enrolled in this study. Following admission and further evaluation, the diagnosis was revised from myocardial infarction to other medical conditions in 48 (38.4%) patients. The sensitivity and specificity of the initial ischemic electrocardiographic changes were 54.5% and 70.8%, respectively. Raised cardiac enzymes had a sensitivity of 44.3% and specificity of 95.8%. A significant proportion of patients in Malaysia are admitted with a false-alarm myocardial infarction. The efficacy of the electrocardiogram in diagnosing myocardial infarction in Malaysia was comparable to the findings of Western studies, but the cardiac enzymes had a much lower sensitivity.

  13. Analysis of false positive and false negative cytological diagnosis of breast lesions

    International Nuclear Information System (INIS)

    Jamal, Awtif A.; Mansoor, I.

    2001-01-01

    To study the reasons for interpretive errors in false negative and false positive diagnosis of breast carcinoma on fine needle aspiration cytology material. We reviewed only those cases in which cytohistological discrepancies were found, where the cytologic material was abnormal and to some extent misinterpreted or both. There was only one false negative case (false negative fraction 0.32%) proved histologically as ductal carcinoma and four false positive cases (false positive fraction 1.2%); 2 fibroadenoma; 1 fibrocystic disease; and 1 stromal fibrosis. Smears of the two false positive fibroadenoma cases showed very high cellularity, overcrowded clusters and frequent stripped nuclei. The fibrocystic case showed tight clusters of apocrine cells and sheets of loosely aggregated macrophages that were over interpreted. Smears of the false negative ductal carcinoma was hypocellular overall, and the cells showed minimal nuclear pleomorphism. Overcrowded clusters and hypercellular smears should be carefully assessed for uniformity of cells and detailed nuclear and cytomorphological features. If the full-blown malignant cytomorphological changes are not visible, a diagnosis of suspicious or inconclusive should be made and frozen section recommended before surgery. Hypocellularity and relatively nuclear monomorphism are the reasons for failure to diagnose malignant breast lesions. Careful attention should be paid to extreme nuclear monomorphism and absence of naked bipolar cells. A cytologically atypical or suspicious diagnosis together with positive radiological and clinical findings should suggest a diagnosis of malignancy. (author)

  14. Usability of Discovery Portals

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

  16. The importance of material-processing interactions in inducing false memories.

    Science.gov (United States)

    Chan, Jason C K; McDermott, Kathleen B; Watson, Jason M; Gallo, David A

    2005-04-01

    Deep encoding, relative to shallow encoding, has been shown to increase the probability of false memories in the Deese/Roediger-McDermott (DRM) paradigm (Thapar & McDermott, 2001; Toglia, Neuschatz, & Goodwin, 1999). In two experiments, we showed important limitations on the generalizability of this phenomenon; these limitations are clearly predicted by existing theories regarding the mechanisms underlying such false memories (e.g., Roediger, Watson, McDermott, & Gallo, 2001). Specifically, asking subjects to attend to phonological relations among lists of phonologically associated words (e.g., weep, steep, etc.) increased the likelihood of false recall (Experiment 1) and false recognition (Experiment 2) of a related, nonpresented associate (e.g., sleep), relative to a condition in which subjects attended to meaningful relations among the words. These findings occurred along with a replication of prior findings (i.e., a semantic encoding task, relative to a phonological encoding task, enhanced the likelihood of false memory arising from a list of semantically associated words), and they place important constraints on theoretical explanations of false memory.

  17. Exposure to suggestion and creation of false auditory memories.

    Science.gov (United States)

    Vernon, B; Nelson, E

    2000-02-01

    The experiment investigated the possibility of creating false auditory memory through exposure to suggestion. Research by Loftus and others has indicated that, through suggestion, false memories can be created. Participants viewed a short film and were given a 9-item questionnaire. Eight questions were used as filler while one question asked respondents to recall a phrase one character had said. Although the character actually said nothing, 23 of 30 respondents recalled having heard him speak and specifically recalled his words. This statistically significant result shows that auditory memories can also be created.

  18. 22 CFR 521.21 - Discovery.

    Science.gov (United States)

    2010-04-01

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

  19. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study.

    Directory of Open Access Journals (Sweden)

    Simina M Boca

    Full Text Available Serum metabolite profiling in Duchenne muscular dystrophy (DMD may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.

  2. Rationality in discovery : a study of logic, cognition, computation and neuropharmacology

    NARCIS (Netherlands)

    Bosch, Alexander Petrus Maria van den

    2001-01-01

    Part I Introduction The specific problem adressed in this thesis is: what is the rational use of theory and experiment in the process of scientific discovery, in theory and in the practice of drug research for Parkinson’s disease? The thesis aims to answer the following specific questions: what is:

  3. Diagnostic Invasiveness and Psychosocial Consequences of False-Positive Mammography

    DEFF Research Database (Denmark)

    Heleno, Bruno M.; Siersma, Volkert Dirk; Brodersen, John

    2015-01-01

    PURPOSE: We undertook a study to assess whether women with false-positivemammography have worse psychosocial consequences if managed with aworkup that involves a biopsy (invasive group) than if managed with only additional imaging (noninvasive group). METHODS: We performed subgroup analysis...... of a cohort study of 454 womenwith abnormal screening mammography and 908 matched control women withnormal results. Using a condition-specific questionnaire (Consequences of Screening in Breast Cancer), we assessed 12 psychosocial consequences at 5 time points (0, 1, 6, 18, and 36 months after final diagnosis......) and compared the 2 groups of women with false-positives (invasive and noninvasive management groups). RESULTS: Among the 252 women with false-positive mammography eligible forthis study, psychosocial consequences were similar for those managed invasivelyand those managed noninvasively during the 36 months...

  4. Preference vs. Authority: A Comparison of Student Searching in a Subject-Specific Indexing and Abstracting Database and a Customized Discovery Layer

    Science.gov (United States)

    Dahlen, Sarah P. C.; Hanson, Kathlene

    2017-01-01

    Discovery layers provide a simplified interface for searching library resources. Libraries with limited finances make decisions about retaining indexing and abstracting databases when similar information is available in discovery layers. These decisions should be informed by student success at finding quality information as well as satisfaction…

  5. Sea Level Rise Data Discovery

    Science.gov (United States)

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

    2016-12-01

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

  6. Veridical and false recall in adults who stutter.

    Science.gov (United States)

    Byrd, Courtney T; Sheng, Li; Ratner, Nan Bernstein; Gkalitsiou, Zoi

    2015-02-01

    This study used a false memory paradigm to explore the veridical and false recall of adults who stutter. Twelve adults who stutter and 12 age-matched typically fluent peers listened to and then verbally recalled lists of words that consisted of either semantic or phonological associates or an equal number of semantic and phonological associates (i.e., hybrid condition) of a single, unpresented critical "lure" word. Three parameters of recall performance were measured across these 3 conditions: (a) number of accurately recalled words, (b) order of recall (primacy vs. recency effect), and (c) number of critical lures produced (i.e., false memories). Significant group differences were noted in recall accuracy specific to list type and also list position as well as relative to critical lure productions. Results suggest that certain basic memory processes (i.e., recency effect) and the processing of gist semantic information are largely intact in adults who stutter, but recall of verbatim phonological information and subvocal rehearsal may be deficient.

  7. Induced Pluripotent Stem Cells for Regenerative Cardiovascular Therapies and Biomedical Discovery

    OpenAIRE

    Nsair, Ali; MacLellan, W. Robb

    2011-01-01

    The discovery of induced pluripotent stem cells (iPSC) has, in the short time since their discovery, revolutionized the field of stem cell biology. This technology allows the generation of a virtually unlimited supply of cells with pluripotent potential similar to that of embryonic stem cells (ESC). However, in contrast to ESC, iPSC are not subject to the same ethical concerns and can be easily generated from living individuals. For the first time, patient-specific iPSC can be generated and o...

  8. Using the iPlant collaborative discovery environment.

    Science.gov (United States)

    Oliver, Shannon L; Lenards, Andrew J; Barthelson, Roger A; Merchant, Nirav; McKay, Sheldon J

    2013-06-01

    The iPlant Collaborative is an academic consortium whose mission is to develop an informatics and social infrastructure to address the "grand challenges" in plant biology. Its cyberinfrastructure supports the computational needs of the research community and facilitates solving major challenges in plant science. The Discovery Environment provides a powerful and rich graphical interface to the iPlant Collaborative cyberinfrastructure by creating an accessible virtual workbench that enables all levels of expertise, ranging from students to traditional biology researchers and computational experts, to explore, analyze, and share their data. By providing access to iPlant's robust data-management system and high-performance computing resources, the Discovery Environment also creates a unified space in which researchers can access scalable tools. Researchers can use available Applications (Apps) to execute analyses on their data, as well as customize or integrate their own tools to better meet the specific needs of their research. These Apps can also be used in workflows that automate more complicated analyses. This module describes how to use the main features of the Discovery Environment, using bioinformatics workflows for high-throughput sequence data as examples. © 2013 by John Wiley & Sons, Inc.

  9. Detecting and avoiding likely false-positive findings - a practical guide.

    Science.gov (United States)

    Forstmeier, Wolfgang; Wagenmakers, Eric-Jan; Parker, Timothy H

    2017-11-01

    Recently there has been a growing concern that many published research findings do not hold up in attempts to replicate them. We argue that this problem may originate from a culture of 'you can publish if you found a significant effect'. This culture creates a systematic bias against the null hypothesis which renders meta-analyses questionable and may even lead to a situation where hypotheses become difficult to falsify. In order to pinpoint the sources of error and possible solutions, we review current scientific practices with regard to their effect on the probability of drawing a false-positive conclusion. We explain why the proportion of published false-positive findings is expected to increase with (i) decreasing sample size, (ii) increasing pursuit of novelty, (iii) various forms of multiple testing and researcher flexibility, and (iv) incorrect P-values, especially due to unaccounted pseudoreplication, i.e. the non-independence of data points (clustered data). We provide examples showing how statistical pitfalls and psychological traps lead to conclusions that are biased and unreliable, and we show how these mistakes can be avoided. Ultimately, we hope to contribute to a culture of 'you can publish if your study is rigorous'. To this end, we highlight promising strategies towards making science more objective. Specifically, we enthusiastically encourage scientists to preregister their studies (including a priori hypotheses and complete analysis plans), to blind observers to treatment groups during data collection and analysis, and unconditionally to report all results. Also, we advocate reallocating some efforts away from seeking novelty and discovery and towards replicating important research findings of one's own and of others for the benefit of the scientific community as a whole. We believe these efforts will be aided by a shift in evaluation criteria away from the current system which values metrics of 'impact' almost exclusively and towards a system

  10. Decades of Discovery

    Science.gov (United States)

    2011-06-01

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

  11. Common characteristics of open source software development and applicability for drug discovery: a systematic review.

    Science.gov (United States)

    Ardal, Christine; Alstadsæter, Annette; Røttingen, John-Arne

    2011-09-28

    Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery. A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project. Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined. We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.

  12. Discovery and the atom

    International Nuclear Information System (INIS)

    1989-01-01

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

  13. Promzea: a pipeline for discovery of co-regulatory motifs in maize and other plant species and its application to the anthocyanin and phlobaphene biosynthetic pathways and the Maize Development Atlas.

    Science.gov (United States)

    Liseron-Monfils, Christophe; Lewis, Tim; Ashlock, Daniel; McNicholas, Paul D; Fauteux, François; Strömvik, Martina; Raizada, Manish N

    2013-03-15

    The discovery of genetic networks and cis-acting DNA motifs underlying their regulation is a major objective of transcriptome studies. The recent release of the maize genome (Zea mays L.) has facilitated in silico searches for regulatory motifs. Several algorithms exist to predict cis-acting elements, but none have been adapted for maize. A benchmark data set was used to evaluate the accuracy of three motif discovery programs: BioProspector, Weeder and MEME. Analysis showed that each motif discovery tool had limited accuracy and appeared to retrieve a distinct set of motifs. Therefore, using the benchmark, statistical filters were optimized to reduce the false discovery ratio, and then remaining motifs from all programs were combined to improve motif prediction. These principles were integrated into a user-friendly pipeline for motif discovery in maize called Promzea, available at http://www.promzea.org and on the Discovery Environment of the iPlant Collaborative website. Promzea was subsequently expanded to include rice and Arabidopsis. Within Promzea, a user enters cDNA sequences or gene IDs; corresponding upstream sequences are retrieved from the maize genome. Predicted motifs are filtered, combined and ranked. Promzea searches the chosen plant genome for genes containing each candidate motif, providing the user with the gene list and corresponding gene annotations. Promzea was validated in silico using a benchmark data set: the Promzea pipeline showed a 22% increase in nucleotide sensitivity compared to the best standalone program tool, Weeder, with equivalent nucleotide specificity. Promzea was also validated by its ability to retrieve the experimentally defined binding sites of transcription factors that regulate the maize anthocyanin and phlobaphene biosynthetic pathways. Promzea predicted additional promoter motifs, and genome-wide motif searches by Promzea identified 127 non-anthocyanin/phlobaphene genes that each contained all five predicted promoter

  14. "Drug" Discovery with the Help of Organic Chemistry.

    Science.gov (United States)

    Itoh, Yukihiro; Suzuki, Takayoshi

    2017-01-01

    The first step in "drug" discovery is to find compounds binding to a potential drug target. In modern medicinal chemistry, the screening of a chemical library, structure-based drug design, and ligand-based drug design, or a combination of these methods, are generally used for identifying the desired compounds. However, they do not necessarily lead to success and there is no infallible method for drug discovery. Therefore, it is important to explore medicinal chemistry based on not only the conventional methods but also new ideas. So far, we have found various compounds as drug candidates. In these studies, some strategies based on organic chemistry have allowed us to find drug candidates, through 1) construction of a focused library using organic reactions and 2) rational design of enzyme inhibitors based on chemical reactions catalyzed by the target enzyme. Medicinal chemistry based on organic chemical reactions could be expected to supplement the conventional methods. In this review, we present drug discovery with the help of organic chemistry showing examples of our explorative studies on histone deacetylase inhibitors and lysine-specific demethylase 1 inhibitors.

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

    Science.gov (United States)

    Kocevar, Nina; Komel, Radovan

    2014-01-01

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

  16. Effects of post-encoding stress on performance in the DRM false memory paradigm

    OpenAIRE

    Pardilla-Delgado, Enmanuelle; Alger, Sara E.; Cunningham, Tony J.; Kinealy, Brian; Payne, Jessica D.

    2016-01-01

    Numerous studies have investigated how stress impacts veridical memory, but how stress influences false memory formation remains poorly understood. In order to target memory consolidation specifically, a psychosocial stress (TSST) or control manipulation was administered following encoding of 15 neutral, semantically related word lists (DRM false memory task) and memory was tested 24 h later. Stress decreased recognition of studied words, while increasing false recognition of semantically rel...

  17. Filing false vice reports: Distinguishing true from false allegations of rape

    NARCIS (Netherlands)

    de Zutter, A.; Horselenberg, R.; van Koppen, P.J.

    2017-01-01

    False allegations constitute a problem since they may cause harm. To study the difference between true and false allegations we used a quasi-experimental approach. In the control condition likely true allegations were retrieved from criminal files. The victims, all female, were between the ages of

  18. Simultaneous SNP identification and assessment of allele-specific bias from ChIP-seq data

    Directory of Open Access Journals (Sweden)

    Ni Yunyun

    2012-09-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs have been associated with many aspects of human development and disease, and many non-coding SNPs associated with disease risk are presumed to affect gene regulation. We have previously shown that SNPs within transcription factor binding sites can affect transcription factor binding in an allele-specific and heritable manner. However, such analysis has relied on prior whole-genome genotypes provided by large external projects such as HapMap and the 1000 Genomes Project. This requirement limits the study of allele-specific effects of SNPs in primary patient samples from diseases of interest, where complete genotypes are not readily available. Results In this study, we show that we are able to identify SNPs de novo and accurately from ChIP-seq data generated in the ENCODE Project. Our de novo identified SNPs from ChIP-seq data are highly concordant with published genotypes. Independent experimental verification of more than 100 sites estimates our false discovery rate at less than 5%. Analysis of transcription factor binding at de novo identified SNPs revealed widespread heritable allele-specific binding, confirming previous observations. SNPs identified from ChIP-seq datasets were significantly enriched for disease-associated variants, and we identified dozens of allele-specific binding events in non-coding regions that could distinguish between disease and normal haplotypes. Conclusions Our approach combines SNP discovery, genotyping and allele-specific analysis, but is selectively focused on functional regulatory elements occupied by transcription factors or epigenetic marks, and will therefore be valuable for identifying the functional regulatory consequences of non-coding SNPs in primary disease samples.

  19. False memories for aggressive acts.

    Science.gov (United States)

    Laney, Cara; Takarangi, Melanie K T

    2013-06-01

    Can people develop false memories for committing aggressive acts? How does this process compare to developing false memories for victimhood? In the current research we used a simple false feedback procedure to implant false memories for committing aggressive acts (causing a black eye or spreading malicious gossip) or for victimhood (receiving a black eye). We then compared these false memories to other subjects' true memories for equivalent events. False aggressive memories were all too easy to implant, particularly in the minds of individuals with a proclivity towards aggression. Once implanted, the false memories were indistinguishable from true memories for the same events, on several dimensions, including emotional content. Implications for aggression-related memory more generally as well as false confessions are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Foster, Anita K.; MacDonald, Jean B.

    2013-01-01

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

  1. Falsely elevated triiodothyronine values in radioimmunoassay

    International Nuclear Information System (INIS)

    Skovsted, L.; Moelholm Hansen, J.E.; Nygaard, B.

    1995-01-01

    Five patients with falsely elevated serum triiodothyronine (T 3 ) concentrations (>9 nmol/l) in a radioimmunoassay are reported. The high T 3 -values disagreed with the other thyroid variables investigated as well as with the clinical observations. In sera from all patients a normal non-specific binding of T 3 was found, thus excluding abnormal serum-protein-binding of the hormone. An ethanol extraction of T 3 from serum before RIA reduced the T 3 content in serum from all patients to normal levels (2.0-2.4 nmol/l). These findings indicate the presence in the sera of substances, probably of protein nature, that were interfering with the assay by binding the reagent-antibody and not the antigen. Addition of non-immune rabbit serum prevented this interference and normalized the T 3 -values (1.8-2.4 nmol/l). Thus the interfering substance in T 3 -RIA could be an anti-rabbit antibody, the interaction of which can be eliminated by a minor modification of the assay making it possible to differentiate true from false T 3 -values. (au) 16 refs

  2. Patterns of False Memory in Patients with Huntington's Disease.

    Science.gov (United States)

    Chen, I-Wen; Chen, Chiung-Mei; Wu, Yih-Ru; Hua, Mau-Sun

    2017-06-01

    Increased false memory recognition in patients with Huntington's disease (HD) has been widely reported; however, the underlying memory constructive processes remain unclear. The present study explored gist memory, item-specific memory, and monitoring ability in patients with HD. Twenty-five patients (including 13 patients with mild HD and 12 patients with moderate-to-severe HD) and 30 healthy comparison participants (HC) were recruited. We used the Deese-Roediger-McDermott (DRM) paradigm to investigate participants' false recognition patterns, along with neuropsychological tests to assess general cognitive function. Both mild and moderate-to-severe patients with HD showed significant executive functioning and episodic memory impairment. On the DRM tasks, both HD patient groups showed significantly impaired performance in tasks assessing unrelated false recognition and item-specific memory as compared to the HC group; moderate-to-severe patients performed more poorly than mild patients did. Only moderate-severe patients exhibited significantly poorer related false recognition index scores than HCs in the verbal DRM task; performance of HD patient groups was comparable to the HC group on the pictorial DRM task. It appears that diminished verbatim memory and monitoring ability are early signs of cognitive decline during the HD course. Conversely, gist memory is relatively robust, with only partial decline during advanced-stage HD. Our findings suggest that medial temporal lobe function is relatively preserved compared to that of frontal-related structures in early HD. Thus, gist-based memory rehabilitation programs might be beneficial for patients with HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

    Directory of Open Access Journals (Sweden)

    Ana Rita Lima

    2016-08-01

    Full Text Available Prostate cancer (PCa is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA levels and digital rectal examination. A decisive diagnosis of PCa is based on prostate biopsies; however, this approach can lead to false-positive and false-negative results. Therefore, it is important to discover new biomarkers for the diagnosis of PCa, preferably noninvasive ones. Metabolomics is an approach that allows the analysis of the entire metabolic profile of a biological system. As neoplastic cells have a unique metabolic phenotype related to cancer development and progression, the identification of dysfunctional metabolic pathways using metabolomics can be used to discover cancer biomarkers and therapeutic targets. In this study, we review several metabolomics studies performed in prostatic fluid, blood plasma/serum, urine, tissues and immortalized cultured cell lines with the objective of discovering alterations in the metabolic phenotype of PCa and thus discovering new biomarkers for the diagnosis of PCa. Encouraging results using metabolomics have been reported for PCa, with sarcosine being one of the most promising biomarkers identified to date. However, the use of sarcosine as a PCa biomarker in the clinic remains a controversial issue within the scientific community. Beyond sarcosine, other metabolites are considered to be biomarkers for PCa, but they still need clinical validation. Despite the lack of metabolomics biomarkers reaching clinical practice, metabolomics proved to be a powerful tool in the discovery of new biomarkers for PCa detection.

  4. Quantifying the Ease of Scientific Discovery.

    Science.gov (United States)

    Arbesman, Samuel

    2011-02-01

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

  5. 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.

  6. Negative affect promotes encoding of and memory for details at the expense of the gist: affect, encoding, and false memories.

    Science.gov (United States)

    Storbeck, Justin

    2013-01-01

    I investigated whether negative affective states enhance encoding of and memory for item-specific information reducing false memories. Positive, negative, and neutral moods were induced, and participants then completed a Deese-Roediger-McDermott (DRM) false-memory task. List items were presented in unique spatial locations or unique fonts to serve as measures for item-specific encoding. The negative mood conditions had more accurate memories for item-specific information, and they also had fewer false memories. The final experiment used a manipulation that drew attention to distinctive information, which aided learning for DRM words, but also promoted item-specific encoding. For the condition that promoted item-specific encoding, false memories were reduced for positive and neutral mood conditions to a rate similar to that of the negative mood condition. These experiments demonstrated that negative affective cues promote item-specific processing reducing false memories. People in positive and negative moods encode events differently creating different memories for the same event.

  7. The problem of false positives and false negatives in violent video game experiments.

    Science.gov (United States)

    Ferguson, Christopher J

    The problem of false positives and negatives has received considerable attention in behavioral research in recent years. The current paper uses video game violence research as an example of how such issues may develop in a field. Despite decades of research, evidence on whether violent video games (VVGs) contribute to aggression in players has remained mixed. Concerns have been raised in recent years that experiments regarding VVGs may suffer from both "false positives" and "false negatives." The current paper examines this issue in three sets of video game experiments, two sets of video game experiments on aggression and prosocial behaviors identified in meta-analysis, and a third group of recent null studies. Results indicated that studies of VVGs and aggression appear to be particularly prone to false positive results. Studies of VVGs and prosocial behavior, by contrast are heterogeneous and did not demonstrate any indication of false positive results. However, their heterogeneous nature made it difficult to base solid conclusions on them. By contrast, evidence for false negatives in null studies was limited, and little evidence emerged that null studies lacked power in comparison those highlighted in past meta-analyses as evidence for effects. These results are considered in light of issues related to false positives and negatives in behavioral science more broadly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery

    Science.gov (United States)

    Savino, Rocco; Paduano, Sergio; Preianò, Mariaimmacolata; Terracciano, Rosa

    2012-01-01

    In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets. PMID:23203042

  9. The future workforce in cancer prevention: advancing discovery, research, and technology.

    Science.gov (United States)

    Newhauser, Wayne D; Scheurer, Michael E; Faupel-Badger, Jessica M; Clague, Jessica; Weitzel, Jeffrey; Woods, Kendra V

    2012-05-01

    As part of a 2-day conference on October 15 and 16, 2009, a nine-member task force composed of scientists, clinicians, educators, administrators, and students from across the USA was formed to discuss research, discovery, and technology obstacles to progress in cancer prevention and control, specifically those related to the cancer prevention workforce. This article summarizes the task force's findings on the current state of the cancer prevention workforce in this area and its needs for the future. The task force identified two types of barriers impeding the current cancer prevention workforce in research, discovery, and technology from reaching its fullest potential: (1) limited cross-disciplinary research opportunities with underutilization of some disciplines is hampering discovery and research in cancer prevention, and (2) new research avenues are not being investigated because technology development and implementation are lagging. Examples of impediments and desired outcomes are provided in each of these areas. Recommended solutions to these problems are based on the goals of enhancing the current cancer prevention workforce and accelerating the pace of discovery and clinical translation.

  10. The discovery of the electric current

    Science.gov (United States)

    Cotti, Piero

    1995-02-01

    The first battery, the so called voltaic pile, turns out to be the only and hidden entrance to the world of electrodynamics. It was not until 20 years after Alessandro Volta's discovery that the realisation came that the sensational novelty of the voltaic pile was not the permanent voltage source but the current source. This was not to be expected, and had, therefore, not been searched for specifically, but, rather had been found through a great deal of luck and coincidence in experimentation.

  11. Discovery of convoys in trajectory databases

    DEFF Research Database (Denmark)

    Jeung, Hoyoung; Yiu, Man Lung; Zhou, Xiaofang

    2008-01-01

    a group of objects that have traveled together for some time. More specifically, this paper formalizes the concept of a convoy query using density-based notions, in order to capture groups of arbitrary extents and shapes. Convoy discovery is relevant for real-life applications in throughput planning...... convoys are further processed to obtain the actual convoys. Our comprehensive empirical study offers insight into the properties of the paper's proposals and demonstrates that the proposals are effective and efficient on real-world trajectory data....

  12. Social influence and mental routes to the production of authentic false memories and inauthentic false memories.

    Science.gov (United States)

    Wagner, Michael F; Skowronski, John J

    2017-05-01

    Two studies assessed the extent to which people incorporated false facts provided by bogus others into their own recognition memory reports, and how these false memory reports were affected by: (a) truth of the information in others' summaries supporting the false facts, (b) motivation to process stories and summaries, (c) source credibility, and (d) ease of remembering original facts. False memory report frequency increased when false facts in a summary were supported by true information and varied inversely with the ease with which original facts could be remembered. Results from a measure probing participants' memory perceptions suggest that some false memories are authentic: People sometimes lack awareness of both the incorporation of false facts into their memory reports and where the false facts came from. However, many false memories are inauthentic: Despite reporting a false memory, people sometimes retain knowledge of the original stimulus and/or the origin of false facts. Copyright © 2017. Published by Elsevier Inc.

  13. Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications

    International Nuclear Information System (INIS)

    Mordang, Jan-Jurre; Gubern-Mérida, Albert; Karssemeijer, Nico; Heeten, Gerard den

    2016-01-01

    Purpose: In the past decades, computer-aided detection (CADe) systems have been developed to aid screening radiologists in the detection of malignant microcalcifications. These systems are useful to avoid perceptual oversights and can increase the radiologists’ detection rate. However, due to the high number of false positives marked by these CADe systems, they are not yet suitable as an independent reader. Breast arterial calcifications (BACs) are one of the most frequent false positives marked by CADe systems. In this study, a method is proposed for the elimination of BACs as positive findings. Removal of these false positives will increase the performance of the CADe system in finding malignant microcalcifications. Methods: A multistage method is proposed for the removal of BAC findings. The first stage consists of a microcalcification candidate selection, segmentation and grouping of the microcalcifications, and classification to remove obvious false positives. In the second stage, a case-based selection is applied where cases are selected which contain BACs. In the final stage, BACs are removed from the selected cases. The BACs removal stage consists of a GentleBoost classifier trained on microcalcification features describing their shape, topology, and texture. Additionally, novel features are introduced to discriminate BACs from other positive findings. Results: The CADe system was evaluated with and without BACs removal. Here, both systems were applied on a validation set containing 1088 cases of which 95 cases contained malignant microcalcifications. After bootstrapping, free-response receiver operating characteristics and receiver operating characteristics analyses were carried out. Performance between the two systems was compared at 0.98 and 0.95 specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52% and the sensitivity increased from 62% up to 76% at a specificity of 0.95. Partial areas under the curve in the specificity

  14. Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications

    Energy Technology Data Exchange (ETDEWEB)

    Mordang, Jan-Jurre, E-mail: Jan-Jurre.Mordang@radboudumc.nl; Gubern-Mérida, Albert; Karssemeijer, Nico [Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen 6525 GA (Netherlands); Heeten, Gerard den [The National Training Centre for Breast Cancer Screening, Nijmegen 6503 GJ, The Netherlands and Department of Radiology, Amsterdam Medical Center, Amsterdam 1100 DD (Netherlands)

    2016-04-15

    Purpose: In the past decades, computer-aided detection (CADe) systems have been developed to aid screening radiologists in the detection of malignant microcalcifications. These systems are useful to avoid perceptual oversights and can increase the radiologists’ detection rate. However, due to the high number of false positives marked by these CADe systems, they are not yet suitable as an independent reader. Breast arterial calcifications (BACs) are one of the most frequent false positives marked by CADe systems. In this study, a method is proposed for the elimination of BACs as positive findings. Removal of these false positives will increase the performance of the CADe system in finding malignant microcalcifications. Methods: A multistage method is proposed for the removal of BAC findings. The first stage consists of a microcalcification candidate selection, segmentation and grouping of the microcalcifications, and classification to remove obvious false positives. In the second stage, a case-based selection is applied where cases are selected which contain BACs. In the final stage, BACs are removed from the selected cases. The BACs removal stage consists of a GentleBoost classifier trained on microcalcification features describing their shape, topology, and texture. Additionally, novel features are introduced to discriminate BACs from other positive findings. Results: The CADe system was evaluated with and without BACs removal. Here, both systems were applied on a validation set containing 1088 cases of which 95 cases contained malignant microcalcifications. After bootstrapping, free-response receiver operating characteristics and receiver operating characteristics analyses were carried out. Performance between the two systems was compared at 0.98 and 0.95 specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52% and the sensitivity increased from 62% up to 76% at a specificity of 0.95. Partial areas under the curve in the specificity

  15. Stem cell technology for drug discovery and development.

    Science.gov (United States)

    Hook, Lilian A

    2012-04-01

    Stem cells have enormous potential to revolutionise the drug discovery process at all stages, from target identification through to toxicology studies. Their ability to generate physiologically relevant cells in limitless supply makes them an attractive alternative to currently used recombinant cell lines or primary cells. However, realisation of the full potential of stem cells is currently hampered by the difficulty in routinely directing stem cell differentiation to reproducibly and cost effectively generate pure populations of specific cell types. In this article we discuss how stem cells have already been used in the drug discovery process and how novel technologies, particularly in relation to stem cell differentiation, can be applied to attain widespread adoption of stem cell technology by the pharmaceutical industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Adaptive false memory: Imagining future scenarios increases false memories in the DRM paradigm.

    Science.gov (United States)

    Dewhurst, Stephen A; Anderson, Rachel J; Grace, Lydia; van Esch, Lotte

    2016-10-01

    Previous research has shown that rating words for their relevance to a future scenario enhances memory for those words. The current study investigated the effect of future thinking on false memory using the Deese/Roediger-McDermott (DRM) procedure. In Experiment 1, participants rated words from 6 DRM lists for relevance to a past or future event (with or without planning) or in terms of pleasantness. In a surprise recall test, levels of correct recall did not vary between the rating tasks, but the future rating conditions led to significantly higher levels of false recall than the past and pleasantness conditions did. Experiment 2 found that future rating led to higher levels of false recognition than did past and pleasantness ratings but did not affect correct recognition. The effect in false recognition was, however, eliminated when DRM items were presented in random order. Participants in Experiment 3 were presented with both DRM lists and lists of unrelated words. Future rating increased levels of false recognition for DRM lures but did not affect correct recognition for DRM or unrelated lists. The findings are discussed in terms of the view that false memories can be associated with adaptive memory functions.

  17. The effect of articulatory suppression on implicit and explicit false memory in the DRM paradigm.

    Science.gov (United States)

    Van Damme, Ilse; Menten, Jan; d'Ydewalle, Gery

    2010-11-01

    Several studies have shown that reliable implicit false memory can be obtained in the DRM paradigm. There has been considerable debate, however, about whether or not conscious activation of critical lures during study is a necessary condition for this. Recent findings have revealed that articulatory suppression prevents subsequent false priming in an anagram task (Lovden & Johansson, 2003). The present experiment sought to replicate and extend these findings to an implicit word stem completion task, and to additionally investigate the effect of articulatory suppression on explicit false memory. Results showed an inhibitory effect of articulatory suppression on veridical memory, as well as on implicit false memory, whereas the level of explicit false memory was heightened. This suggests that articulatory suppression did not merely eliminate conscious lure activation, but had a more general capacity-delimiting effect. The drop in veridical memory can be attributed to diminished encoding of item-specific information. Superficial encoding also limited the spreading of semantic activation during study, which inhibited later false priming. In addition, the lack of item-specific and phenomenological details caused impaired source monitoring at test, resulting in heightened explicit false memory.

  18. 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.

  19. Discovery Driven Growth

    DEFF Research Database (Denmark)

    Bukh, Per Nikolaj

    2009-01-01

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

  20. 29 CFR 22.21 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  1. 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.

  2. The influence of perceptual similarity and individual differences on false memories in aging.

    Science.gov (United States)

    Dennis, Nancy A; Turney, Indira C

    2018-02-01

    Previous false memory research has suggested that older adults' false memories are based on an overreliance on gist processing in the absence of item-specific details. Yet, false memory studies have rarely taken into consideration the precise role of item-item similarity on the cognitive and neural mechanisms underlying perceptual false memories in older adults. In addition, work in our laboratory has suggested that when investigating the neural basis of false memories in older adults, it is equally as critical to take into account interindividual variability in behavior. With both factors in mind, the present study was the first to examine how both controlled, systematic differences in perceptual relatedness between targets and lures and individual differences in true and false recognition contribute to the neural basis of both true and false memories in older adults. Results suggest that between-subject variability in memory performance modulates neural activity in key regions associated with false memories in aging, whereas systematic differences in perceptual similarity did not modulate neural activity associated with false memories. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Magnetic resonance imaging of lumbar spine disc diseases. Frequency of false negatives

    International Nuclear Information System (INIS)

    Berthelot, J.M.; Maugars, Y.; Delecrin, Y.; Caillon, F.; Prost, A.

    1995-01-01

    Magnetic resonance imaging (MRI) has had an impressive impact on evaluation of degenerative diseases of the spine. Nevertheless, false negatives can occur on images involving lumbar discs. Degenerative disc diseases documented on discography and/or pathology examination of the discs can go unrecognized. Likewise sensitivity for the detection of protruding disc hernias is not totally satisfactory (20% false negatives). Finally, a magnetic resonance image visualizing displacement of the disc is not specific (10 to 15% false positives); images showing protrusion or hernia can be seen in 30% of asymptomatic patients. Although MRI gives slightly more information than other imaging techniques, false images do exist. Moreover, the usefulness of MRI to demonstrate disc disease in case of a negative CT-scan remains to be demonstrated. (authors). 26 refs

  4. Memory for media: investigation of false memories for negatively and positively charged public events.

    Science.gov (United States)

    Porter, Stephen; Taylor, Kristian; Ten Brinke, Leanne

    2008-01-01

    Despite a large body of false memory research, little has addressed the potential influence of an event's emotional content on susceptibility to false recollections. The Paradoxical Negative Emotion (PNE) hypothesis predicts that negative emotion generally facilitates memory but also heightens susceptibility to false memories. Participants were asked whether they could recall 20 "widely publicised" public events (half fictitious) ranging in emotional valence, with or without visual cues. Participants recalled a greater number of true negative events (M=3.31/5) than true positive (M=2.61/5) events. Nearly everyone (95%) came to recall at least one false event (M=2.15 false events recalled). Further, more than twice as many participants recalled any false negative (90%) compared to false positive (41.7%) events. Negative events, in general, were associated with more detailed memories and false negative event memories were more detailed than false positive event memories. Higher dissociation scores were associated with false recollections of negative events, specifically.

  5. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  6. Discovery Mondays - The detectors: tracking particles

    CERN Multimedia

    2005-01-01

    View of a module from the LHCb vertex detector, which will be presented at the next Discovery Monday. How do you observe the invisible? In order to deepen still further our knowledge of the infinitely small, physicists accelerate beams of particles at close to the speed of light, then generate collisions between them at extraordinary energies, giving birth to showers of new particles. What are these particles? In order to find out, physicists transform themselves into detectives with the help of the detectors. Located around the collision area, these exceptional machines are made up of various layers, each of which detects and measures specific properties of the particles that travel through them. Powerful computers then reconstruct their trajectory and record their charge, mass and energy in order to build up a kind of particle ID card. At the next Discovery Monday you will be able to find out about the different methods used at CERN to detect particles. A cloud chamber will provide live images of the trac...

  7. Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications.

    Science.gov (United States)

    Mordang, Jan-Jurre; Gubern-Mérida, Albert; den Heeten, Gerard; Karssemeijer, Nico

    2016-04-01

    In the past decades, computer-aided detection (CADe) systems have been developed to aid screening radiologists in the detection of malignant microcalcifications. These systems are useful to avoid perceptual oversights and can increase the radiologists' detection rate. However, due to the high number of false positives marked by these CADe systems, they are not yet suitable as an independent reader. Breast arterial calcifications (BACs) are one of the most frequent false positives marked by CADe systems. In this study, a method is proposed for the elimination of BACs as positive findings. Removal of these false positives will increase the performance of the CADe system in finding malignant microcalcifications. A multistage method is proposed for the removal of BAC findings. The first stage consists of a microcalcification candidate selection, segmentation and grouping of the microcalcifications, and classification to remove obvious false positives. In the second stage, a case-based selection is applied where cases are selected which contain BACs. In the final stage, BACs are removed from the selected cases. The BACs removal stage consists of a GentleBoost classifier trained on microcalcification features describing their shape, topology, and texture. Additionally, novel features are introduced to discriminate BACs from other positive findings. The CADe system was evaluated with and without BACs removal. Here, both systems were applied on a validation set containing 1088 cases of which 95 cases contained malignant microcalcifications. After bootstrapping, free-response receiver operating characteristics and receiver operating characteristics analyses were carried out. Performance between the two systems was compared at 0.98 and 0.95 specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52% and the sensitivity increased from 62% up to 76% at a specificity of 0.95. Partial areas under the curve in the specificity range of 0.8-1.0 were

  8. The circumstances of minor planet discovery

    International Nuclear Information System (INIS)

    Pilcher, F.

    1989-01-01

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

  9. Transient medial prefrontal perturbation reduces false memory formation.

    Science.gov (United States)

    Berkers, Ruud M W J; van der Linden, Marieke; de Almeida, Rafael F; Müller, Nils C J; Bovy, Leonore; Dresler, Martin; Morris, Richard G M; Fernández, Guillén

    2017-03-01

    Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott (DRM) paradigm, where the studying of words that fit a common semantic schema are found to induce false memories for words that are congruent with the given schema, but were not studied. The medial prefrontal cortex (mPFC) has been ascribed the function of leveraging prior knowledge to influence encoding and retrieval, based on imaging and patient studies. Here, we used transcranial magnetic stimulation (TMS) to transiently perturb ongoing mPFC processing immediately before participants performed the DRM-task. We observed the predicted reduction in false recall of critical lures after mPFC perturbation, compared to two control groups, whereas veridical recall and recognition memory performance remained similar across groups. These data provide initial causal evidence for a role of the mPFC in biasing the assimilation of new memories and their consolidation as a function of prior knowledge. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Toxins and drug discovery.

    Science.gov (United States)

    Harvey, Alan L

    2014-12-15

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

  11. mHealth Visual Discovery Dashboard.

    Science.gov (United States)

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

    2017-09-01

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

  12. Service discovery at home

    NARCIS (Netherlands)

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

    2003-01-01

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

  13. 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.

  14. The cortical basis of true memory and false memory for motion.

    Science.gov (United States)

    Karanian, Jessica M; Slotnick, Scott D

    2014-02-01

    Behavioral evidence indicates that false memory, like true memory, can be rich in sensory detail. By contrast, there is fMRI evidence that true memory for visual information produces greater activity in earlier visual regions than false memory, which suggests true memory is associated with greater sensory detail. However, false memory in previous fMRI paradigms may have lacked sufficient sensory detail to recruit earlier visual processing regions. To investigate this possibility in the present fMRI study, we employed a paradigm that produced feature-specific false memory with a high degree of visual detail. During the encoding phase, moving or stationary abstract shapes were presented to the left or right of fixation. During the retrieval phase, shapes from encoding were presented at fixation and participants classified each item as previously "moving" or "stationary" within each visual field. Consistent with previous fMRI findings, true memory but not false memory for motion activated motion processing region MT+, while both true memory and false memory activated later cortical processing regions. In addition, false memory but not true memory for motion activated language processing regions. The present findings indicate that true memory activates earlier visual regions to a greater degree than false memory, even under conditions of detailed retrieval. Thus, the dissociation between previous behavioral findings and fMRI findings do not appear to be task dependent. Future work will be needed to assess whether the same pattern of true memory and false memory activity is observed for different sensory modalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Inception of a false memory by optogenetic manipulation of a hippocampal memory engram.

    Science.gov (United States)

    Liu, Xu; Ramirez, Steve; Tonegawa, Susumu

    2014-01-05

    Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory.

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

    Science.gov (United States)

    Wójcikowski, Maciej; Zielenkiewicz, Piotr; Siedlecki, Pawel

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-11-06

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

  18. 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.

  19. 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...

  20. Service Discovery At Home

    NARCIS (Netherlands)

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

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

  1. Sadder and less accurate? False memory for negative material in depression.

    Science.gov (United States)

    Joormann, Jutta; Teachman, Bethany A; Gotlib, Ian H

    2009-05-01

    Previous research has demonstrated that induced sad mood is associated with increased accuracy of recall in certain memory tasks; the effects of clinical depression, however, are likely to be quite different. The authors used the Deese-Roediger-McDermott paradigm to examine the impact of clinical depression on erroneous recall of neutral and/or emotional stimuli. Specifically, they presented Deese-Roediger-McDermott lists that were highly associated with negative, neutral, or positive lures and compared participants diagnosed with major depressive disorder and nondepressed control participants on the accuracy of their recall of presented material and their false recall of never-presented lures. Compared with control participants, major depressive disorder participants recalled fewer words that had been previously presented but were more likely to falsely recall negative lures; there were no differences between major depressive disorder and control participants in false recall of positive or neutral lures. These findings indicate that depression is associated with false memories of negative material.

  2. Synthetic biology of antimicrobial discovery.

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

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

  3. A fractionally cointegrated VAR analysis of price discovery in commodity futures markets

    DEFF Research Database (Denmark)

    Dolatabadi, Sepideh; Nielsen, Morten Ørregaard; Xu, Ke

    straightforward examination of the adjustment coefficients. In our empirical analysis we use the data from Figuerola-Ferretti and Gonzalo (2010), who conduct a similar analysis using the usual (non-fractional) CVAR model. Our first finding is that, for all markets except copper, the fractional integration......In this paper we apply the recently developed fractionally cointegrated vector autoregressive (FCVAR) model to analyze price discovery in the spot and futures markets for five non-ferrous metals (aluminium, copper, lead, nickel, and zinc). The FCVAR model allows for long memory (fractional...... to the results from the non-fractional model, we find slightly more evidence of price discovery in the spot market. Specifically, using standard likelihood ratio tests, we do not reject the hypothesis that price discovery takes place exclusively in the spot (futures) market for copper, lead, and zinc (aluminium...

  4. Genome-scale metabolic models as platforms for strain design and biological discovery.

    Science.gov (United States)

    Mienda, Bashir Sajo

    2017-07-01

    Genome-scale metabolic models (GEMs) have been developed and used in guiding systems' metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models.

  5. Is it SUSY? -first steps after an LHC discovery

    CERN Multimedia

    CERN. Geneva

    2008-01-01

    A missing energy discovery is possible at the LHC in the first year of running. The origin of such a signal could be any of a huge number of models of supersymmetry, or non-supersymmetric models with extra dimensions or "little Higgs". Recently we have developed a realistic strategy to rapidly narrow the list of candidate theories at, or close to, the moment of discovery. The strategy is based on robust ratios of inclusive counts of simple physics objects. We studied specific cases showing discrimination of look- alike models in simulated data sets that are at least 10 to 100 times smaller than used in previous studies. We discriminate supersymmetry models from non-supersymmetric look-alikes with only 100 pb-1 of simulated data, using combinations of observables that trace back to differences in spin.

  6. Bioinformatics Tools for the Discovery of New Nonribosomal Peptides

    DEFF Research Database (Denmark)

    Leclère, Valérie; Weber, Tilmann; Jacques, Philippe

    2016-01-01

    -dimensional structure of the peptides can be compared with the structural patterns of all known NRPs. The presented workflow leads to an efficient and rapid screening of genomic data generated by high throughput technologies. The exploration of such sequenced genomes may lead to the discovery of new drugs (i......This chapter helps in the use of bioinformatics tools relevant to the discovery of new nonribosomal peptides (NRPs) produced by microorganisms. The strategy described can be applied to draft or fully assembled genome sequences. It relies on the identification of the synthetase genes...... and the deciphering of the domain architecture of the nonribosomal peptide synthetases (NRPSs). In the next step, candidate peptides synthesized by these NRPSs are predicted in silico, considering the specificity of incorporated monomers together with their isomery. To assess their novelty, the two...

  7. Discovery Mondays: 'Separating science from fiction'

    CERN Multimedia

    2006-01-01

    Photo credit: ESA/NASA, the AVO project and Paolo PadovaniDoes the imaginary word of fiction always end up becoming scientific reality? What futuristic visions can we extrapolate from today's technologies? Here is a short quiz to test your knowledge. Can YOU tell truth from fiction? True False The laser swords featuring in the Star Wars films really exist. Time travel is possible using black holes. You could eat a cake of antimatter. Levitation vehicles really exist. Dan Brown is a space alien. How can you distinguish truth from fiction, dreams from reality, real science and technology from the sci-fi fantasies so realistically described in novels, television and cinema? You are invited to come and discuss these questions at a Discovery Monday at the very frontiers of science..... Join us at Microcosm (Reception, Building 33, Meyrin site), on Monday, 4 September from 7:30 p.m. to 9 p.m. Entrance Free The event will be conducted in French. http://www.cern.ch/LundisDecouverte/ ...

  8. Reporting instructions significantly impact false positive rates when reading chest radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J. [The University of Sydney, Medical Image Optimisation and Perception Group, Discipline of Medical Radiation Sciences, Faculty of Health Sciences, Lidcombe, NSW (Australia)

    2016-10-15

    To determine the impact of specific reporting tasks on the performance of radiologists when reading chest radiographs. Ten experienced radiologists read a set of 40 postero-anterior (PA) chest radiographs: 21 nodule free and 19 with a proven solitary nodule. There were two reporting conditions: an unframed task (UFT) to report any abnormality and a framed task (FT) reporting only lung nodule/s. Jackknife free-response operating characteristic (JAFROC) figure of merit (FOM), specificity, location sensitivity and number of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) decisions were used for analysis. JAFROC FOM for tasks showed a significant reduction in performance for framed tasks (P = 0.006) and an associated decrease in specificity (P = 0.011) but no alteration to the location sensitivity score. There was a significant increase in number of FP decisions made during framed versus unframed tasks for nodule-containing (P = 0.005) and nodule-free (P = 0.011) chest radiographs. No significant differences in TP were recorded. Radiologists report more FP decisions when given specific reporting instructions to search for nodules on chest radiographs. The relevance of clinical history supplied to radiologists is called into question and may induce a negative effect. (orig.)

  9. Reporting instructions significantly impact false positive rates when reading chest radiographs

    International Nuclear Information System (INIS)

    Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J.

    2016-01-01

    To determine the impact of specific reporting tasks on the performance of radiologists when reading chest radiographs. Ten experienced radiologists read a set of 40 postero-anterior (PA) chest radiographs: 21 nodule free and 19 with a proven solitary nodule. There were two reporting conditions: an unframed task (UFT) to report any abnormality and a framed task (FT) reporting only lung nodule/s. Jackknife free-response operating characteristic (JAFROC) figure of merit (FOM), specificity, location sensitivity and number of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) decisions were used for analysis. JAFROC FOM for tasks showed a significant reduction in performance for framed tasks (P = 0.006) and an associated decrease in specificity (P = 0.011) but no alteration to the location sensitivity score. There was a significant increase in number of FP decisions made during framed versus unframed tasks for nodule-containing (P = 0.005) and nodule-free (P = 0.011) chest radiographs. No significant differences in TP were recorded. Radiologists report more FP decisions when given specific reporting instructions to search for nodules on chest radiographs. The relevance of clinical history supplied to radiologists is called into question and may induce a negative effect. (orig.)

  10. Radio Resource Management for V2V Discovery

    DEFF Research Database (Denmark)

    Alvarez, Beatriz Soret; Gatnau, Marta; Kovács, Istvan

    2016-01-01

    Big expectations are put into vehicular communications (V2X) for a safer and more intelligent driving. With human lives at risk, the system cannot afford to fail, which translates into very stringent reliability and latency requirements to the radio network. One of the challenges is to find...... efficient radio resource management (RRM) strategies for direct vehicle-to-vehicle (V2V) communication that can fulfil the requirements even with high traffic density. In cellular networks, a device-to-device (D2D) communication is usually split into two phases: the discovery process, for node awareness...... of each other; and the communication phase itself, where data exchange takes place. In the case of V2V, the discovery phase can utilize the status information that cars broadcast periodically as the beacons to detect the presence of neighbouring cars. For the delivery of specific messages (e...

  11. 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

  12. The π discovery

    International Nuclear Information System (INIS)

    Fowler, P.H.

    1988-01-01

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

  13. The false positive exercise test

    International Nuclear Information System (INIS)

    Moritani, Kohshiro; Matsuda, Yasuo; Ozaki, Masaharu; Ogawa, Hiroshi; Ichiyama, Masaji; Matsuda, Masako; Kusukawa, Reizo

    1986-01-01

    Exercise tests with sublingual nitroglycerin were performed on 7 patients with true positive and 8 patients with false positive exercise test results. Four of 7 patients with true positive changes and 8 patients with false positive changes underwent exercise cardiac scintigraphy. Scintigrams showed perfusion defects in 4 patients with true positive outcomes, and no perfusion defect in 8 patients with false positive outcomes. Exercise tests with sublingual nitroglycerin were performed with the same load as that without nitroglycerin. In all 7 patients with true positive exercise test results, ST segment depression observed in the control exercise test was not observed in the nitroglycerin exercise test. In the false positive patients, ST segment depression observed in the control exercise test remained unchanged in 7 of 8 patients receiving nitroglycerin. Exercise tests with sublingual nitroglycerin as well as exercise cardiac scintigraphy are valuable tods in differentiating false positive from true positive patients. Furthermore, these data suggest that ST segment depression in the false positive patients may not be related to myocardial ischemia. (author)

  14. Synthetic biology of antimicrobial discovery

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

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

  15. '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”.

  16. Computational methods in drug discovery

    OpenAIRE

    Sumudu P. Leelananda; Steffen Lindert

    2016-01-01

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

  17. Haloperidol increases false recognition memory of thematically related pictures in healthy volunteers.

    Science.gov (United States)

    Guarnieri, Regina V; Buratto, Luciano G; Gomes, Carlos F A; Ribeiro, Rafaela L; de Souza, Altay A Lino; Stein, Lilian M; Galduróz, José C; Bueno, Orlando F A

    2017-01-01

    Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D 2 -receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Interrogated with Intellectual Disabilities: The Risks of False Confession.

    Science.gov (United States)

    Schatz, Samson J

    2018-02-01

    False confessions happen. At least 245 people have been exonerated from convictions in cases featuring confessions that were simply not true. Confessions offer a narrative that allows law enforcement, and society in general, to neatly resolve cases with apparent clarity and closure. And yet the pressures officers place on suspects to provide that closure weigh disproportionately on the vulnerable, including individuals with intellectual disabilities. These individuals are disadvantaged at every step of the custodial interrogation, and they face heightened risks of falsely confessing. Moreover, the principal judicial safeguards against false confessions--assessing a suspect's Miranda waiver and determining whether a confession was voluntarily given within the bounds of the Fourteenth Amendment’s Due Process Clause--provide little protection for the innocent with intellectual disabilities. Few pieces of scholarship focus specifically on the heightened risks faced by individuals with intellectual disabilities throughout the process of police interrogation. This Note describes the various ways these individuals are disadvantaged. And it offers an additional data point illustrating the vulnerability of people with intellectual disabilities. This Note analyzes the 245 individuals (as of June 2, 2017) on the National Registry of Exonerations who have falsely confessed. Over one-quarter of them display indicia of intellectual disability. This percentage dwarfs the prevalence of people with intellectual disabilities in the general population and even exceeds most estimates of the proportion of the prison population suffering from intellectual disabilities. This Note concludes with several policy and doctrinal suggestions to better protect individuals with intellectual disabilities from the risks of false confession.

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

    Science.gov (United States)

    Moore, Kate B.; Greene, Courtney

    2012-01-01

    Within the next few years, traditional online public access catalogs will be replaced by more robust and interconnected discovery layers that can serve as primary public interfaces to simultaneously search many separate collections of resources. Librarians have envisioned this type of discovery tool since the 1980s, and research shows that…

  20. 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.

  1. 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.

  2. 29 CFR 18.13 - Discovery methods.

    Science.gov (United States)

    2010-07-01

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

  3. 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

  4. How Formal Methods Impels Discovery: A Short History of an Air Traffic Management Project

    Science.gov (United States)

    Butler, Ricky W.; Hagen, George; Maddalon, Jeffrey M.; Munoz, Cesar A.; Narkawicz, Anthony; Dowek, Gilles

    2010-01-01

    In this paper we describe a process of algorithmic discovery that was driven by our goal of achieving complete, mechanically verified algorithms that compute conflict prevention bands for use in en route air traffic management. The algorithms were originally defined in the PVS specification language and subsequently have been implemented in Java and C++. We do not present the proofs in this paper: instead, we describe the process of discovery and the key ideas that enabled the final formal proof of correctness

  5. False memory production :effects of self-consistent false information and motivated cognition

    OpenAIRE

    Brown, Martha

    1996-01-01

    Remembrance of one's personal past and the development of false memories have recently received intense public scrutiny. Based upon self-schema (Markus, 1977) and selfverification (Swann, 1987) theories, two studies were conducted to investigate the hypothesis that a self-schema guides cognitive processing of self-relevant information and thereby influences the construction of a memory that includes false information, particularly more so if this information is self-schema consistent than ...

  6. 41 CFR 60-30.33 - Discovery.

    Science.gov (United States)

    2010-07-01

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

  7. 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...

  8. False-negative type-specific glycoprotein G antibody responses in STI clinic patients with recurrent HSV-1 or HSV-2 DNA positive genital herpes, The Netherlands.

    Science.gov (United States)

    van Rooijen, Martijn S; Roest, Wim; Hansen, Gino; Kwa, David; de Vries, Henry J C

    2016-06-01

    Herpes simplex virus (HSV) type-discriminating antibody tests (glycoprotein G (gG) directed) are used to identify naïve persons and differentiate acute infections from recurrences. We studied test characteristics of three commercially available antibody tests in patients with recurrent (established by viral PCR tests) herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) genital herpes episodes. Serum samples (at minimum 3 months after t=0) were examined for the presence of gG-1-specific or gG-2-specific antibodies using the HerpeSelect 1 and 2 Immunoblot IgG, the HerpeSelect 1 and 2 enzyme linked immunoassays IgG and the LIAISON HSV-1 and HSV-2 IgG indirect chemiluminescence immunoassays. The immunoblot was HSV-1 positive in 70.6% (95% CI 44.0% to 89.7%), the LIAISON in 88.2% (95% CI 63.5% to 98.5%) and the ELISA in 82.4% (95% CI 56.6% to 96.2%) of the 17 patients with a recurrent HSV-1 episode. From 33 patients with a recurrent HSV-2 episode, the immunoblot was HSV-2 positive in 84.8% (95% CI 68.1% to 94.9%), the LIAISON in 69.7% (95% CI 51.3% to 84.4%) and the ELISA in 84.8% (95% CI 68.1% to 94.9%). Among 15/17 (88.2%; 95% CI 63.5% to 98.5%) patients with HSV-1 and 30/33 (90.1%; 95% CI 75.7% to 98.1%) patients with HSV-2, HSV-1 or HSV-2 antibodies, respectively, were detected in at least one of the three antibody tests. Commercial type-specific gG HSV-1 or HSV-2 antibody assays were false negative in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions. The clinical and epidemiological use of type-specific HSV serology can be hampered by false-negative results, especially if based on a single test. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Personal discovery in diabetes self-management: Discovering cause and effect using self-monitoring data.

    Science.gov (United States)

    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

  10. 19 CFR 111.32 - False information.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false False information. 111.32 Section 111.32 Customs... CUSTOMS BROKERS Duties and Responsibilities of Customs Brokers § 111.32 False information. A broker must... procure the giving of, any false or misleading information or testimony in any matter pending before the...

  11. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Science.gov (United States)

    Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

    2015-01-01

    Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  12. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Directory of Open Access Journals (Sweden)

    Leslie Shanks

    Full Text Available Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367 in the VL group compared to 7.9% (200/2526 in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively.The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  13. Scout or Cavalry? Optimal Discovery Strategies for GRBs

    International Nuclear Information System (INIS)

    Nemiroff, Robert J.

    2004-01-01

    Many present and past gamma-ray burst (GRB) detectors try to be not only a 'scout', discovering new GRBs, but also the 'cavalry', simultaneously optimizing on-board science return. Recently, however, most GRB science return has moved out from the gamma-ray energy bands where discovery usually occurs. Therefore a future gamma-ray instrument that is only a scout might best optimize future GRB science. Such a scout would specialize solely in the initial discovery of GRBs, determining only those properties that would allow an unambiguous handoff to waiting cavalry instruments. Preliminary general principles of scout design and cadence are discussed. Scouts could implement observing algorithms optimized for finding GRBs with specific attributes of duration, location, or energy. Scout sky-scanning algorithms utilizing a return cadence near to desired durations of short GRBs are suggested as a method of discovering GRBs in the unexplored short duration part of the GRB duration distribution

  14. Lifting Transit Signals from the Kepler Noise Floor. I. Discovery of a Warm Neptune

    Science.gov (United States)

    Kunimoto, Michelle; Matthews, Jaymie M.; Rowe, Jason F.; Hoffman, Kelsey

    2018-01-01

    Light curves from the 4-year Kepler exoplanet hunting mission have been searched for transits by NASA’s Kepler team and others, but there are still important discoveries to be made. We have searched the light curves of 400 Kepler Objects of Interest (KOIs) to find transit signals down to signal-to-noise ratio (S/N) ∼ 6, which is under the limit of S/N ∼ 7.1 that has been commonly adopted as a strict threshold to distinguish between a transit candidate and false alarm. We detect four new and convincing planet candidates ranging in radius from near-Mercury-size to slightly larger than Neptune. We highlight the discovery of KOI-408.05 (period = 637 days; radius = 4.9 R ⊕ incident flux = 0.6 S ⊕), a planet candidate within its host star’s Habitable Zone. We dub this planet a “warm Neptune,” a likely volatile-rich world that deserves closer inspection. KOI-408.05 joins 21 other confirmed and candidate planets in the current Kepler sample with semimajor axes a > 1.4 au. These discoveries are significant as a demonstration that the S/N threshold for detection used by the Kepler project is open to debate.

  15. 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

  16. Psychoactive drugs and false memory: comparison of dextroamphetamine and delta-9-tetrahydrocannabinol on false recognition

    Science.gov (United States)

    Ballard, Michael E.; Gallo, David A.; de Wit, Harriet

    2014-01-01

    Rationale Several psychoactive drugs are known to influence episodic memory. However, these drugs’ effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Objectives Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ9-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger–McDermott (DRM) illusion. Methods Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. Results As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs’ effects on true memory were positively correlated with their effects on false memory. Conclusions Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories. PMID:21647577

  17. Psychoactive drugs and false memory: comparison of dextroamphetamine and δ-9-tetrahydrocannabinol on false recognition.

    Science.gov (United States)

    Ballard, Michael E; Gallo, David A; de Wit, Harriet

    2012-01-01

    Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ(9)-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger-McDermott (DRM) illusion. Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs' effects on true memory were positively correlated with their effects on false memory. Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories.

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

    Science.gov (United States)

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

    2017-04-20

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

  19. SV-AUTOPILOT: optimized, automated construction of structural variation discovery and benchmarking pipelines.

    Science.gov (United States)

    Leung, Wai Yi; Marschall, Tobias; Paudel, Yogesh; Falquet, Laurent; Mei, Hailiang; Schönhuth, Alexander; Maoz Moss, Tiffanie Yael

    2015-03-25

    Many tools exist to predict structural variants (SVs), utilizing a variety of algorithms. However, they have largely been developed and tested on human germline or somatic (e.g. cancer) variation. It seems appropriate to exploit this wealth of technology available for humans also for other species. Objectives of this work included: a) Creating an automated, standardized pipeline for SV prediction. b) Identifying the best tool(s) for SV prediction through benchmarking. c) Providing a statistically sound method for merging SV calls. The SV-AUTOPILOT meta-tool platform is an automated pipeline for standardization of SV prediction and SV tool development in paired-end next-generation sequencing (NGS) analysis. SV-AUTOPILOT comes in the form of a virtual machine, which includes all datasets, tools and algorithms presented here. The virtual machine easily allows one to add, replace and update genomes, SV callers and post-processing routines and therefore provides an easy, out-of-the-box environment for complex SV discovery tasks. SV-AUTOPILOT was used to make a direct comparison between 7 popular SV tools on the Arabidopsis thaliana genome using the Landsberg (Ler) ecotype as a standardized dataset. Recall and precision measurements suggest that Pindel and Clever were the most adaptable to this dataset across all size ranges while Delly performed well for SVs larger than 250 nucleotides. A novel, statistically-sound merging process, which can control the false discovery rate, reduced the false positive rate on the Arabidopsis benchmark dataset used here by >60%. SV-AUTOPILOT provides a meta-tool platform for future SV tool development and the benchmarking of tools on other genomes using a standardized pipeline. It optimizes detection of SVs in non-human genomes using statistically robust merging. The benchmarking in this study has demonstrated the power of 7 different SV tools for analyzing different size classes and types of structural variants. The optional merge

  20. THE IMPACT OF EGO-INVOLVEMENT IN THE CREATION OF FALSE CHILDHOOD MEMORIES

    Directory of Open Access Journals (Sweden)

    Iris Zezelj

    2009-09-01

    Full Text Available An experiment employed a "familiar-informant false-narrative proce-dure" to examine the effects of ego involvement manipulation on the creation of false memories for suggested events. Our main sample consisted of 54 Serbian adolescent students. During the pre-testing stage, students’ parents (N=54 provided details from their children childhoods, which were used to create stimuli for the subsequent stages. Half of the participants were given an ego-involving suggestion- a short written statement that claimed that people with higher intelligence have a better and more detailed memory of their childhood. We hypothesized that ego-involved group would recollect more childhood events in general, create more false memories and be more confident in its’ authenticity and clarity. Implanted event was recognized as autobiographic by 24% respondents in the testing stage and by 44.4% respondents in the retesting stage. There were significant qualitative differences between authentic and false memories: authentic memories were assessed as more reliable and clearer than the false ones. Ego-involvement manipulation had no impact on the frequency or quality of false memories reported by the participants. Even though the specific ego-involvement manipulation was not successful, our findings suggest that other motivating strategies we employed pushed the respondents into accepting false memory suggestion in the retesting stage. Future research could benefit from testing more elaborate ego-involving procedures.

  1. Single nucleotide polymorphism discovery in rainbow trout by deep sequencing of a reduced representation library

    Directory of Open Access Journals (Sweden)

    Salem Mohamed

    2009-11-01

    Full Text Available Abstract Background To enhance capabilities for genomic analyses in rainbow trout, such as genomic selection, a large suite of polymorphic markers that are amenable to high-throughput genotyping protocols must be identified. Expressed Sequence Tags (ESTs have been used for single nucleotide polymorphism (SNP discovery in salmonids. In those strategies, the salmonid semi-tetraploid genomes often led to assemblies of paralogous sequences and therefore resulted in a high rate of false positive SNP identification. Sequencing genomic DNA using primers identified from ESTs proved to be an effective but time consuming methodology of SNP identification in rainbow trout, therefore not suitable for high throughput SNP discovery. In this study, we employed a high-throughput strategy that used pyrosequencing technology to generate data from a reduced representation library constructed with genomic DNA pooled from 96 unrelated rainbow trout that represent the National Center for Cool and Cold Water Aquaculture (NCCCWA broodstock population. Results The reduced representation library consisted of 440 bp fragments resulting from complete digestion with the restriction enzyme HaeIII; sequencing produced 2,000,000 reads providing an average 6 fold coverage of the estimated 150,000 unique genomic restriction fragments (300,000 fragment ends. Three independent data analyses identified 22,022 to 47,128 putative SNPs on 13,140 to 24,627 independent contigs. A set of 384 putative SNPs, randomly selected from the sets produced by the three analyses were genotyped on individual fish to determine the validation rate of putative SNPs among analyses, distinguish apparent SNPs that actually represent paralogous loci in the tetraploid genome, examine Mendelian segregation, and place the validated SNPs on the rainbow trout linkage map. Approximately 48% (183 of the putative SNPs were validated; 167 markers were successfully incorporated into the rainbow trout linkage map. In

  2. Single nucleotide polymorphism discovery in rainbow trout by deep sequencing of a reduced representation library.

    Science.gov (United States)

    Sánchez, Cecilia Castaño; Smith, Timothy P L; Wiedmann, Ralph T; Vallejo, Roger L; Salem, Mohamed; Yao, Jianbo; Rexroad, Caird E

    2009-11-25

    To enhance capabilities for genomic analyses in rainbow trout, such as genomic selection, a large suite of polymorphic markers that are amenable to high-throughput genotyping protocols must be identified. Expressed Sequence Tags (ESTs) have been used for single nucleotide polymorphism (SNP) discovery in salmonids. In those strategies, the salmonid semi-tetraploid genomes often led to assemblies of paralogous sequences and therefore resulted in a high rate of false positive SNP identification. Sequencing genomic DNA using primers identified from ESTs proved to be an effective but time consuming methodology of SNP identification in rainbow trout, therefore not suitable for high throughput SNP discovery. In this study, we employed a high-throughput strategy that used pyrosequencing technology to generate data from a reduced representation library constructed with genomic DNA pooled from 96 unrelated rainbow trout that represent the National Center for Cool and Cold Water Aquaculture (NCCCWA) broodstock population. The reduced representation library consisted of 440 bp fragments resulting from complete digestion with the restriction enzyme HaeIII; sequencing produced 2,000,000 reads providing an average 6 fold coverage of the estimated 150,000 unique genomic restriction fragments (300,000 fragment ends). Three independent data analyses identified 22,022 to 47,128 putative SNPs on 13,140 to 24,627 independent contigs. A set of 384 putative SNPs, randomly selected from the sets produced by the three analyses were genotyped on individual fish to determine the validation rate of putative SNPs among analyses, distinguish apparent SNPs that actually represent paralogous loci in the tetraploid genome, examine Mendelian segregation, and place the validated SNPs on the rainbow trout linkage map. Approximately 48% (183) of the putative SNPs were validated; 167 markers were successfully incorporated into the rainbow trout linkage map. In addition, 2% of the sequences from the

  3. Nonspecificity and theory of mind: new evidence from a nonverbal false-sign task and children with autism spectrum disorders.

    Science.gov (United States)

    Iao, Lai-Sang; Leekam, Susan R

    2014-06-01

    Understanding of false belief has long been considered to be a crucial aspect of "theory of mind" that can be explained by a domain-specific mechanism. We argue against this claim using new evidence from a nonverbal false representation task (false-sign task) with typically developing children and children with autism spectrum disorders (ASD). Experiments 1 and 2 showed that typically developing children (mean age=62.67months) were equivalent in their performance across nonverbal and verbal forms of both the false-belief and false-sign tasks. Results for these two misrepresentation tasks differed from the results of an outdated representation task ("false"-photograph task). Experiment 3 showed that children with ASD had difficulties with the false representation tasks, and this could not be explained by executive functioning or language impairments. These findings support the view that children with ASD might not have a specific theory-of-mind deficit. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Il nuovo reato di false comunicazioni sociali

    Directory of Open Access Journals (Sweden)

    Lorenzo Maria Corvucci

    2015-12-01

    Full Text Available The author examines the new offence of false social communication introduced by the Italian law dated 27 may 2015 n.69 in force from 14 June 2015. Considering the modifications added to the new offence of false accounting- basically explained to highlight the novum - the attention is paid on a specific major issue, previously discussed by the fifth section of the Italian Supreme Court competent in this matter after a few months from the moment the new law came in force. The questions applies to the fact whether the fraudulent evidence should remain to be punishable as the new discipline has limited the object of the criminal conduct only to “material relevant facts which are untrue” or to the omission of material relevant facts whose communication is imposed by the law regulating the economic situation, the assets and financial position of the company or of the group to which the company belongs. In this way any reference to the evaluations contained in the text previously in force is eliminated. Omissive conduct is the new definition recalling the two previous rules (art. 2621 and 2622 of the Italian civil code.

  5. Easy and Informative: Using Confidence-Weighted True-False Items for Knowledge Tests in Psychology Courses

    Science.gov (United States)

    Dutke, Stephan; Barenberg, Jonathan

    2015-01-01

    We introduce a specific type of item for knowledge tests, confidence-weighted true-false (CTF) items, and review experiences of its application in psychology courses. A CTF item is a statement about the learning content to which students respond whether the statement is true or false, and they rate their confidence level. Previous studies using…

  6. Discovery of massive neutral vector mesons

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

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

  7. Functional principles of registry-based service discovery

    NARCIS (Netherlands)

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

    2005-01-01

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

  8. Materials Discovery | Materials Science | NREL

    Science.gov (United States)

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

  9. On the pulse of discovery

    Science.gov (United States)

    2017-12-01

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

  10. Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data.

    Science.gov (United States)

    Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

    2013-05-01

    Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach.

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

    Science.gov (United States)

    Nsair, Ali; MacLellan, W Robb

    2011-04-30

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

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

    Science.gov (United States)

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

    2015-09-03

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

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

    Directory of Open Access Journals (Sweden)

    Chung-Ming Own

    2015-09-01

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

  14. Improved accuracy of cell surface shaving proteomics in Staphylococcus aureus using a false-positive control

    DEFF Research Database (Denmark)

    Solis, Nestor; Larsen, Martin Røssel; Cordwell, Stuart J

    2010-01-01

    Proteolytic treatment of intact bacterial cells is an ideal means for identifying surface-exposed peptide epitopes and has potential for the discovery of novel vaccine targets. Cell stability during such treatment, however, may become compromised and result in the release of intracellular proteins...... that complicate the final analysis. Staphylococcus aureus is a major human pathogen, causing community and hospital-acquired infections, and is a serious healthcare concern due to the increasing prevalence of multiple antibiotic resistances amongst clinical isolates. We employed a cell surface "shaving" technique...... to trypsin and three identified in the control. The use of a subtracted false-positive strategy improved enrichment of surface-exposed peptides in the trypsin data set to approximately 80% (124/155 peptides). Predominant surface proteins were those associated with methicillin resistance-surface protein SACOL...

  15. What Is False Memory Development the Development of? Comment on Brainerd, Reyna, and Ceci (2008)

    Science.gov (United States)

    Howe, Mark L.

    2008-01-01

    In this commentary, assumptions about the nature and development of children's false memories as described in a recent article by C. J. Brainerd, V. F. Reyna, and S. J. Ceci (2008) are reviewed. Specifically, questions are raised about what drives the development of false memories in fuzzy-trace theory (FTT). Recent studies that challenge a core…

  16. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases Summary

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

  17. [False positive results or what's the probability that a significant P-value indicates a true effect?

    Science.gov (United States)

    Cucherat, Michel; Laporte, Silvy

    2017-09-01

    The use of statistical test is central in the clinical trial. At the statistical level, obtaining a Pinformation about the plausibility of the existence of treatment effect. With "Pfalse positive is very high. This is the case if the power is low, if there is an inflation of the alpha risk or if the result is exploratory or chance discoveries. This possibility is important to take into consideration when interpreting the results of clinical trials in order to avoid pushing ahead significant results in appearance, but which are likely to be actually false positive results. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  18. Biomimicry as a basis for drug discovery.

    Science.gov (United States)

    Kolb, V M

    1998-01-01

    Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term "natural product" is often used synonymously with "secondary metabolite." Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed "inventive evolution." It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products ("unnatural natural products"), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.

  19. History, Discovery, and Classification of lncRNAs.

    Science.gov (United States)

    Jarroux, Julien; Morillon, Antonin; Pinskaya, Marina

    2017-01-01

    The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of

  20. Representing metarepresentations: is there theory of mind-specific cognition?

    Science.gov (United States)

    Egeth, Marc; Kurzban, Robert

    2009-03-01

    What cognitive mechanisms underlie Theory of Mind? Some infer domain-specific Theory of Mind cognition based the pattern of children diagnosed with autism failing the False Belief test but passing the False Photograph test. However, we argue that the False Belief test entails various task demands the False Photograph task does not, including the necessity to represent a higher-order representation (a metarepresentation), thus confounding the inference of domain-specificity. Instead, a general difficulty that affects representations of metarepresentations might account for the seeming domain-specific failure. Here we find that False-Belief failing False-Photograph passing children fail the Meta Photograph test, a new photograph-domain test that requires subjects to represent a metarepresentation. We conclude that people who fail the False Belief test but pass the False Photograph test do not necessarily have a content-specific Theory of Mind deficit. Instead, the general ability to represent representations and metarepresentations might underlie Theory of Mind.

  1. Gene-Specific Demethylation as Targeted Therapy in MDS

    Science.gov (United States)

    2017-07-01

    builds on our recent discovery of a novel class of RNAs, the DiRs or DNMT1-interacting RNAs, involved in cell type-specific DNA methylation patterns...causes leading to aberrant DNA methylation remain elusive. This proposal builds on our recent discovery of a novel class of RNAs, the DiRs or DNMT1...remains unknown. Our hypothesis is that the saRNAs might be acting as DiRs-mimicking molecules, and we will investigate whether saRNAs induce

  2. Service discovery using Bloom filters

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

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

  5. Implications of false-positive results for future cancer screenings.

    Science.gov (United States)

    Taksler, Glen B; Keating, Nancy L; Rothberg, Michael B

    2018-06-01

    False-positive cancer screening results may affect a patient's willingness to obtain future screening. The authors conducted logistic regression analysis of 450,484 person-years of electronic medical records (2006-2015) in 92,405 individuals aged 50 to 75 years. Exposures were false-positive breast, prostate, or colorectal cancer screening test results (repeat breast imaging or negative breast biopsy ≤3 months after screening mammography, repeat prostate-specific antigen [PSA] test ≤3 months after PSA test result ≥4.0 ng/mL or negative prostate biopsy ≤3 months after any PSA result, or negative colonoscopy [without biopsy/polypectomy] ≤6 months after a positive fecal occult blood test). Outcomes were up-to-date status with breast or colorectal cancer screening. Covariates included prior screening history, clinical information (eg, family history, obesity, and smoking status), comorbidity, and demographics. Women were more likely to be up to date with breast cancer screening if they previously had false-positive mammography findings (adjusted odds ratio [AOR], 1.43 [95% confidence interval, 1.34-1.51] without breast biopsy and AOR, 2.02 [95% confidence interval, 1.56-2.62] with breast biopsy; both Pfalse-positive PSA testing were more likely to be up to date with colorectal cancer screening (AOR, 1.22 [P = .039] without prostate imaging/biopsy and AOR, 1.60 [P = .028] with imaging/biopsy). Results were stronger for individuals with more false-positive results (all P≤.005). However, women with previous false-positive colorectal cancer fecal occult blood test screening results were found to be less likely to be up to date with breast cancer screening (AOR, 0.73; Pfalse-positive breast or prostate cancer screening test were more likely to engage in future screening. Cancer 2018;124:2390-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

  6. Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

    Science.gov (United States)

    Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

    2009-02-01

    Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

  7. Risk factors for false positive and for false negative test results in screening with fecal occult blood testing

    NARCIS (Netherlands)

    Stegeman, Inge; de Wijkerslooth, Thomas R.; Stoop, Esther M.; van Leerdam, Monique; van Ballegooijen, M.; Kraaijenhagen, Roderik A.; Fockens, Paul; Kuipers, Ernst J.; Dekker, Evelien; Bossuyt, Patrick M.

    2013-01-01

    Differences in the risk of a false negative or a false positive fecal immunochemical test (FIT) across subgroups may affect optimal screening strategies. We evaluate whether subgroups are at increased risk of a false positive or a false negative FIT result, whether such variability in risk is

  8. Language, Cognitive Flexibility, and Explicit False Belief Understanding: Longitudinal Analysis in Typical Development and Specific Language Impairment

    Science.gov (United States)

    Farrant, Brad M.; Maybery, Murray T.; Fletcher, Janet

    2012-01-01

    The hypothesis that language plays a role in theory-of-mind (ToM) development is supported by a number of lines of evidence (e.g., H. Lohmann & M. Tomasello, 2003). The current study sought to further investigate the relations between maternal language input, memory for false sentential complements, cognitive flexibility, and the development of…

  9. Price discovery in a continuous-time setting

    DEFF Research Database (Denmark)

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

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

  10. Defining Creativity with Discovery

    OpenAIRE

    Wilson, Nicholas Charles; Martin, Lee

    2017-01-01

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

  11. On the antiproton discovery

    International Nuclear Information System (INIS)

    Piccioni, O.

    1989-01-01

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

  12. 43 CFR 4.826 - Discovery.

    Science.gov (United States)

    2010-10-01

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

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

    Science.gov (United States)

    Dalal, Nikunj

    2012-01-01

    We describe the use of rapid game prototyping as a pedagogic technique to experientially explore and learn requirements discovery, modeling, and specification in systems analysis and design courses. Students have a natural interest in gaming that transcends age, gender, and background. Rapid digital game creation is used to build computer games…

  14. Is the truth in the details? Extended narratives help distinguishing false "memories" from false "reports".

    Science.gov (United States)

    Sjödén, Björn; Granhag, Pär Anders; Ost, James; Roos Af Hjelmsäter, Emma

    2009-06-01

    The present study examined the effects of fantasy proneness on false "reports" and false "memories", of existent and non-existent footage of a public event. We predicted that highly fantasy prone individuals would be more likely to stand by their initial claim of having seen a film of the event than low fantasy prone participants when prompted for more details about their experiences. Eighty creative arts students and 80 other students were asked whether they had seen CCTV footage preceding the attack on Swedish foreign minister Anna Lindh up to, and including, non-existent footage of the actual moment of the attack. If affirmative, they were probed for extended narratives of what they claimed to have seen. Overall, 64% of participants provided a false "report" by answering yes to the initial question. Of these, 30% provided no explicit details of the attack, and a further 15% retracted their initial answer in their narratives. This left 19% of the sample who appeared to have false "memories" because they provided explicit details of the actual moment of the attack. Women scored higher than men and art students scored higher than other students on fantasy proneness, but there was no effect on levels of false reporting or false "memory". Memories were rated more vivid and clear for existent compared to non-existent aspects of the event. In sum, these data suggest a more complex relationship between memory distortions and fantasy proneness than previously observed.

  15. Drug design and discovery: translational biomedical science varies among countries.

    Science.gov (United States)

    Weaver, Ian N; Weaver, Donald F

    2013-10-01

    Drug design and discovery is an innovation process that translates the outcomes of fundamental biomedical research into therapeutics that are ultimately made available to people with medical disorders in many countries throughout the world. To identify which nations succeed, exceed, or fail at the drug design/discovery endeavor--more specifically, which countries, within the context of their national size and wealth, are "pulling their weight" when it comes to developing medications targeting the myriad of diseases that afflict humankind--we compiled and analyzed a comprehensive survey of all new drugs (small molecular entities and biologics) approved annually throughout the world over the 20-year period from 1991 to 2010. Based upon this analysis, we have devised prediction algorithms to ascertain which countries are successful (or not) in contributing to the worldwide need for effective new therapeutics. © 2013 Wiley Periodicals, Inc.

  16. Resource-estimation models and predicted discovery

    International Nuclear Information System (INIS)

    Hill, G.W.

    1982-01-01

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

  17. Discovery and progress of direct cardiac reprogramming.

    Science.gov (United States)

    Kojima, Hidenori; Ieda, Masaki

    2017-06-01

    Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

  18. Automated discovery systems and the inductivist controversy

    Science.gov (United States)

    Giza, Piotr

    2017-09-01

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

  19. Malaria rapid diagnostic tests: Plasmodium falciparum infections with high parasite densities may generate false positive Plasmodium vivax pLDH lines

    Directory of Open Access Journals (Sweden)

    van Esbroeck Marjan

    2010-07-01

    Full Text Available Abstract Background Most malaria rapid diagnostic tests (RDTs detect Plasmodium falciparum and an antigen common to the four species. Plasmodium vivax-specific RDTs target P. vivax-specific parasite lactate dehydrogenase (Pv-pLDH. Previous observations of false positive Pv-pLDH test lines in P. falciparum samples incited to the present study, which assessed P. vivax-specific RDTs for the occurrence of false positive Pv-pLDH lines in P. falciparum samples. Methods Nine P. vivax-specific RDTs were tested with 85 P. falciparum samples of high (≥2% parasite density. Mixed P. falciparum/P. vivax infections were ruled out by real-time PCR. The RDTs included two-band (detecting Pv-pLDH, three-band (detecting P. falciparum-antigen and Pv-pLDH and four-band RDTs (detecting P. falciparum, Pv-pLDH and pan-pLDH. Results False positive Pv-pLDH lines were observed in 6/9 RDTs (including two- three- and four-band RDTs. They occurred in the individual RDT brands at frequencies ranging from 8.2% to 29.1%. For 19/85 samples, at least two RDT brands generated a false positive Pv-pLDH line. Sixteen of 85 (18.8% false positive lines were of medium or strong line intensity. There was no significant relation between false positive results and parasite density or geographic origin of the samples. Conclusion False positive Pv-pLDH lines in P. falciparum samples with high parasite density occurred in 6/9 P. vivax-specific RDTs. This is of concern as P. falciparum and P. vivax are co-circulating in many regions. The diagnosis of life-threatening P. falciparum malaria may be missed (two-band Pv-pLDH RDT, or the patient may be treated incorrectly with primaquine (three- or four-band RDTs.

  20. Blind sequential lineup administration reduces both false identifications and confidence in those false identifications.

    Science.gov (United States)

    Charman, Steve D; Quiroz, Vanessa

    2016-10-01

    One of the most recommended procedures proposed by eyewitness experts is the use of double-blind lineups, in which the administrator does not know the identity of the suspect in the lineup. But despite the near universality of this recommendation, there is surprisingly little empirical research to support the claim that nonblind administration inflates false identifications. What little research has been conducted has shown conflicting findings with regard to the conditions under which nonblind administration affects false identifications, as well as its effects on witness confidence. The current study attempts to elucidate this effect. Student-participants (n = 312) were randomly assigned to play the role of either a lineup administrator (who were either told the identity of the suspect in the lineup or not) or a mock crime witness. Following unbiased instructions, administrators presented either a target-present or target-absent sequential lineup to the witness while being surreptitiously videorecorded. Nonblind administration significantly inflated false, but not correct, identifications, and significantly inflated witness confidence in those false identifications. Video recordings indicated that nonblind administrators were significantly more likely than blind administrators to smile (a) while the witness was viewing a photograph of the suspect, and (b) after a suspect identification. Results provide stronger support for the use of blind lineup administration by broadening the conditions under which nonblind administration is shown to inflate false identifications. Possible reconciliations for conflicting findings in the literature are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Discovery of charm

    International Nuclear Information System (INIS)

    Goldhaber, G.

    1984-11-01

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

  2. 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.

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

    Science.gov (United States)

    Lømo, Terje

    2016-01-01

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

  4. Impact of kiln thermal energy demand and false air on cement kiln flue gas CO2 capture

    Energy Technology Data Exchange (ETDEWEB)

    Arachchige, Udara S.P.R.; Kawan, Dinesh; Tokheim, Lars-Andre [Telemark University College, Porsgrunn (Norway); Melaaen, Morten C. [Telemark University College, Porsgrunn (Norway); (Tel-Tek, Porsgrunn (Norway)

    2013-07-01

    The present study is focused on the effect of the specific thermal energy demand and the false air factor on carbon capture applied to cement kiln exhaust gases. The carbon capture process model was developed and implemented in Aspen Plus. The model was developed for flue gases from a typical cement clinker manufacturing plant. The specific thermal energy demand as well as the false air factor of the kiln system were varied in order to determine the effect on CO2 capture plant performance, such as the solvent regeneration energy demand. In general, an increase in the mentioned kiln system factors increases the regeneration energy demand. The reboiler energy demand is calculated as 3270, 3428 and 3589 kJ/kg clinker for a specific thermal energy of 3000, 3400 and 3800 kJ/kg clinker, respectively. Setting the false air factor to 25, 50 or 70% gives a reboiler energy demand of 3428, 3476, 3568 kJ/kg clinker, respectively.

  5. Metabolomics for Biomarker Discovery: Moving to the Clinic

    Science.gov (United States)

    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

  6. 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.

  7. Discovery of the leinamycin family of natural products by mining actinobacterial genomes.

    Science.gov (United States)

    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.

  8. Bioinformatics in translational drug discovery.

    Science.gov (United States)

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

    2017-08-31

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

  9. Discovery and therapeutic promise of selective androgen receptor modulators.

    Science.gov (United States)

    Chen, Jiyun; Kim, Juhyun; Dalton, James T

    2005-06-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

  10. Word type effects in false recall: concrete, abstract, and emotion word critical lures.

    Science.gov (United States)

    Bauer, Lisa M; Olheiser, Erik L; Altarriba, Jeanette; Landi, Nicole

    2009-01-01

    Previous research has demonstrated that definable qualities of verbal stimuli have implications for memory. For example, the distinction between concrete and abstract words has led to the finding that concrete words have an advantage in memory tasks (i.e., the concreteness effect). However, other word types, such as words that label specific human emotions, may also affect memory processes. This study examined the effects of word type on the production of false memories by using a list-learning false memory paradigm. Participants heard lists of words that were highly associated to nonpresented concrete, abstract, or emotion words (i.e., the critical lures) and then engaged in list recall. Emotion word critical lures were falsely recalled at a significantly higher rate (with the effect carried by the positively valenced critical lures) than concrete and abstract critical lures. These findings suggest that the word type variable has implications for our understanding of the mechanisms that underlie recall and false recall.

  11. SNP discovery in the bovine milk transcriptome using RNA-Seq technology.

    Science.gov (United States)

    Cánovas, Angela; Rincon, Gonzalo; Islas-Trejo, Alma; Wickramasinghe, Saumya; Medrano, Juan F

    2010-12-01

    High-throughput sequencing of RNA (RNA-Seq) was developed primarily to analyze global gene expression in different tissues. However, it also is an efficient way to discover coding SNPs. The objective of this study was to perform a SNP discovery analysis in the milk transcriptome using RNA-Seq. Seven milk samples from Holstein cows were analyzed by sequencing cDNAs using the Illumina Genome Analyzer system. We detected 19,175 genes expressed in milk samples corresponding to approximately 70% of the total number of genes analyzed. The SNP detection analysis revealed 100,734 SNPs in Holstein samples, and a large number of those corresponded to differences between the Holstein breed and the Hereford bovine genome assembly Btau4.0. The number of polymorphic SNPs within Holstein cows was 33,045. The accuracy of RNA-Seq SNP discovery was tested by comparing SNPs detected in a set of 42 candidate genes expressed in milk that had been resequenced earlier using Sanger sequencing technology. Seventy of 86 SNPs were detected using both RNA-Seq and Sanger sequencing technologies. The KASPar Genotyping System was used to validate unique SNPs found by RNA-Seq but not observed by Sanger technology. Our results confirm that analyzing the transcriptome using RNA-Seq technology is an efficient and cost-effective method to identify SNPs in transcribed regions. This study creates guidelines to maximize the accuracy of SNP discovery and prevention of false-positive SNP detection, and provides more than 33,000 SNPs located in coding regions of genes expressed during lactation that can be used to develop genotyping platforms to perform marker-trait association studies in Holstein cattle.

  12. Reduced False Memory after Sleep

    Science.gov (United States)

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  13. Coincidence of scintigraphic false positive and false negative findings in parathyroid and thyroid adenomas (case report)

    Energy Technology Data Exchange (ETDEWEB)

    Mana, O.; Zatta, G.; Boccolari, S.; Barbesti, S.; Tarolo, G.L.

    1987-04-01

    The subtractive double tracer scintigraphy with /sup 201/Tl and /sup 99m/Tc is a useful technique in studying parathyroid nodules; nevertheless, this method can give misleading informations especially in presence of thyroid nodules with false positive and false negative findings. In this case report the technique was applied in studying a patient with three nodules (two thyroid adenomas and one parathyroid adenoma), where both scintigraphic and echographic methods provided misleading informations. The selective uptake of /sup 201/Tl in the upper region of the right thyroid lobe gave a false positive finding, while the increased uptake of /sup 99m/Tc in a hyperfunctioning thyroid adenoma of left lobe masked the parathyroid adenoma laying below, giving a false negative finding.

  14. THE POSSIBLE MOON OF KEPLER-90g IS A FALSE POSITIVE

    Energy Technology Data Exchange (ETDEWEB)

    Kipping, D. M.; Torres, G.; Buchhave, L. A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Huang, X.; Bakos, G. Á. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 05844 (United States); Nesvorný, D. [Department of Space Studies, Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Schmitt, A. R., E-mail: dkipping@cfa.harvard.edu

    2015-01-20

    The discovery of an exomoon would provide deep insights into planet formation and the habitability of planetary systems, with transiting examples being particularly sought after. Of the hundreds of Kepler planets now discovered, the seven-planet system Kepler-90 is unusual for exhibiting an unidentified transit-like signal in close proximity to one of the transits of the long-period gas-giant Kepler-90g, as noted by Cabrera et al. As part of the ''Hunt for Exomoons with Kepler'' project, we investigate this possible exomoon signal and find it passes all conventional photometric, dynamical, and centroid diagnostic tests. However, pixel-level light curves indicate that the moon-like signal occurs on nearly all of the target's pixels, which we confirm using a novel way of examining pixel-level data which we dub the ''transit centroid''. This test reveals that the possible exomoon to Kepler-90g is likely a false positive, perhaps due to a cosmic ray induced sudden pixel sensitivity dropout. This work highlights the extreme care required for seeking non-periodic low-amplitude transit signals, such as exomoons.

  15. Shear-wave elastography in the diagnosis of solid breast masses: what leads to false-negative or false-positive results?

    Science.gov (United States)

    Yoon, Jung Hyun; Jung, Hae Kyoung; Lee, Jong Tae; Ko, Kyung Hee

    2013-09-01

    To investigate the factors that have an effect on false-positive or false-negative shear-wave elastography (SWE) results in solid breast masses. From June to December 2012, 222 breast lesions of 199 consecutive women (mean age: 45.3 ± 10.1 years; range, 21 to 88 years) who had been scheduled for biopsy or surgical excision were included. Greyscale ultrasound and SWE were performed in all women before biopsy. Final ultrasound assessments and SWE parameters (pattern classification and maximum elasticity) were recorded and compared with histopathology results. Patient and lesion factors in the 'true' and 'false' groups were compared. Of the 222 masses, 175 (78.8 %) were benign, and 47 (21.2 %) were malignant. False-positive rates of benign masses were significantly higher than false-negative rates of malignancy in SWE patterns, 36.6 % to 6.4 % (P masses, factors showing significance among false SWE features were lesion size, breast thickness and lesion depth (all P breast masses had SWE images of good quality. False SWE features were more significantly seen in benign masses. Lesion size, breast thickness and lesion depth have significance in producing false results, and this needs consideration in SWE image acquisition. • Shear-wave elastography (SWE) is widely used during breast imaging • At SWE, false-positive rates were significantly higher than false-negative rates • Larger size, breast thickness, depth and fair quality influences false-positive SWE features • Smaller size, larger breast thickness and depth influences false-negative SWE features.

  16. Prostate-Specific Antigen (PSA) Test

    Science.gov (United States)

    ... Cancer Prostate Cancer Screening Research Prostate-Specific Antigen (PSA) Test On This Page What is the PSA ... parts of the body before being detected. The PSA test may give false-positive or false-negative ...

  17. Arthritis Genetics Analysis Aids Drug Discovery

    Science.gov (United States)

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

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

    Science.gov (United States)

    Li, Yan; Kang, Congbao

    2017-08-23

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

  19. Statistics and Discoveries at the LHC (1/4)

    CERN Multimedia

    CERN. Geneva

    2010-01-01

    The lectures will give an introduction to statistics as applied in particle physics and will provide all the necessary basics for data analysis at the LHC. Special emphasis will be placed on the the problems and questions that arise when searching for new phenomena, including p-values, discovery significance, limit setting procedures, treatment of small signals in the presence of large backgrounds. Specific issues that will be addressed include the advantages and drawbacks of different statistical test procedures (cut-based, likelihood-ratio, etc.), the look-elsewhere effect and treatment of systematic uncertainties.

  20. Statistics and Discoveries at the LHC (3/4)

    CERN Multimedia

    CERN. Geneva

    2010-01-01

    The lectures will give an introduction to statistics as applied in particle physics and will provide all the necessary basics for data analysis at the LHC. Special emphasis will be placed on the the problems and questions that arise when searching for new phenomena, including p-values, discovery significance, limit setting procedures, treatment of small signals in the presence of large backgrounds. Specific issues that will be addressed include the advantages and drawbacks of different statistical test procedures (cut-based, likelihood-ratio, etc.), the look-elsewhere effect and treatment of systematic uncertainties.

  1. Statistics and Discoveries at the LHC (2/4)

    CERN Multimedia

    CERN. Geneva

    2010-01-01

    The lectures will give an introduction to statistics as applied in particle physics and will provide all the necessary basics for data analysis at the LHC. Special emphasis will be placed on the the problems and questions that arise when searching for new phenomena, including p-values, discovery significance, limit setting procedures, treatment of small signals in the presence of large backgrounds. Specific issues that will be addressed include the advantages and drawbacks of different statistical test procedures (cut-based, likelihood-ratio, etc.), the look-elsewhere effect and treatment of systematic uncertainties.

  2. Statistics and Discoveries at the LHC (4/4)

    CERN Multimedia

    CERN. Geneva

    2010-01-01

    The lectures will give an introduction to statistics as applied in particle physics and will provide all the necessary basics for data analysis at the LHC. Special emphasis will be placed on the the problems and questions that arise when searching for new phenomena, including p-values, discovery significance, limit setting procedures, treatment of small signals in the presence of large backgrounds. Specific issues that will be addressed include the advantages and drawbacks of different statistical test procedures (cut-based, likelihood-ratio, etc.), the look-elsewhere effect and treatment of systematic uncertainties.

  3. Developing a distributed HTML5-based search engine for geospatial resource discovery

    Science.gov (United States)

    ZHOU, N.; XIA, J.; Nebert, D.; Yang, C.; Gui, Z.; Liu, K.

    2013-12-01

    With explosive growth of data, Geospatial Cyberinfrastructure(GCI) components are developed to manage geospatial resources, such as data discovery and data publishing. However, the efficiency of geospatial resources discovery is still challenging in that: (1) existing GCIs are usually developed for users of specific domains. Users may have to visit a number of GCIs to find appropriate resources; (2) The complexity of decentralized network environment usually results in slow response and pool user experience; (3) Users who use different browsers and devices may have very different user experiences because of the diversity of front-end platforms (e.g. Silverlight, Flash or HTML). To address these issues, we developed a distributed and HTML5-based search engine. Specifically, (1)the search engine adopts a brokering approach to retrieve geospatial metadata from various and distributed GCIs; (2) the asynchronous record retrieval mode enhances the search performance and user interactivity; (3) the search engine based on HTML5 is able to provide unified access capabilities for users with different devices (e.g. tablet and smartphone).

  4. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. False Positives in Exoplanet Detection

    Science.gov (United States)

    Leuquire, Jacob; Kasper, David; Jang-Condell, Hannah; Kar, Aman; Sorber, Rebecca; Suhaimi, Afiq; KELT (Kilodegree Extremely Little Telescope)

    2018-06-01

    Our team at the University of Wyoming uses a 0.6 m telescope at RBO (Red Buttes Observatory) to help confirm results on potential exoplanet candidates from low resolution, wide field surveys shared by the KELT (Kilodegree Extremely Little Telescope) team. False positives are common in this work. We carry out transit photometry, and this method comes with special types of false positives. The most common false positive seen at the confirmation level is an EB (eclipsing binary). Low resolution images are great in detecting multiple sources for photometric dips in light curves, but they lack the precision to decipher single targets at an accurate level. For example, target star KC18C030621 needed RBO’s photometric precision to determine there was a nearby EB causing exoplanet type light curves. Identifying false positives with our telescope is important work because it helps eliminate the waste of time taken by more expensive telescopes trying to rule out negative candidate stars. It also furthers the identification of other types of photometric events, like eclipsing binaries, so they can be studied on their own.

  6. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    Issaq, Haleem J

    2013-01-01

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

  7. Discovery of the Higgs boson

    CERN Document Server

    Sharma, Vivek

    2016-01-01

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

  8. Price discovery in European natural gas markets

    International Nuclear Information System (INIS)

    Schultz, Emma; Swieringa, John

    2013-01-01

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

  9. Intraday Price Discovery in Fragmented Markets

    NARCIS (Netherlands)

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

    2014-01-01

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

  10. Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity

    Directory of Open Access Journals (Sweden)

    Charlotte Kürten

    2016-06-01

    Full Text Available The discovery and generation of biocatalysts with extended catalytic versatilities are of immense relevance in both chemistry and biotechnology. An enhanced atomistic understanding of enzyme promiscuity, a mechanism through which living systems acquire novel catalytic functions and specificities by evolution, would thus be of central interest. Using esterase-catalyzed amide bond hydrolysis as a model system, we pursued a simplistic in silico discovery program aiming for the identification of enzymes with an internal backbone hydrogen bond acceptor that could act as a reaction specificity shifter in hydrolytic enzymes. Focusing on stabilization of the rate limiting transition state of nitrogen inversion, our mechanism-guided approach predicted that the acyl hydrolase patatin of the α/β phospholipase fold would display reaction promiscuity. Experimental analysis confirmed previously unknown high amidase over esterase activity displayed by the first described esterase machinery with a protein backbone hydrogen bond acceptor to the reacting NH-group of amides. The present work highlights the importance of a fundamental understanding of enzymatic reactions and its potential for predicting enzyme scaffolds displaying alternative chemistries amenable to further evolution by enzyme engineering.

  11. Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

    Science.gov (United States)

    2015-01-01

    Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets. PMID:25189630

  12. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  13. A Taxonomy of Self-configuring Service Discovery Systems

    NARCIS (Netherlands)

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

    2007-01-01

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

  14. Discovery stories in the science classroom

    Science.gov (United States)

    Arya, Diana Jaleh

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

  15. Applied metabolomics in drug discovery.

    Science.gov (United States)

    Cuperlovic-Culf, M; Culf, A S

    2016-08-01

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

  16. False memory ≠ false memory: DRM errors are unrelated to the misinformation effect.

    Directory of Open Access Journals (Sweden)

    James Ost

    Full Text Available The DRM method has proved to be a popular and powerful, if controversial, way to study 'false memories'. One reason for the controversy is that the extent to which the DRM effect generalises to other kinds of memory error has been neither satisfactorily established nor subject to much empirical attention. In the present paper we contribute data to this ongoing debate. One hundred and twenty participants took part in a standard misinformation effect experiment, in which they watched some CCTV footage, were exposed to misleading post-event information about events depicted in the footage, and then completed free recall and recognition tests. Participants also completed a DRM test as an ostensibly unrelated filler task. Despite obtaining robust misinformation and DRM effects, there were no correlations between a broad range of misinformation and DRM effect measures (mean r  = -.01. This was not due to reliability issues with our measures or a lack of power. Thus DRM 'false memories' and misinformation effect 'false memories' do not appear to be equivalent.

  17. Predicting future discoveries from current scientific literature.

    Science.gov (United States)

    Petrič, Ingrid; Cestnik, Bojan

    2014-01-01

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

  18. A high content screening assay to predict human drug-induced liver injury during drug discovery.

    Science.gov (United States)

    Persson, Mikael; Løye, Anni F; Mow, Tomas; Hornberg, Jorrit J

    2013-01-01

    Adverse drug reactions are a major cause for failures of drug development programs, drug withdrawals and use restrictions. Early hazard identification and diligent risk avoidance strategies are therefore essential. For drug-induced liver injury (DILI), this is difficult using conventional safety testing. To reduce the risk for DILI, drug candidates with a high risk need to be identified and deselected. And, to produce drug candidates without that risk associated, risk factors need to be assessed early during drug discovery, such that lead series can be optimized on safety parameters. This requires methods that allow for medium-to-high throughput compound profiling and that generate quantitative results suitable to establish structure-activity-relationships during lead optimization programs. We present the validation of such a method, a novel high content screening assay based on six parameters (nuclei counts, nuclear area, plasma membrane integrity, lysosomal activity, mitochondrial membrane potential (MMP), and mitochondrial area) using ~100 drugs of which the clinical hepatotoxicity profile is known. We find that a 100-fold TI between the lowest toxic concentration and the therapeutic Cmax is optimal to classify compounds as hepatotoxic or non-hepatotoxic, based on the individual parameters. Most parameters have ~50% sensitivity and ~90% specificity. Drugs hitting ≥2 parameters at a concentration below 100-fold their Cmax are typically hepatotoxic, whereas non-hepatotoxic drugs typically hit based on nuclei count, MMP and human Cmax, we identified an area without a single false positive, while maintaining 45% sensitivity. Hierarchical clustering using the multi-parametric dataset roughly separates toxic from non-toxic compounds. We employ the assay in discovery projects to prioritize novel compound series during hit-to-lead, to steer away from a DILI risk during lead optimization, for risk assessment towards candidate selection and to provide guidance of safe

  19. Empirical methods for controlling false positives and estimating confidence in ChIP-Seq peaks

    Directory of Open Access Journals (Sweden)

    Courdy Samir J

    2008-12-01

    Full Text Available Abstract Background High throughput signature sequencing holds many promises, one of which is the ready identification of in vivo transcription factor binding sites, histone modifications, changes in chromatin structure and patterns of DNA methylation across entire genomes. In these experiments, chromatin immunoprecipitation is used to enrich for particular DNA sequences of interest and signature sequencing is used to map the regions to the genome (ChIP-Seq. Elucidation of these sites of DNA-protein binding/modification are proving instrumental in reconstructing networks of gene regulation and chromatin remodelling that direct development, response to cellular perturbation, and neoplastic transformation. Results Here we present a package of algorithms and software that makes use of control input data to reduce false positives and estimate confidence in ChIP-Seq peaks. Several different methods were compared using two simulated spike-in datasets. Use of control input data and a normalized difference score were found to more than double the recovery of ChIP-Seq peaks at a 5% false discovery rate (FDR. Moreover, both a binomial p-value/q-value and an empirical FDR were found to predict the true FDR within 2–3 fold and are more reliable estimators of confidence than a global Poisson p-value. These methods were then used to reanalyze Johnson et al.'s neuron-restrictive silencer factor (NRSF ChIP-Seq data without relying on extensive qPCR validated NRSF sites and the presence of NRSF binding motifs for setting thresholds. Conclusion The methods developed and tested here show considerable promise for reducing false positives and estimating confidence in ChIP-Seq data without any prior knowledge of the chIP target. They are part of a larger open source package freely available from http://useq.sourceforge.net/.

  20. Mandolin: A Knowledge Discovery Framework for the Web of Data

    OpenAIRE

    Soru, Tommaso; Esteves, Diego; Marx, Edgard; Ngomo, Axel-Cyrille Ngonga

    2017-01-01

    Markov Logic Networks join probabilistic modeling with first-order logic and have been shown to integrate well with the Semantic Web foundations. While several approaches have been devised to tackle the subproblems of rule mining, grounding, and inference, no comprehensive workflow has been proposed so far. In this paper, we fill this gap by introducing a framework called Mandolin, which implements a workflow for knowledge discovery specifically on RDF datasets. Our framework imports knowledg...

  1. Is it wise to protect false targets?

    International Nuclear Information System (INIS)

    Levitin, Gregory; Hausken, Kjell

    2011-01-01

    The paper considers a system consisting of genuine elements and false targets that cannot be distinguished by the attacker's observation. The false targets can be destroyed with much less effort than the genuine elements. We show that even when an attacker cannot distinguish between the genuine elements and the false targets, in many cases it can enhance the attack efficiency using a double attack strategy in which it tries first to eliminate with minimal effort as many false targets as possible in the first attack and then distributes its entire remaining resource among all surviving targets in the second attack. The model for evaluating the system vulnerability in the double attack is suggested for a single genuine element, and multiple genuine elements configured in parallel or in series. This model assumes that in both attacks the attacking resource is distributed evenly among the attacked targets. The defender can optimize its limited resource distribution between deploying more false targets and protecting them better. The attacker can optimize its limited resource distribution between two attacks. The defense strategy is analyzed based on a two period minmax game. A numerical procedure is suggested that allows the defender to find the optimal resource distribution between deploying and protecting the false targets. The methodology of optimal attack and defense strategies analysis is demonstrated. It is shown that protecting the false targets may reduce the efficiency of the double attack strategy and make this strategy ineffective in situations with low contest intensity and few false targets. - Highlights: ► The efficiency of the double attack tactics against using false targets is analyzed. ► The role of the false target protection in system survivability enhancement is shown. ► The resource distribution between deploying more false targets and protecting them better is optimized. ► Both series and parallel systems are considered.

  2. Fragment-based drug discovery and protein–protein interactions

    Directory of Open Access Journals (Sweden)

    Turnbull AP

    2014-09-01

    -dimensional character. These physiochemical properties can potentially be exploited in the rational design of PPI-specific fragment libraries and correlate well with optimized PPI inhibitors, which tend to have properties outside currently accepted guidelines for drug-likeness. Several examples of small-molecule PPI inhibitors derived from fragment-based drug discovery now exist and are described in this review, including navitoclax, a novel Bcl-2 family inhibitor which has entered Phase II clinical trials in patients with small-cell lung cancer and chronic lymphocytic leukemia.Keywords: hot spot, druggability, ligandability

  3. Mosquito-specific and mosquito-borne viruses: evolution, infection, and host defense

    NARCIS (Netherlands)

    Halbach, R.; Junglen, S.; Rij, R.P. van

    2017-01-01

    Recent virus discovery programs have identified an extensive reservoir of viruses in arthropods. It is thought that arthropod viruses, including mosquito-specific viruses, are ancestral to vertebrate-pathogenic arboviruses. Mosquito-specific viruses are restricted in vertebrate cells at multiple

  4. The neutron discovery

    International Nuclear Information System (INIS)

    Six, J.

    1987-01-01

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

  5. Viral pathogen discovery

    Science.gov (United States)

    Chiu, Charles Y

    2015-01-01

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

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

    Science.gov (United States)

    Cohen, Seth M

    2017-08-15

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

  7. SkyDiscovery: Humans and Machines Working Together

    Science.gov (United States)

    Donalek, Ciro; Fang, K.; Drake, A. J.; Djorgovski, S. G.; Graham, M. J.; Mahabal, A.; Williams, R.

    2011-01-01

    Synoptic sky surveys are now discovering tens to hundreds of transient events every clear night, and that data rate is expected to increase dramatically as we move towards the LSST. A key problem is classification of transients, which determines their scientific interest and possible follow-up. Some of the relevant information is contextual, and easily recognizable by humans looking at images, but it is very hard to encode in the data pipelines. Crowdsourcing (aka Citizen Science) provides one possible way to gather such information. SkyDiscovery.org is a website that allows experts and citizen science enthusiasts to work together and share information in a collaborative scientific discovery environment. Currently there are two projects running on the website. In the Event Classification project users help finding candidate transients through a series of questions related to the images shown. Event classification depends very much form the contextual information and humans are remarkably effective at recognizing noise in incomplete heterogeneous data and figuring out which contextual information is important. In the SNHunt project users are requested to look for new objects appearing on images of galaxies taken by the Catalina Real-time Transient Survey, in order to find all the supernovae occurring in nearby bright galaxies. Images are served alongside with other tools that can help the discovery. A multi level approach allows the complexity of the interface to be tailored to the expertise level of the user. An entry level user can just review images and validate events as being real, while a more advanced user would be able to interact with the data associated to an event. The data gathered will not be only analyzed and used directly for some specific science project, but also to train well-defined algorithms to be used in automating such data analysis in the future.

  8. True photographs and false memories.

    Science.gov (United States)

    Lindsay, D Stephen; Hagen, Lisa; Read, J Don; Wade, Kimberley A; Garry, Maryanne

    2004-03-01

    Some trauma-memory-oriented psychotherapists advise clients to review old family photo albums to cue suspected "repressed" memories of childhood sexual abuse. Old photos might cue long-forgotten memories, but when combined with other suggestive influences they might also contribute to false memories. We asked 45 undergraduates to work at remembering three school-related childhood events (two true events provided by parents and one pseudoevent). By random assignment, 23 subjects were also given their school classes' group photos from the years of the to-be-recalled events as memory cues. As predicted, the rate of false-memory reports was dramatically higher in the photo condition than in the no-photo condition. Indeed, the rate of false-memory reports in the photo condition was substantially higher than the rate in any previously published study.

  9. False-negative results of breast core needle biopsies - retrospective analysis of 988 biopsies

    International Nuclear Information System (INIS)

    Boba, M.; Koltun, U.; Bobek-Billewicz, B.; Eksner, B.; Olejnik, T.; Chmielik, E.

    2011-01-01

    Background: Breast cancer is the most common malignant neoplasm and the most common cause of death among women. The core needle biopsy is becoming a universal practice in diagnosing breast lesions suspected of malignancy. Unfortunately, breast core needle biopsies also bear the risk of having false-negative results. Material/Methods: 988 core needle breast biopsies were performed at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, between 01 March 2006 and 29 February 2008. Malignant lesions were diagnosed in 426/988 (43.12%) cases, atypical hyperplasia in 69/988 (6.98%), and benign lesions in 493/988 (49.90%) cases. Results: Twenty-two out of 988 biopsies (2.23%) were found to be false negative. Histopathological assessment of tissue specimens was repeated in these cases. In 14/22 (64%) cases, the previous diagnosis of a benign lesion was changed. In 8/22 (36%) cases, the diagnosis of a benign lesion was confirmed. False-negative rate was calculated at 2.2%. The rate of false-negative diagnoses resulting from a radiological mistake was estimated at 36%. The rate of false-negative diagnoses, resulting from histopathological assessment, was 64%. False-negative results caused by a radiological error comprised 1.5% of all histopathologically diagnosed cancers and atypias (sensitivity of 98.5%). There were no false-positive results in our material - the specificity of the method was 100%. Conclusions: Histopathological interpretation is a substantial cause of false-negative results of breast core needle biopsy. Thus, in case of a radiological-histopathological divergence, histopathological analysis of biopsy specimens should be repeated. The main radiological causes of false-negative results of breast core needle biopsy are as follows: sampling from an inappropriate site and histopathological non-homogeneity of cancer infiltration. (authors)

  10. Effects of Post-Encoding Stress on Performance in the DRM False Memory Paradigm

    Science.gov (United States)

    Pardilla-Delgado, Enmanuelle; Alger, Sara E.; Cunningham, Tony J.; Kinealy, Brian; Payne, Jessica D.

    2016-01-01

    Numerous studies have investigated how stress impacts veridical memory, but how stress influences false memory formation remains poorly understood. In order to target memory consolidation specifically, a psychosocial stress (TSST) or control manipulation was administered following encoding of 15 neutral, semantically related word lists (DRM false…

  11. Systemic True False

    African Journals Online (AJOL)

    Preferred Customer

    ):. (a). (b). (c). (d). Answer: True systemics are (b & c); False Systemics (a & d). For more examples, see (10 and 11). Na2O2. NaCl. Na. HCl heat /excess. (O). 300°C electrolysis. (molten). NaOH. NaCl. Na. HCl. H2O electrolysis. (solution). NaCl.

  12. Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

    Science.gov (United States)

    Tahara, Hideaki; Sato, Marimo; Thurin, Magdalena; Wang, Ena; Butterfield, Lisa H; Disis, Mary L; Fox, Bernard A; Lee, Peter P; Khleif, Samir N; Wigginton, Jon M; Ambs, Stefan; Akutsu, Yasunori; Chaussabel, Damien; Doki, Yuichiro; Eremin, Oleg; Fridman, Wolf Hervé; Hirohashi, Yoshihiko; Imai, Kohzoh; Jacobson, James; Jinushi, Masahisa; Kanamoto, Akira; Kashani-Sabet, Mohammed; Kato, Kazunori; Kawakami, Yutaka; Kirkwood, John M; Kleen, Thomas O; Lehmann, Paul V; Liotta, Lance; Lotze, Michael T; Maio, Michele; Malyguine, Anatoli; Masucci, Giuseppe; Matsubara, Hisahiro; Mayrand-Chung, Shawmarie; Nakamura, Kiminori; Nishikawa, Hiroyoshi; Palucka, A Karolina; Petricoin, Emanuel F; Pos, Zoltan; Ribas, Antoni; Rivoltini, Licia; Sato, Noriyuki; Shiku, Hiroshi; Slingluff, Craig L; Streicher, Howard; Stroncek, David F; Takeuchi, Hiroya; Toyota, Minoru; Wada, Hisashi; Wu, Xifeng; Wulfkuhle, Julia; Yaguchi, Tomonori; Zeskind, Benjamin; Zhao, Yingdong; Zocca, Mai-Britt; Marincola, Francesco M

    2009-01-01

    Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations. Converging concepts were identified: enhanced knowledge of interferon-related pathways was found to be central to the understanding of immune-mediated tissue-specific destruction (TSD) of which tumor rejection is a representative facet. Although the expression of interferon-stimulated genes (ISGs) likely mediates the inflammatory process leading to tumor rejection, it is insufficient by itself and the associated mechanisms need to be identified. It is likely that adaptive immune responses play a broader role in tumor rejection than those strictly related to their antigen-specificity; likely, their primary role is to trigger an acute and tissue-specific inflammatory response at the tumor site that leads to rejection upon recruitment of additional innate and adaptive immune mechanisms. Other candidate systemic and/or tissue-specific biomarkers were recognized that

  13. Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

    Directory of Open Access Journals (Sweden)

    Rivoltini Licia

    2009-06-01

    Full Text Available Abstract Supported by the Office of International Affairs, National Cancer Institute (NCI, the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc and the United States Food and Drug Administration (FDA to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations. Converging concepts were identified: enhanced knowledge of interferon-related pathways was found to be central to the understanding of immune-mediated tissue-specific destruction (TSD of which tumor rejection is a representative facet. Although the expression of interferon-stimulated genes (ISGs likely mediates the inflammatory process leading to tumor rejection, it is insufficient by itself and the associated mechanisms need to be identified. It is likely that adaptive immune responses play a broader role in tumor rejection than those strictly related to their antigen-specificity; likely, their primary role is to trigger an acute and tissue-specific inflammatory response at the tumor site that leads to rejection upon recruitment of additional innate and adaptive immune mechanisms. Other candidate systemic and/or tissue-specific biomarkers

  14. Predictors of timing of pregnancy discovery.

    Science.gov (United States)

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

    2018-04-01

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

  15. Book Review: Dispute Resolution and e-Discovery

    Directory of Open Access Journals (Sweden)

    Milton Luoma

    2012-09-01

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

  16. Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

    Directory of Open Access Journals (Sweden)

    Zomaya Albert Y

    2006-12-01

    Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

  17. The False Memory and the Mirror Effects: The Role of Familiarity and Backward Association in Creating False Recollections

    Science.gov (United States)

    Anaki, D.; Faran, Y.; Ben-Shalom, D.; Henik, A.

    2005-01-01

    The mirror effect refers to a phenomenon where the hit rate is higher for low frequency words while the false alarm rate is higher for high frequency distractors. Using a false memory paradigm (Roediger & McDermott, 1995), we examined whether false memory for non-presented lures would be influenced by the lure's familiarity. The results revealed…

  18. Harvest: a web-based biomedical data discovery and reporting application development platform.

    Science.gov (United States)

    Italia, Michael J; Pennington, Jeffrey W; Ruth, Byron; Wrazien, Stacey; Loutrel, Jennifer G; Crenshaw, E Bryan; Miller, Jeffrey; White, Peter S

    2013-01-01

    Biomedical researchers share a common challenge of making complex data understandable and accessible. This need is increasingly acute as investigators seek opportunities for discovery amidst an exponential growth in the volume and complexity of laboratory and clinical data. To address this need, we developed Harvest, an open source framework that provides a set of modular components to aid the rapid development and deployment of custom data discovery software applications. Harvest incorporates visual representations of multidimensional data types in an intuitive, web-based interface that promotes a real-time, iterative approach to exploring complex clinical and experimental data. The Harvest architecture capitalizes on standards-based, open source technologies to address multiple functional needs critical to a research and development environment, including domain-specific data modeling, abstraction of complex data models, and a customizable web client.

  19. Newly formed skeletal muscle fibers are prone to false positive immunostaining by rabbit antibodies

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Kliem, Anette; Schrøder, Henrik Daa

    2011-01-01

    rely on controls that reveal non-specific binding by the secondary antibody and neglect that the primary rabbit antibody itself may cause false positive staining of the muscle. We suggest that reliable immuno-based protein detection in newly formed muscle fibers at least requires a nonsense rabbit......Reports on muscle biology and regeneration often implicate immuno(cyto/histo)chemical protein characterization using rabbit polyclonal antibodies. In this study we demonstrate that newly formed myofibers are especially prone to false positive staining by rabbit antibodies and this unwanted staining...

  20. Proteomic Biomarker Discovery in 1000 Human Plasma Samples with Mass Spectrometry.

    Science.gov (United States)

    Cominetti, Ornella; Núñez Galindo, Antonio; Corthésy, John; Oller Moreno, Sergio; Irincheeva, Irina; Valsesia, Armand; Astrup, Arne; Saris, Wim H M; Hager, Jörg; Kussmann, Martin; Dayon, Loïc

    2016-02-05

    The overall impact of proteomics on clinical research and its translation has lagged behind expectations. One recognized caveat is the limited size (subject numbers) of (pre)clinical studies performed at the discovery stage, the findings of which fail to be replicated in larger verification/validation trials. Compromised study designs and insufficient statistical power are consequences of the to-date still limited capacity of mass spectrometry (MS)-based workflows to handle large numbers of samples in a realistic time frame, while delivering comprehensive proteome coverages. We developed a highly 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 the quality of the MS data and provided descriptive statistics. The data set was interrogated for proteins with most stable expression levels in that set of plasma samples. We evaluated standard clinical variables that typically impact forthcoming results and assessed body mass index-associated and gender-specific proteins at two time points. We demonstrate that analyzing a large number of human plasma samples for biomarker discovery with MS using isobaric tagging is feasible, providing robust and consistent biological results.

  1. Development of SCAR marker specific to non-toxic Jatropha curcas L. and designing a novel multiplexing PCR along with nrDNA ITS primers to circumvent the false negative detection

    KAUST Repository

    Mastan, Shaik G.

    2011-05-10

    Jatropha curcas L., a multipurpose shrub, has acquired significant economic importance for its seed oil which can be converted to biodiesel an emerging alternative to petro-diesel. In addition to the commercial value, it is also having medicinal and even high nutritional value to use as animal fodder which is limited due to the toxicity. Development of molecular marker will enable to differentiate non-toxic from toxic variety of J. curcas in a mixed population and also for quality control since the toxic components of J. curcas has deleterious effect on animals. In the present study, the efforts were made to generate the specific SCAR marker for toxic and/or non-toxic J. curcas from RAPD markers. Among the markers specific for toxic and non-toxic varieties, four were selected, purified, cloned, sequenced, and designed primers out of which one set of primers NT-JC/SCAR I/OPQ15-F and R could able to discriminate the non-toxic with toxic Jatropha by giving expected 430 bp size amplification in non-toxic variety. Furthermore, novel multiplex PCR was designed using the nrDNA ITS primers to overcome the false negatives. Present work also demonstrates utility of the conserved regions of nrDNA coding genes in ruling out the artifacts in PCR-like false negatives frequently occur in SCAR due to various reasons. The specific SCAR markers generated in the present investigation will help to distinguish non-toxic from toxic varieties of J. curcas or vice versa, and isolated marker along with designed multiplex protocol has applications in quality control for selective cultivation of non-toxic variety and will also assist in breeding and molecular mapping studies. © 2011 Springer Science+Business Media, LLC.

  2. Sleep loss produces false memories.

    Directory of Open Access Journals (Sweden)

    Susanne Diekelmann

    Full Text Available People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",..., lacking the strongest common associate or theme word (here: "black". Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.

  3. Bayesian Modeling of Temporal Coherence in Videos for Entity Discovery and Summarization.

    Science.gov (United States)

    Mitra, Adway; Biswas, Soma; Bhattacharyya, Chiranjib

    2017-03-01

    A video is understood by users in terms of entities present in it. Entity Discovery is the task of building appearance model for each entity (e.g., a person), and finding all its occurrences in the video. We represent a video as a sequence of tracklets, each spanning 10-20 frames, and associated with one entity. We pose Entity Discovery as tracklet clustering, and approach it by leveraging Temporal Coherence (TC): the property that temporally neighboring tracklets are likely to be associated with the same entity. Our major contributions are the first Bayesian nonparametric models for TC at tracklet-level. We extend Chinese Restaurant Process (CRP) to TC-CRP, and further to Temporally Coherent Chinese Restaurant Franchise (TC-CRF) to jointly model entities and temporal segments using mixture components and sparse distributions. For discovering persons in TV serial videos without meta-data like scripts, these methods show considerable improvement over state-of-the-art approaches to tracklet clustering in terms of clustering accuracy, cluster purity and entity coverage. The proposed methods can perform online tracklet clustering on streaming videos unlike existing approaches, and can automatically reject false tracklets. Finally we discuss entity-driven video summarization- where temporal segments of the video are selected based on the discovered entities, to create a semantically meaningful summary.

  4. False-negative syphilis treponemal enzyme immunoassay results in an HIV-infected case-patient.

    Science.gov (United States)

    Katz, Alan R; Komeya, Alan Y; Tomas, Juval E

    2017-06-01

    We present a case report of a false-negative syphilis treponemal enzyme immunoassay test result in an HIV-infected male. While treponemal tests are widely considered to be more sensitive and specific than non-treponemal tests, our findings point to potential challenges using the reverse sequence syphilis screening algorithm.

  5. False memories in social anxiety disorder

    Directory of Open Access Journals (Sweden)

    PRISCILA DE CAMARGO PALMA

    Full Text Available Abstract Background False memories are memories of events that never occurred or that occurred, but not exactly as we recall. Events with emotional content are subject to false memories production similar to neutral events. However, individual differences, such as the level of maladjustment and emotional instability characteristics of Social Anxiety Disorder (SAD, may interfere in the production of false memories. Objectives This study aimed to assess the effect of emotion in memory performance for an event witnessed by participants with and without SAD. Methods Participants were 61 young adults with SAD and 76 without any symptoms of SAD who were randomly assigned to watch a story with or without emotional arousal. Participants answered a subjective scale of emotion about the story and a recognition memory test. Results Participants with SAD recovered more true memories and more false memories for the non-emotional version compared to the emotional version of the story. Overall, participants with SAD produced fewer false memories compared to those without SAD. Discussion This finding suggests that social anxiety may have a significant impact on emotional memory accuracy, which may assist in the development and improvement of techniques for therapeutic intervention.

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

    Science.gov (United States)

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

    2017-11-27

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

  7. Attitude Importance and the False Consensus Effect.

    Science.gov (United States)

    Fabrigar, Leandre R.; Krosnick, Jon A.

    1995-01-01

    Explores the possibility that importance may regulate the magnitude of the false consensus effect. Analysis revealed a strong false consensus effect but no reliable relation between its magnitude and attitude importance. Results contradict assumptions that the false consensus effect arises from attitudes that directly or indirectly influence…

  8. Limits to Arbitrage in Sovereign Bonds Price and Liquidity Discovery in High Frequency Quote Driven Markets

    DEFF Research Database (Denmark)

    Pelizzon, Loriana; Subrahmanyam, Marti G.; Tomio, Davide

    The progressively stronger linkages across markets, due to faster access to information and trade execution, cause market liquidity to be rapidly transmitted across markets. In contrast to the resultant commonality of liquidity across markets that are affected by common market-wide factors...... between markets, and liquidity discovery, the transmission of liquidity shocks, through changes in the quotes posted by market makers and the reactions of arbitrageurs. Our analysis is in the context of the Italian sovereign bond cash and future markets, during the recent Euro-zone sovereign bond crisis...... discovery, the cash market leads the futures market in liquidity discovery, i.e., the willingness of the market makers to trade (measured by market depth as the key liquidity measure). More specifically, the liquidity in the cash market also has a significant impact on the changes in the basis (and...

  9. Providing data science support for systems pharmacology and its implications to drug discovery.

    Science.gov (United States)

    Hart, Thomas; Xie, Lei

    2016-01-01

    The conventional one-drug-one-target-one-disease drug discovery process has been less successful in tracking multi-genic, multi-faceted complex diseases. Systems pharmacology has emerged as a new discipline to tackle the current challenges in drug discovery. The goal of systems pharmacology is to transform huge, heterogeneous, and dynamic biological and clinical data into interpretable and actionable mechanistic models for decision making in drug discovery and patient treatment. Thus, big data technology and data science will play an essential role in systems pharmacology. This paper critically reviews the impact of three fundamental concepts of data science on systems pharmacology: similarity inference, overfitting avoidance, and disentangling causality from correlation. The authors then discuss recent advances and future directions in applying the three concepts of data science to drug discovery, with a focus on proteome-wide context-specific quantitative drug target deconvolution and personalized adverse drug reaction prediction. Data science will facilitate reducing the complexity of systems pharmacology modeling, detecting hidden correlations between complex data sets, and distinguishing causation from correlation. The power of data science can only be fully realized when integrated with mechanism-based multi-scale modeling that explicitly takes into account the hierarchical organization of biological systems from nucleic acid to proteins, to molecular interaction networks, to cells, to tissues, to patients, and to populations.

  10. Current management of inguinal false aneurysms

    DEFF Research Database (Denmark)

    Houlind, Kim; Jepsen, Jørn M; Saicu, Cristian

    2017-01-01

    False aneurysms are formed as a result of bleeding causing a hematoma to compress the surrounding tissue. The majority of false aneurysms presenting to the vascular surgeon are caused by iatrogenic injury to an artery. Although anastomotic failure occurs, a much higher number is caused by bleeding...... vessels. endovascular treatment with coils or covered stent grafts have proven useful in infected ilio-femoral false aneurysms. Open surgical repair may be the best treatment in the setting of imminent rupture, massive haematoma and skin necrosis. We present three patient cases treated with open surgery...

  11. Discovery of centrosomal RNA and centrosomal hypothesis of cellular ageing and differentiation.

    Science.gov (United States)

    Chichinadze, Konstantin; Tkemaladze, Jaba; Lazarashvili, Ann

    2012-01-01

    In 2006, a group of scientists studying centrosomes of Spisula solidissima mollusc oocytes under the leadership of Alliegro (Alliegro, M.C.; Alliegro, M.A.; Palazzo, R.E. Centrosome-associated RNA in surf clam oocytes. Proc. Natl. Acad. Sci. USA 2006, 103(24), 9034-9038) reliably demonstrated the existence of specific RNA in centrosome, called centrosomal RNA (cnRNA). In their first article, five different RNAs (cnRNAs 11, 102, 113, 170, and 184) were described. During the process of full sequencing of the first transcript (cnRNA 11), it was discovered that the transcript contained a conserved structure-a reverse transcriptase domain located together with the most important centrosomal protein, γ-tubulin. In an article published in 2005, we made assumptions about several possible mechanisms for determining the most important functions of centrosomal structures and referred to one of them as a "RNA-dependent mechanism." This idea about participation of hypothetic centrosomal small interference RNA and/or microRNA in the process was made one year prior to the discovery of cnRNA by Alliegro's group. The discovery of specific RNA in a centrosome is indirect evidence of a centrosomal hypothesis of cellular ageing and differentiation. The presence of a reverse transcriptase domain in this type of RNA, together with its uniqueness and specificity, makes the centrosome a place of information storage and reproduction.

  12. 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...

  13. Arrayed antibody library technology for therapeutic biologic discovery.

    Science.gov (United States)

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

    2013-03-15

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

  14. A critical reappraisal of false negative sentinel lymph node biopsy in melanoma

    International Nuclear Information System (INIS)

    Manca, G.; Mazzarri, S.; Boni, G.; Chiacchio, S.; Tredici, M.; Duce, V.; Tardelli, E.; Volterrani, D.; Mariani, G.; Romanini, A.; Rubello, D.

    2014-01-01

    prognosis of melanoma patients. Indeed, most studies have failed to show that there is worse melanoma-specific survival for false-negative compared to true-positive SLNB patient

  15. Elevated false recognition in patients with frontal lobe damage is neither a general nor a unitary phenomenon.

    Science.gov (United States)

    Verfaellie, Mieke; Rapcsak, Steven Z; Keane, Margaret M; Alexander, Michael P

    2004-01-01

    This study examined verbal recognition memory in amnesic patients with frontal lesions (AF), nonamnesic patients with frontal lesions (NAF), and amnesic patients with medial temporal lesions (MT). To examine susceptibility to false alarms, the number of studied words drawn from various categories was varied. The AF and MT groups demonstrated reduced hits and increased false alarms. False alarms were especially elevated when item-specific recollection was strongest in control participants. The NAF group performed indistinguishably from control participants, but several patients showed excessive false alarms in the context of normal hit rates. These patients exhibited impaired monitoring and verification processes. The findings demonstrate that elevated false recognition is not characteristic of all frontal patients and may result from more than 1 underlying mechanism. ((c) 2004 APA, all rights reserved)

  16. Radioactivity. Centenary of radioactivity discovery

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  17. Predicting Causal Relationships from Biological Data: Applying Automated Casual Discovery on Mass Cytometry Data of Human Immune Cells

    KAUST Repository

    Triantafillou, Sofia; Lagani, Vincenzo; Heinze-Deml, Christina; Schmidt, Angelika; Tegner, Jesper; Tsamardinos, Ioannis

    2017-01-01

    Learning the causal relationships that define a molecular system allows us to predict how the system will respond to different interventions. Distinguishing causality from mere association typically requires randomized experiments. Methods for automated causal discovery from limited experiments exist, but have so far rarely been tested in systems biology applications. In this work, we apply state-of-the art causal discovery methods on a large collection of public mass cytometry data sets, measuring intra-cellular signaling proteins of the human immune system and their response to several perturbations. We show how different experimental conditions can be used to facilitate causal discovery, and apply two fundamental methods that produce context-specific causal predictions. Causal predictions were reproducible across independent data sets from two different studies, but often disagree with the KEGG pathway databases. Within this context, we discuss the caveats we need to overcome for automated causal discovery to become a part of the routine data analysis in systems biology.

  18. Predicting Causal Relationships from Biological Data: Applying Automated Casual Discovery on Mass Cytometry Data of Human Immune Cells

    KAUST Repository

    Triantafillou, Sofia

    2017-03-31

    Learning the causal relationships that define a molecular system allows us to predict how the system will respond to different interventions. Distinguishing causality from mere association typically requires randomized experiments. Methods for automated causal discovery from limited experiments exist, but have so far rarely been tested in systems biology applications. In this work, we apply state-of-the art causal discovery methods on a large collection of public mass cytometry data sets, measuring intra-cellular signaling proteins of the human immune system and their response to several perturbations. We show how different experimental conditions can be used to facilitate causal discovery, and apply two fundamental methods that produce context-specific causal predictions. Causal predictions were reproducible across independent data sets from two different studies, but often disagree with the KEGG pathway databases. Within this context, we discuss the caveats we need to overcome for automated causal discovery to become a part of the routine data analysis in systems biology.

  19. Predicting Causal Relationships from Biological Data: Applying Automated Causal Discovery on Mass Cytometry Data of Human Immune Cells

    KAUST Repository

    Triantafillou, Sofia; Lagani, Vincenzo; Heinze-Deml, Christina; Schmidt, Angelika; Tegner, Jesper; Tsamardinos, Ioannis

    2017-01-01

    Learning the causal relationships that define a molecular system allows us to predict how the system will respond to different interventions. Distinguishing causality from mere association typically requires randomized experiments. Methods for automated  causal discovery from limited experiments exist, but have so far rarely been tested in systems biology applications. In this work, we apply state-of-the art causal discovery methods on a large collection of public mass cytometry data sets, measuring intra-cellular signaling proteins of the human immune system and their response to several perturbations. We show how different experimental conditions can be used to facilitate causal discovery, and apply two fundamental methods that produce context-specific causal predictions. Causal predictions were reproducible across independent data sets from two different studies, but often disagree with the KEGG pathway databases. Within this context, we discuss the caveats we need to overcome for automated causal discovery to become a part of the routine data analysis in systems biology.

  20. Predicting Causal Relationships from Biological Data: Applying Automated Causal Discovery on Mass Cytometry Data of Human Immune Cells

    KAUST Repository

    Triantafillou, Sofia

    2017-09-29

    Learning the causal relationships that define a molecular system allows us to predict how the system will respond to different interventions. Distinguishing causality from mere association typically requires randomized experiments. Methods for automated  causal discovery from limited experiments exist, but have so far rarely been tested in systems biology applications. In this work, we apply state-of-the art causal discovery methods on a large collection of public mass cytometry data sets, measuring intra-cellular signaling proteins of the human immune system and their response to several perturbations. We show how different experimental conditions can be used to facilitate causal discovery, and apply two fundamental methods that produce context-specific causal predictions. Causal predictions were reproducible across independent data sets from two different studies, but often disagree with the KEGG pathway databases. Within this context, we discuss the caveats we need to overcome for automated causal discovery to become a part of the routine data analysis in systems biology.

  1. Explaining the Development of False Memories.

    Science.gov (United States)

    Reyna, Valerie F.; Holliday, Robyn; Marche, Tammy

    2002-01-01

    Reviews explanatory dimensions of children's false memory relevant to forensic practice: measurement, development, social factors, individual differences, varieties of memories and memory judgments, and varieties of procedures inducing false memories. Asserts that recent studies fail to use techniques that separate acquiescence from memory…

  2. Emotions and false memories: valence or arousal?

    Science.gov (United States)

    Corson, Yves; Verrier, Nadège

    2007-03-01

    The effects of mood on false memories have not been studied systematically until recently. Some results seem to indicate that negative mood may reduce false recall and thus suggest an influence of emotional valence on false memory. The present research tested the effects of both valence and arousal on recall and recognition and indicates that the effect is actually due to arousal. In fact, whether participants' mood is positive, negative, or neutral, false memories are significantly more frequent under conditions of high arousal than under conditions of low arousal.

  3. Natural product derived insecticides: discovery and development of spinetoram.

    Science.gov (United States)

    Galm, Ute; Sparks, Thomas C

    2016-03-01

    This review highlights the importance of natural product research and industrial microbiology for product development in the agricultural industry, based on examples from Dow AgroSciences. It provides an overview of the discovery and development of spinetoram, a semisynthetic insecticide derived by a combination of a genetic block in a specific O-methylation of the rhamnose moiety of spinosad coupled with neural network-based QSAR and synthetic chemistry. It also emphasizes the key role that new technologies and multidisciplinary approaches play in the development of current spinetoram production strains.

  4. On the threshold of discovery

    International Nuclear Information System (INIS)

    Cherenkov, P.A.

    1986-01-01

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

  5. Remedies by competitors for false advertising.

    Science.gov (United States)

    Hirsch, B D; Wilcox, D P

    1990-05-01

    Patients who are victimized as a consequence of false medical advertising are not the only ones who can sue for damages. Under section 43(a) of the Lanham Act, effective November 17, 1989, anyone "who believes that he or she is or is likely to be damaged" by deceptive advertising may bring a civil action for damages (1). Competing physicians may sue other physicians who falsely advertise that they possess unique skills and achieve better results than other physicians because they employ exclusive methods of treatment or claim that certain surgical procedures they perform in the office are absolutely safe and without risk or who advertise false professional credentials to lure patients. Voluntary informed consent excludes the use of deceit. Misrepresentation through advertising deprives a patient of the right to exercise an informed consent (2). A patient who relies on a doctor's false advertising in agreeing to a procedure that causes the patient injury may sue for malpractice even if the procedure was performed without negligence. False medical advertising also exposes the advertiser to litigation by competitors for unfair competition. This article is concerned with the remedy that may be available for instituting private litigation against physicians and other health care providers who engage in untruthful advertising.

  6. Emerging Concepts and Methodologies in Cancer Biomarker Discovery.

    Science.gov (United States)

    Lu, Meixia; Zhang, Jinxiang; Zhang, Lanjing

    2017-01-01

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

  7. 120 YEARS SINCE THE DISCOVERY OF X-RAYS.

    Science.gov (United States)

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

    2016-09-01

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

  8. Proposal for the award of an industrial support contract for paintwork, false ceilings, plasterwork and false floors at CERN

    CERN Document Server

    2006-01-01

    This document concerns the award of a contract for paintwork, false ceilings, plasterwork and false floors at CERN. The Finance Committee is invited to agree to the negotiation of a contract with the firm PREZIOSO (FR), the lowest bidder, for the provision of paintwork, false ceilings, plasterwork and false floors at CERN for a period of three years for a total amount not exceeding 538 419 euros (830 381 Swiss francs), not subject to revision for the first two years. The contract will include options for two one-year extensions beyond the initial threeyear period.

  9. Discovery and Innovation

    African Journals Online (AJOL)

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

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

    National Research Council Canada - National Science Library

    Vaidya, Vishal S; Bonventre, Joseph V

    2010-01-01

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

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

    Science.gov (United States)

    Karimi, Mostafa

    2013-04-01

    internal climate studies in data mining and knowledge discovery techniques are used. However, it is necessary to use the KDD Approach and DM techniques in the climatic studies, specific interpreter of climate modeling result.

  12. An Evaluation of Active Learning Causal Discovery Methods for Reverse-Engineering Local Causal Pathways of Gene Regulation

    Science.gov (United States)

    Ma, Sisi; Kemmeren, Patrick; Aliferis, Constantin F.; Statnikov, Alexander

    2016-01-01

    Reverse-engineering of causal pathways that implicate diseases and vital cellular functions is a fundamental problem in biomedicine. Discovery of the local causal pathway of a target variable (that consists of its direct causes and direct effects) is essential for effective intervention and can facilitate accurate diagnosis and prognosis. Recent research has provided several active learning methods that can leverage passively observed high-throughput data to draft causal pathways and then refine the inferred relations with a limited number of experiments. The current study provides a comprehensive evaluation of the performance of active learning methods for local causal pathway discovery in real biological data. Specifically, 54 active learning methods/variants from 3 families of algorithms were applied for local causal pathways reconstruction of gene regulation for 5 transcription factors in S. cerevisiae. Four aspects of the methods’ performance were assessed, including adjacency discovery quality, edge orientation accuracy, complete pathway discovery quality, and experimental cost. The results of this study show that some methods provide significant performance benefits over others and therefore should be routinely used for local causal pathway discovery tasks. This study also demonstrates the feasibility of local causal pathway reconstruction in real biological systems with significant quality and low experimental cost. PMID:26939894

  13. Multidimensional process discovery

    NARCIS (Netherlands)

    Ribeiro, J.T.S.

    2013-01-01

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

  14. Effects of Instructions on False Recognition.

    Science.gov (United States)

    Mueller, John H.; And Others

    Four experiments were conducted to examine the effects of various processing instructions on the rate of false recognition. The continuous single-item procedure was used, and false recognitions of four types were examined: synonyms, antonyms, nonsemantic associates, and homonyms. The instructions encouraged subjects to think of associates, usages…

  15. Analytical and Experimental Performance Evaluation of BLE Neighbor Discovery Process Including Non-Idealities of Real Chipsets

    Directory of Open Access Journals (Sweden)

    David Perez-Diaz de Cerio

    2017-03-01

    Full Text Available The purpose of this paper is to evaluate from a real perspective the performance of Bluetooth Low Energy (BLE as a technology that enables fast and reliable discovery of a large number of users/devices in a short period of time. The BLE standard specifies a wide range of configurable parameter values that determine the discovery process and need to be set according to the particular application requirements. Many previous works have been addressed to investigate the discovery process through analytical and simulation models, according to the ideal specification of the standard. However, measurements show that additional scanning gaps appear in the scanning process, which reduce the discovery capabilities. These gaps have been identified in all of the analyzed devices and respond to both regular patterns and variable events associated with the decoding process. We have demonstrated that these non-idealities, which are not taken into account in other studies, have a severe impact on the discovery process performance. Extensive performance evaluation for a varying number of devices and feasible parameter combinations has been done by comparing simulations and experimental measurements. This work also includes a simple mathematical model that closely matches both the standard implementation and the different chipset peculiarities for any possible parameter value specified in the standard and for any number of simultaneous advertising devices under scanner coverage.

  16. History of the discovery of uranium fission by neutrons

    International Nuclear Information System (INIS)

    Simane, C.

    1989-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  18. Discovery learning with SAVI approach in geometry learning

    Science.gov (United States)

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

    2018-05-01

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

  19. Can False Memories Prime Problem Solutions?

    Science.gov (United States)

    Howe, Mark L.; Garner, Sarah R.; Dewhurst, Stephen A.; Ball, Linden J.

    2010-01-01

    Previous research has suggested that false memories can prime performance on related implicit and explicit memory tasks. The present research examined whether false memories can also be used to prime higher order cognitive processes, namely, insight-based problem solving. Participants were asked to solve a number of compound remote associate task…

  20. False positive rate of carbon monoxide saturation by pulse oximetry of emergency department patients.

    Science.gov (United States)

    Weaver, Lindell K; Churchill, Susan K; Deru, Kayla; Cooney, Darryl

    2013-02-01

    Symptoms of carbon monoxide (CO) poisoning are non-specific. Diagnosis requires suspicion of exposure, confirmed by measuring ambient CO levels or carboxyhemoglobin (COHb). An FDA-approved pulse oximeter (Rad-57) can measure CO saturation (S(pCO)). The device accuracy has implications for clinical decision-making. From April 1 to August 15, 2008, study personnel measured S(pCO) and documented demographic factors at time of clinical blood draw, in a convenience sample of 1,363 subjects presenting to the emergency department at Intermountain Medical Center, Murray, Utah. The technician then assayed COHb. COHb and S(pCO) values were compared by subject; false positive or negative values were defined as S(pCO) at least 3 percentage points greater or less than COHb level, reported by the manufacturer to be ± 1 SD in performance. In 1,363 subjects, 613 (45%) were male, 1,141 (84%) were light-skinned, 14 in shock, 4 with CO poisoning, and 122 (9%) met the criteria for a false positive value (range 3-19 percentage points), while 247 (18%) met the criteria for a false negative value (-13 to -3 percentage points). Risks for a false positive S(pCO) reading included being female and having a lower perfusion index. Methemoglobin, body temperature, and blood pressure also appear to influence the S(pCO) accuracy. There was variability among monitors, possibly related to technician technique, as rotation of monitors among technicians was not enforced. While the Rad-57 pulse oximeter functioned within the manufacturer's specifications, clinicians using the Rad-57 should expect some S(pCO) readings to be significantly higher or lower than COHb measurements, and should not use S(pCO) to direct triage or patient management. An elevated S(pCO) could broaden the diagnosis of CO poisoning in patients with non-specific symptoms. However, a negative S(pCO) level in patients suspected of having CO poisoning should never rule out CO poisoning, and should always be confirmed by COHb. © 2013

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