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Sample records for gx 5-1 discovery

  1. Resolving the hard X-ray emission of GX 5-1 with INTEGRAL

    DEFF Research Database (Denmark)

    Paizis, A.; Ebisawa, K.; Tikkanen, T.

    2005-01-01

    contamination from the nearby black hole candidate GRS 1758-258 above 20 keV. During our observations, GX 5-1 was mostly found in the horizontal and normal branch of its hardness intensity diagram. A clear hard X-ray emission is observed above similar to 30 keV which exceeds the exponential cut-off spectrum......We present the study of one year of INTEGRAL data on the neutron star low mass X-ray binary GX 5-1. Thanks to the excellent angular resolution and sensitivity of INTEGRAL, we are able to obtain a high quality spectrum of GX 5-1 from similar to 5keV to similar to 100 keV, for the first time without...

  2. Discovery of radio emission from the symbiotic X-ray binary system GX 1+4

    Science.gov (United States)

    van den Eijnden, J.; Degenaar, N.; Russell, T. D.; Miller-Jones, J. C. A.; Wijnands, R.; Miller, J. M.; King, A. L.; Rupen, M. P.

    2018-02-01

    We report the discovery of radio emission from the accreting X-ray pulsar and symbiotic X-ray binary GX 1+4 with the Karl G. Jansky Very Large Array. This is the first radio detection of such a system, wherein a strongly magnetized neutron star accretes from the stellar wind of an M-type giant companion. We measure a 9 GHz radio flux density of 105.3 ± 7.3 μJy, but cannot place meaningful constraints on the spectral index due to a limited frequency range. We consider several emission mechanisms that could be responsible for the observed radio source. We conclude that the observed properties are consistent with shocks in the interaction of the accretion flow with the magnetosphere, a synchrotron-emitting jet, or a propeller-driven outflow. The stellar wind from the companion is unlikely to be the origin of the radio emission. If the detected radio emission originates from a jet, it would show that strong magnetic fields (≥1012 G) do not necessarily suppress jet formation.

  3. Discovery of the near-infrared counterpart to the luminous neutron-star low-mass X-ray binary GX 3+1

    Energy Technology Data Exchange (ETDEWEB)

    Van den Berg, Maureen; Fridriksson, Joel K. [Anton Pannekoek Institute for Astronomy, University of Amsterdam, Science Park 904, 1098 XH Amsterdam (Netherlands); Homan, Jeroen [Massachusetts Institute of Technology, Kavli Institute for Astrophysics and Space Research, 70 Vassar Street, Cambridge, MA 02139 (United States); Linares, Manuel, E-mail: M.C.vandenBerg@uva.nl [Instituto de Astrofísica de Canarias (IAC), Vía Láctea s/n, La Laguna, E-38205, S/C de Tenerife (Spain)

    2014-10-01

    Using the High Resolution Camera on board the Chandra X-ray Observatory, we have measured an accurate position for the bright persistent neutron star X-ray binary and atoll source GX 3+1. At a location that is consistent with this new position, we have discovered the near-infrared (NIR) counterpart to GX 3+1 in images taken with the PANIC and FourStar cameras on the Magellan Baade Telescope. The identification of this K{sub s} = 15.8 ± 0.1 mag star as the counterpart is based on the presence of a Br γ emission line in an NIR spectrum taken with the Folded-port InfraRed Echelette spectrograph on the Baade Telescope. The absolute magnitude derived from the best available distance estimate to GX 3+1 indicates that the mass donor in the system is not a late-type giant. We find that the NIR light in GX 3+1 is likely dominated by the contribution from a heated outer accretion disk. This is similar to what has been found for the NIR flux from the brighter class of Z sources, but unlike the behavior of atolls fainter (L{sub X} ≈ 10{sup 36}-10{sup 37} erg s{sup –1}) than GX 3+1, where optically thin synchrotron emission from a jet probably dominates the NIR flux.

  4. Changing the picture of Earth's earliest fossils (3.5-1.9 Ga) with new approaches and new discoveries.

    Science.gov (United States)

    Brasier, Martin D; Antcliffe, Jonathan; Saunders, Martin; Wacey, David

    2015-04-21

    New analytical approaches and discoveries are demanding fresh thinking about the early fossil record. The 1.88-Ga Gunflint chert provides an important benchmark for the analysis of early fossil preservation. High-resolution analysis of Gunflintia shows that microtaphonomy can help to resolve long-standing paleobiological questions. Novel 3D nanoscale reconstructions of the most ancient complex fossil Eosphaera reveal features hitherto unmatched in any crown-group microbe. While Eosphaera may preserve a symbiotic consortium, a stronger conclusion is that multicellular morphospace was differently occupied in the Paleoproterozoic. The 3.46-Ga Apex chert provides a test bed for claims of biogenicity of cell-like structures. Mapping plus focused ion beam milling combined with transmission electron microscopy data demonstrate that microfossil-like taxa, including species of Archaeoscillatoriopsis and Primaevifilum, are pseudofossils formed from vermiform phyllosilicate grains during hydrothermal alteration events. The 3.43-Ga Strelley Pool Formation shows that plausible early fossil candidates are turning up in unexpected environmental settings. Our data reveal how cellular clusters of unexpectedly large coccoids and tubular sheath-like envelopes were trapped between sand grains and entombed within coatings of dripstone beach-rock silica cement. These fossils come from Earth's earliest known intertidal to supratidal shoreline deposit, accumulated under aerated but oxygen poor conditions.

  5. Changing the picture of Earth's earliest fossils (3.5-1.9 Ga) with new approaches and new discoveries

    Science.gov (United States)

    Brasier, Martin D.; Antcliffe, Jonathan; Saunders, Martin; Wacey, David

    2015-04-01

    New analytical approaches and discoveries are demanding fresh thinking about the early fossil record. The 1.88-Ga Gunflint chert provides an important benchmark for the analysis of early fossil preservation. High-resolution analysis of Gunflintia shows that microtaphonomy can help to resolve long-standing paleobiological questions. Novel 3D nanoscale reconstructions of the most ancient complex fossil Eosphaera reveal features hitherto unmatched in any crown-group microbe. While Eosphaera may preserve a symbiotic consortium, a stronger conclusion is that multicellular morphospace was differently occupied in the Paleoproterozoic. The 3.46-Ga Apex chert provides a test bed for claims of biogenicity of cell-like structures. Mapping plus focused ion beam milling combined with transmission electron microscopy data demonstrate that microfossil-like taxa, including species of Archaeoscillatoriopsis and Primaevifilum, are pseudofossils formed from vermiform phyllosilicate grains during hydrothermal alteration events. The 3.43-Ga Strelley Pool Formation shows that plausible early fossil candidates are turning up in unexpected environmental settings. Our data reveal how cellular clusters of unexpectedly large coccoids and tubular sheath-like envelopes were trapped between sand grains and entombed within coatings of dripstone beach-rock silica cement. These fossils come from Earth's earliest known intertidal to supratidal shoreline deposit, accumulated under aerated but oxygen poor conditions.

  6. The Power Spectral Properties of the Z Source GX 340+0

    NARCIS (Netherlands)

    Jonker, Peter G.; van der Klis, Michiel; Wijnands, Rudy; Homan, Jeroen; van Paradijs, Jan; Méndez, Mariano; Ford, Eric C.; Kuulkers, Erik; Lamb, Frederick K.

    2000-01-01

    We present an analysis of ~390 ks of data of the Z source GX 340+0 taken during 24 observations with the Rossi X-Ray Timing Explorer satellite. We report the discovery of a new broad component in the power spectra. The frequency of this component varied between 9 and 14 Hz and remained close to half

  7. A potential low-mass black hole in GX 339-4

    Science.gov (United States)

    Heida, Marianne; Jonker, Peter G.; Torres, Manuel; Chiavassa, Andrea

    2017-08-01

    GX 339-4 is a low mass X-ray binary (LMXB) that has been extensively studied since its discovery. All four X-ray states typically seen in X-ray binaries (XRBs) have been detected in this system, and X-ray observations of its relatively frequent outbursts have been very important in shaping the theory of LMXB outbursts. The relation between X-ray and radio emission from XRBs also relies heavily on observations of this source. However, absorption lines from the donor star in this system had never been detected because even in quiescence, the accretion disc dominates the optical spectrum. We have for the first time detected absorption lines from the donor star in near-infrared spectra of GX 339-4 obtained with X-shooter on the VLT. We confirm that the donor is a K-type subgiant and measure its radial velocity semi-amplitude to be 219 km/s, much lower than previously determined from the Bowen emission lines. This leads to a mass function of 1.91 ± 0.08 Msun, which means that GX 339-4 could harbor one of the lowest mass black holes known to date.

  8. A curious case of the accretion-powered X-ray pulsar GX 1+4

    Science.gov (United States)

    Jaisawal, Gaurava K.; Naik, Sachindra; Gupta, Shivangi; Chenevez, Jérôme; Epili, Prahlad

    2018-04-01

    We present detailed spectral and timing studies using a NuSTAR observation of GX 1+4 in October 2015 during an intermediate intensity state. The measured spin period of 176.778 s is found to be one of the highest values since its discovery. In contrast to a broad sinusoidal-like pulse profile, a peculiar sharp peak is observed in profiles below ˜25 keV. The profiles at higher energies are found to be significantly phase-shifted compared to the soft X-ray profiles. Broadband energy spectra of GX 1+4, obtained from NuSTAR and Swift observations, are described with various continuum models. Among these, a two component model consisting of a bremsstrahlung and a blackbody component is found to best-fit the phase-averaged and phase-resolved spectra. Physical models are also used to investigate the emission mechanism in the pulsar, which allows us to estimate the magnetic field strength to be in ˜(5-10)× 1012 G range. Phase-resolved spectroscopy of NuSTAR observation shows a strong blackbody emission component in a narrow pulse phase range. This component is interpreted as the origin of the peculiar peak in the pulse profiles below ≤25 keV. The size of emitting region is calculated to be ˜400 m. The bremsstrahlung component is found to dominate in hard X-rays and explains the nature of simple profiles at high energies.

  9. Investigating the Nature of GxE Interaction under Different ...

    African Journals Online (AJOL)

    for this study were from Intermediate to Late Hybrid Trials (ILHT) conducted in ... This phenomenon, referred to as COI, introduces a degree of uncertainty into the ... Investigating the Nature of GxE Interaction under Different Management Systems [3]. Materials and Methods. Setup of the trial. The number of trial sites used for ...

  10. Comparison of Two Methods for Analysis of GxE Interactions in Longitudinal Family Data: The Framingham Heart Study

    Directory of Open Access Journals (Sweden)

    Yun Ju eSung

    2014-01-01

    Full Text Available GxE interaction analysis can potentially enhance gene discovery for common complex traits. However, genome-wide interaction analysis (GWIS is computationally intensive. Moreover, analysis of longitudinal data in families is much more challenging due to the two sources of correlations arising from longitudinal measurements and family relationships. GWIS of longitudinal family data can be a computational bottleneck. Therefore, we compared two methods for analysis of longitudinal family data: a methodologically sound but computationally demanding method using the Kronecker Model (KRC and a computationally more forgiving method using the Hierarchical Linear Model (HLM. The KRC model uses a Kronecker product of an unstructured matrix for correlations among repeated measures (longitudinal and a compound symmetry matrix for correlations within families at a given visit. The HLM uses an autoregressive covariance matrix for correlations among repeated measures and a random intercept for familial correlations. We compared the two methods using the longitudinal Framingham Heart Study (FHS SHARe data. Specifically, we evaluated SNP-Alcohol (amount of alcohol consumption interaction effects on HDL-cholesterol. Keeping the prohibitive computational burden of KRC in mind, we limited the analysis to chromosome 16, where preliminary cross-sectional analysis yielded some interesting results. Our first important finding was that the HLM provided very comparable results but was remarkably faster than the KRC, making HLM the method of choice. Our second finding was that longitudinal analysis provided smaller p values, thus leading to more significant results, than cross-sectional analysis. This was particularly pronounced in identifying GxE interactions. We conclude that longitudinal analysis of GxE interactions is more powerful and that the HLM method is an optimal method of choice as compared to the computationally (prohibitively intensive KRC method.

  11. CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits

    Science.gov (United States)

    2014-01-01

    Background Genetic understanding of complex traits has developed immensely over the past decade but remains hampered by incomplete descriptions of contribution to phenotypic variance. Gene-environment (GxE) interactions are one of these contributors and in the guise of diet and physical activity are important modulators of cardiometabolic phenotypes and ensuing diseases. Results We mined the scientific literature to collect GxE interactions from 386 publications for blood lipids, glycemic traits, obesity anthropometrics, vascular measures, inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment interaction resource. We then analyzed the genes and SNPs supporting cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern characteristics of these important genetic variants. We were able to draw many observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed little overlap with variants identified by main effect GWAS, indicating the importance of environmental interactions with genetic factors on cardiometabolic traits. 2) These GxE SNPs were enriched in adaptation to climatic and geographical features, with implications on energy homeostasis and response to physical activity. 3) Comparison to gene networks responding to plasma cholesterol-lowering or regression of atherosclerotic plaques showed that GxE genes have a greater role in those responses, particularly through high-energy diets and fat intake, than do GWAS-identified genes for the same traits. Other aspects of the CardioGxE dataset were explored. Conclusions Overall, we demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit transcriptional effects or are under positive selection. Still, not all such SNPs can be assigned potential functional or regulatory roles often because data are lacking in specific cell types or from treatments that approximate the environmental factor of the GxE. With research on metabolic related

  12. XMM-Newton Observations of GX 339-4

    Science.gov (United States)

    Mushotzky, Richard F. (Technical Monitor); Miller, Jon

    2005-01-01

    Observations of GX 339-4 were completed in March, 2004, but processed data were only sent to the PI in the late fall of 2004. Thus, serious work on the observations only began in the winter and spring of 2005. Data from each of the instruments - the EPIC CCD cameras, the Reflection Grating Spectrometer, and the Optical Monitor have been reduced and a preliminary analysis is underway. Four days of simultaneous optical radio, and X-ray data was obtained at SAAO, the Australia Telescope, and RXTE, respectively, and preliminary work on the broad-band multi-wavelength lightcurves is also underway. This observational effort is the most extensive ever undertaken to observe a black hole in the "low/hard" state, and will provide new insights into accretion onto black holes at low mass accretion rates.

  13. Effects of Variable Helmet Weight on Human Response to -Gx Impact

    Science.gov (United States)

    2016-02-01

    gender difference, the female subjects were on average unable to sustain as forceful a brace during pre- impact as the males, which may account for...AFRL-RH-WP-SR-2016-0002 EFFECTS OF VARIABLE HELMET WEIGHT ON HUMAN RESPONSE TO –Gx IMPACT John R. Buhrman, Grant C. Roush, Erica M...3. DATES COVERED (From - To) Feb 2003 – Feb 2016 4. TITLE AND SUBTITLE Effects of Variable Helmet Weight on Human Response to –Gx Impact 5a

  14. Hit-to-Lead Optimization and Discovery of 5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase.

    Science.gov (United States)

    Lan, Ping; Romero, F Anthony; Wodka, Dariusz; Kassick, Andrew J; Dang, Qun; Gibson, Tony; Cashion, Daniel; Zhou, Gaochao; Chen, Yuli; Zhang, Xiaoping; Zhang, Aihua; Li, Ying; Trujillo, Maria E; Shao, Qing; Wu, Margaret; Xu, Shiyao; He, Huaibing; MacKenna, Deidre; Staunton, Jocelyn; Chapman, Kevin T; Weber, Ann; Sebhat, Iyassu K; Makara, Gergely M

    2017-11-09

    AMP-activated protein kinase (AMPK) plays an essential role as a cellular energy sensor and master regulator of metabolism in eukaryotes. Dysregulated lipid and carbohydrate metabolism resulting from insulin resistance leads to hyperglycemia, the hallmark of type 2 diabetes mellitus (T2DM). While pharmacological activation of AMPK is anticipated to improve these parameters, the discovery of selective, direct activators has proven challenging. We now describe a hit-to-lead effort resulting in the discovery of a potent and selective class of benzimidazole-based direct AMPK activators, exemplified by 5-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic acid, 42 (MK-3903). Compound 42 exhibited robust target engagement in mouse liver following oral dosing, leading to improved lipid metabolism and insulin sensitization in mice.

  15. The variable cyclotron line of GX 301-2

    Energy Technology Data Exchange (ETDEWEB)

    Kreykenbohm, I.; Wilms, J.; Coburn, W.; Kuster, M.; Rothschild, R.E.; Heindl, W.A.; Kretschmar, P.; Staubert, R

    2004-06-01

    We present a 200 ksec observation of the High Mass X-ray Binary GX 301-2 taken in 2000 November with the Rossi X-ray Timing Explorer during the pre-periastron flare and the actual periastron passage of the neutron star. To model the spectrum we use a power law with the Fermi Dirac cutoff and a cyclotron line at higher energies plus either a reflection component or a heavily absorbed partial covering component. Although completely different, both models describe the data equally well. Phase resolved spectra show that the energy and the depth of the cyclotron resonant scattering feature vary strongly with pulse phase: It is deepest in the fall of the main pulse, the rise of the secondary pulse, and the pulse minimum in-between with {tau}{sub C}{approx}0.3. In the other phase bins the line is much less deep with {tau}{sub C}{approx}0.1. The energy of the line correlates strongly with its depth and varies by 25 % from 30.1 keV in the fall of the secondary pulse to 37.9 keV in the fall of the main pulse.

  16. Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

    Science.gov (United States)

    Zhang, Li-Fan; Sun, Biao; Cao, Xin-Sheng; Liu, Chun; Yu, Zhi-Bin; Zhang, Le-Ning; Cheng, Jiu-Hua; Wu, Yan-Hong; Wu, Xing-Yu

    2003-07-01

    This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.

  17. Hard X-ray Emission along the Z Track in GX 17+ 2

    Indian Academy of Sciences (India)

    2016-01-27

    -ray Timing Experiment (HEXTE) on board Rossi X-Ray Timing Explorer for Z source GX 17+2, we investigate the evolution of its PCA spectra and HEXTE spectra along a `Z' track on its hardness-intensity diagram. A hard ...

  18. Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation

    Science.gov (United States)

    Serrador, J. M.; Wood, S. J.; Picot, P. A.; Stein, F.; Kassam, M. S.; Bondar, R. L.; Rupert, A. H.; Schlegel, T. T.

    2001-01-01

    We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P centrifugation only in the GZ group (P centrifugation. CFV decreased during HUT more significantly after centrifugation than before centrifugation in both groups (P centrifugation compared with before centrifugation, GAIN increased in both groups (P centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.

  19. New outburst of GX 339-4 detected by Faulkes Telescope South

    Science.gov (United States)

    Russell, David M.; Lewis, Fraser; Gandhi, Poshak

    2017-09-01

    We have been monitoring the black hole X-ray binary GX 339-4 with the 2-m Faulkes Telescope South (at Siding Spring, Australia) since September 2007 (e.g. ATel #1586; #1962, #2459, #2547, #3191, #4162, Cadolle Bel et al. 2011).

  20. Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation.

    Science.gov (United States)

    Serrador, J M; Wood, S J; Picot, P A; Stein, F; Kassam, M S; Bondar, R L; Rupert, A H; Schlegel, T T

    2001-11-01

    We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P e., as BP(eye) decreased), suggesting that both types of centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.

  1. Synchronization of optical links using the GOL with the TLK2501 or StratixGX buffers

    CERN Document Server

    Aslanides, Elie; Cogan, J; Dinkespiler, B; Duval, P Y; Le Gac, R; Leroy, O; Liotard, P L; Menouni, M; Tocco, L; Tsaregorodtsev, A Yu

    2004-01-01

    In this note we clarify the synchronization design for optical links when using the GOL on the emission side, the TLK2501 deserializer from Texas Instrument or a StratixGX FPGA on the reception side. We conclude with few requirements.

  2. Studies on genotype-environment interaction (GxE) in half-sib ...

    African Journals Online (AJOL)

    Studies on genotype-environment interaction (GxE) in half-sib progenies of cashew ( Anacardium occidentale L.) in Tanzania. ... The data were used to calculate the heritability and response to selection for yield, canopy diameter, trunk cross sectional area and height. The heritabilities, and hence the response, of yield were ...

  3. Optical photometry and polarimetry of GX 339-4 during its outburst rise

    NARCIS (Netherlands)

    Russell, D.M.; Lewis, F.; Casella, P.; Pretorius, M.L.; Fender, R.P.; Roche, P.; Clark, S.

    2009-01-01

    GX 339-4 is currently brightening at X-ray, UV, optical and radio frequencies (ATel #1945, #1954, #1960). Our monitoring campaign with the Faulkes Telescope South (ATel #1586) gives the following recent magnitudes (light curves are below; errors are ~ 0.02 mag): 2009-02-20 (MJD 54882.65): i' ~ 16.66

  4. Testing GxG interactions between coinfecting microbial parasite genotypes within hosts

    Directory of Open Access Journals (Sweden)

    Rebecca D Schulte

    2014-05-01

    Full Text Available Host-parasite interactions represent one of the strongest selection pressures in nature. They are often governed by genotype-specific (GxG interactions resulting in host genotypes that differ in resistance and parasite genotypes that differ in virulence depending on the antagonist’s genotype. Another type of GxG interactions, which is often neglected but which certainly influences host-parasite interactions, are those between coinfecting parasite genotypes. Mechanistically, within-host parasite interactions may range from competition for limited host resources to cooperation for more efficient host exploitation. The exact type of interaction, i.e. whether competitive or cooperative, is known to affect life-history traits such as virulence. However, the latter has been shown for chosen genotype combinations only, not considering whether the specific genotype combination per se may influence the interaction (i.e. GxG interactions. Here, we want to test for the presence of GxG interactions between coinfections of the bacterium Bacillus thuringiensis infecting the nematode Caenorhabditis elegans by combining two non-pathogenic and five pathogenic strains in all possible ways. Furthermore, we evaluate whether the type of interaction, reflected by the direction of virulence change of multiple compared to single infections, is genotype-specific. Generally, we found no indication for GxG interactions between non-pathogenic and pathogenic bacterial strains, indicating that virulence of pathogenic strains is equally affected by both non-pathogenic strains. Specific genotype combinations, however, differ in the strength of virulence change, indicating that the interaction type between coinfecting parasite strains and thus the virulence mechanism is specific for different genotype combinations. Such interactions are expected to influence host-parasite interactions and to have strong implications for coevolution.

  5. Chromospheric lines in red dwarf flare stars. I - AD Leonis and GX Andromedae

    Science.gov (United States)

    Pettersen, B. R.; Coleman, L. A.

    1981-12-01

    Line profiles with a spectral resolution of 0.45 A have been obtained for Hα(λ6563), the Na D lines (λλ5890, 5896), He I lines (λλ5876, 6678), and the Ca II infrared triplet lines (λλ8498, 8542, 8662) in the flare stars AD Leonis and GX Andromedae. The spectroscopic Reticon diode array observations of AD Leo were obtained simultaneously with high speed photometry, and major influences in the spectra due to flares are avoided by this technique. GX And has photospheric parameters very similar to AD Leo but shows a flare activity level more than one order of magnitude smaller. Simultaneous photometry was not done during spectroscopic observations of GX And because of the small probability that a flare should contaminate the data. Despite apparently equal physical parameters at the photospheric level, the chromospheric lines observed in this program appear very different in AD Leo and GX And. Hα is a prominent emission line in AD Leo with a central absorption, for which the two peaks are separated by 0.6 Å. The FWHM of the line itself is 1.35 Å in AD Leo. In contrast, the Ha line in GX And is an absorption feature with FWHM =0.75 Å. The strength of this line is too large to be formed purely in the photosphere because temperatures are so low in this region that it is transparent to Hα and consequently forms only a very weak Ha absorption line. A collisionally dominated line may strengthen its absorption feature in a chromosphere before turning into emission (Cram and Mullan), and this is probably what is seen in GX And. An emission feature in the blue wing of Hα in AD Leo, 20% above the continuum, is found to be present also in two nonflaring M dwarfs with Ha in absorption, and is associated with less TiO blanketing at that wavelength. The Na D lines are broad absorption features in both stars with equal intensity distributions in the outer wings, reflecting the similarity of photospheric conditions in these stars. In AD Leo, however, the cores of the

  6. Bounds on the degree of APN polynomials: the case of x −1 + g(x)

    DEFF Research Database (Denmark)

    Leander, Gregor; Rodier, François

    2011-01-01

    In this paper we consider APN functions $${f:\\mathcal{F}_{2^m}\\to \\mathcal{F}_{2^m}}$$ of the form f(x) = x −1 + g(x) where g is any non $${\\mathcal{F}_{2}}$$-affine polynomial. We prove a lower bound on the degree of the polynomial g. This bound in particular implies that such a function f is AP...

  7. Low-energy gamma rays from pulsar GX 1+4 balloon results

    International Nuclear Information System (INIS)

    Jayanthi, U.B.; Jablonski, F.; Braga, J.

    1987-03-01

    The results from a search of pulsed emissions in low-energy gamma rays from GX 1+4 source is presented. These pulsations, observed at gamma ray energies from an X-ray pulser, in conjuction with the period determined in X-rays, indicate a spin-down in contrast with the spin-up behavior observed by others before. (G.D.F.) [pt

  8. Spectro-Timing Study of GX 339-4 in a Hard Intermediate State

    DEFF Research Database (Denmark)

    Fürst, F.; Grinberg, V.; Tomsick, J. A.

    2016-01-01

    We present an analysis of Nuclear Spectroscopic Telescope Array observations of a hard intermediate state of the transient black hole GX 339-4 taken in 2015 January. With the source softening significantly over the course of the 1.3 day long observation we split the data into 21 sub-sets and find...... that the spectrum of all of them can be well described by a power-law continuum with an additional relativistically blurred reflection component. The photon index increases from ∼1.69 to ∼1.77 over the course of the observation. The accretion disk is truncated at around nine gravitational radii in all spectra. We...

  9. INTEGRAL and XMM-Newton spectroscopy of GX 339-4 during hard/soft intermediate and high/soft states in the 2007 outburst

    NARCIS (Netherlands)

    Caballero-García, M.D.; Miller, J.M.; Díaz Trigo, M.; Kuulkers, E.; Fabian, A.C.; Mas-Hesse, J.M.; Steeghs, D.; van der Klis, M.

    2009-01-01

    We present simultaneous XMM-Newton and International Gamma-Ray Astrophysics Laboratory (INTEGRAL) observations of the luminous black hole transient and relativistic jet source GX 339-4. GX 339-4 started an outburst on 2006 November and our observations were undertaken from 2007 January to March. We

  10. Overview of an extensive multi-wavelength study of GX 339-4 during the 2010 outburst

    NARCIS (Netherlands)

    Cadolle Bel, M.; Rodriguez, J.; D'Avanzo, P.; Russell, D.M.; Tomsick, J.; Corbel, S.; Lewis, F. W.; Rahoui, F.; Buxton, M.; Goldoni, P.; Kuulkers, E.

    2011-01-01

    Context. The microquasar GX 339−4 experienced a new outburst in 2010: it was observed simultaneously at various wavelengths from radio up to soft γ-rays. We focus on observations that are quasi-simultaneous with those made with the INTEGRAL and RXTE satellites: these were collected in 2010

  11. Analytical verification and quality assessment of the Tosoh HLC-723GX HbA1c analyzer

    Directory of Open Access Journals (Sweden)

    Marko Ris

    2017-04-01

    Full Text Available Objectives: Ion-exchange high-performance liquid chromatography (IE-HPLC has long been used as a reproducible and versatile analytical tool for HbA1c measurement.In this study, we performed analytical verification and quality assessment of the recently introduced small IE-HPLC Tosoh HLC-723GX HbA1c analyzer, and a comparison of results to immunoassay (IA and capillary electrophoresis (CE. Design and methods: The total imprecision of Tosoh HLC-723GX was verified according to CLSI EP15-A2 protocol using commercial control materials (C-QC and pooled human whole blood samples (HWB. The Sigma metric was used for the evaluation of quality targets. HbA1c results were compared to automated CE (MiniCap Flex Piercing, Sebia, France and IA (Tina-quant HbA1c Gen 2, Cobas Integra 400+, Roche Diagnostics, USA procedures. Results: The total imprecision of Tosoh HLC-723GX-HbA1c for IFCC(mmol/mol and NGSP(% units was: 1.91/1.25% (HbA1c=31 mmol/mol/5.0% and 0.51/0.63% (HbA1c=84 mmol/mol/9.8% for C-QC, and 0.39/0.2% (HbA1c=47 mmol/mol/6.5% and 0.77/0.46% (HbA1c=94 mmol/mol/10.8% in HWB samples, respectively. Bland-Altman analysis did not reveal any deviation of the results between Tosoh HLC-723GX and CE: mean difference 0.0% (95%CI: −0.02927 to 0.02653%, while the mean HbA1c difference against IA was −0.07% (95%CI: −0.1039 to −0.02765. At the selected HbA1c clinical decision level (48 mmol/mol/6,5%, six sigma analysis gave σ value of 3.91, within a desirable classification of performance. Conclusion: The analytical performance of the Tosoh HLC-723GX complies with the rigorous quality criteria for clinical use of HbA1c, with the results comparable to the CE procedure. Tosoh HLC-723GX provides a plausible analytical choice for reliable HbA1c measurement in low-volume laboratories. Keywords: HbA1c, Quality targets, Six sigma, Tosoh HLC-723GX analyzer

  12. Characteristics of centrifugally cast GX25CrNiSi18-9 steel

    Directory of Open Access Journals (Sweden)

    R. Zapała

    2011-07-01

    Full Text Available The paper presents the results of microstructural examinations of the industrial heat-resistant centrifugally cast GX25CrNiSi18-9 steel characterised by increased content of Cu. The study included changes in the microstructure of base cast steel respective of the steel held at a temperature of 900 and 950°C for 48 hours. Based on the results obtained, an increase in microhardness of the examined cast steel matrix with increasing temperature was stated, which was probably caused by fine precipitates enriched in Cr, Mo, and C forming inside the matrix grains.The layer of scale formed on the tested cast steel oxidised in the atmosphere of air at 900 and 950°C was characterised by an increased tendency to degradation with increasing temperature of the conducted tests.

  13. Broadband Spectroscopy Using Two Suzaku Observations of the HMXB GX 301-2

    Science.gov (United States)

    Suchy, Slawomir; Fuerst, Felix; Pottschmidt, Katja; Caballero, Isabel; Kreykenbohm, Ingo; Wilms, Joern; Markowitz, Alex; Rothschild, Richard E.

    2012-01-01

    We present the analysis of two Suzaku observations of GX 301-2 at two orbital phases after the periastron passage. Variations in the column density of the line-of-sight absorber are observed, consistent with accretion from a clumpy wind. In addition to a CRSF, multiple fluorescence emission lines were detected in both observations. The variations in the pulse profiles and the CRSF throughout the pulse phase have a signature of a magnetic dipole field. Using a simple dipole model we calculated the expected magnetic field values for different pulse phases and were able to extract a set of geometrical angles, loosely constraining the dipole geometry in the neutron star. From the variation of the CRSF width and energy, we found a geometrical solution for the dipole, making the inclination consistent with previously published values.

  14. 34 CFR 5.1 - Act.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Act. 5.1 Section 5.1 Education Office of the Secretary...-10) Definitions § 5.1 Act. As used in this part, Act means section 552 of title 5, United States Code, as amended by Pub. L. 90-23, codifying the Act of July 4, 1966, sometimes referred to as the “Freedom...

  15. 36 CFR 5.1 - Advertisements.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Advertisements. 5.1 Section 5... AND PRIVATE OPERATIONS § 5.1 Advertisements. Commercial notices or advertisements shall not be... or advertisement is of goods, services, or facilities available within the park area and such notices...

  16. 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....

  17. GxGrare: gene-gene interaction analysis method for rare variants from high-throughput sequencing data.

    Science.gov (United States)

    Kwon, Minseok; Leem, Sangseob; Yoon, Joon; Park, Taesung

    2018-03-19

    With the rapid advancement of array-based genotyping techniques, genome-wide association studies (GWAS) have successfully identified common genetic variants associated with common complex diseases. However, it has been shown that only a small proportion of the genetic etiology of complex diseases could be explained by the genetic factors identified from GWAS. This missing heritability could possibly be explained by gene-gene interaction (epistasis) and rare variants. There has been an exponential growth of gene-gene interaction analysis for common variants in terms of methodological developments and practical applications. Also, the recent advancement of high-throughput sequencing technologies makes it possible to conduct rare variant analysis. However, little progress has been made in gene-gene interaction analysis for rare variants. Here, we propose GxGrare which is a new gene-gene interaction method for the rare variants in the framework of the multifactor dimensionality reduction (MDR) analysis. The proposed method consists of three steps; 1) collapsing the rare variants, 2) MDR analysis for the collapsed rare variants, and 3) detect top candidate interaction pairs. GxGrare can be used for the detection of not only gene-gene interactions, but also interactions within a single gene. The proposed method is illustrated with 1080 whole exome sequencing data of the Korean population in order to identify causal gene-gene interaction for rare variants for type 2 diabetes. The proposed GxGrare performs well for gene-gene interaction detection with collapsing of rare variants. GxGrare is available at http://bibs.snu.ac.kr/software/gxgrare which contains simulation data and documentation. Supported operating systems include Linux and OS X.

  18. INTEGRAL hard X-ray detection of HMXB GX 304-1 and H1417-624

    DEFF Research Database (Denmark)

    Manousakis, A.; Beckmann, V.; Bianchin, V.

    2008-01-01

    We report on the first detection of the Be star HMXBs GX 304-1 and H1417-624 above 20 keV with the IBIS/ISGRI X-ray imager on board INTEGRAL. From 2008-06-24 to 2008-07-09, INTEGRAL performed monitoring observations of the Galactic plane around l=305 degrees for a total exposure time of 352 ksec....

  19. Fuzzy Λ gX r -sets and generalization of closed sets in generalized fuzzy topological spaces

    Directory of Open Access Journals (Sweden)

    Jayasree Chakraborty

    2017-06-01

    Full Text Available The aim of this paper is to introduce fuzzy ΛgXr-set and to study some of its generalized forms. The structure constituted by fuzzy Λ g X r -set is also included in the treatise. Moreover we define generalized fuzzy gX -closed set and fuzzy Λ g X r -closed set, which are the weaker forms of fuzzy gX -closed set. The above two weaker forms are independent to each other but jointly they imply fuzzy gX -closed set. Finally, in addition, as the application of fuzzy Λ g X r -closed set, we study fuzzy (Λ , g X r Y g - continuity and fuzzy (Λ , gf g X r X Y  g g -continuity and a few of their properties. In general, fuzzy contra ( , X Y g g -continuity does not imply fuzzy ( , X Y g g -continuity, but this paper provides one condition under which the fact is true.

  20. Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.

    Directory of Open Access Journals (Sweden)

    Lin Lei

    Full Text Available Coronaviruses are a family of large positive-sense RNA viruses that are responsible for a wide range of important veterinary and human diseases. Nsp1 has been shown to have an important role in the pathogenetic mechanisms of coronaviruses in vivo. To assess the function of a relatively conserved domain (LLRKxGxKG of MHV nsp1, a mutant virus, MHV-nsp1-27D, with a 27 nts (LLRKxGxKG deletion in nsp1, was constructed using a reverse genetic system with a vaccinia virus vector. The mutant virus had similar growth kinetics to MHV-A59 wild-type virus in 17CI-1 cells, but was highly attenuated in vivo. Moreover, the mutant virus completely protected C57BL/6 mice from a lethal MHV-A59 challenge. To further analyze the mechanism of the attenuation of the mutant virus, changes in reporter gene expression were measured in nsp1- or nsp1-27D-expressing cells; the results showed that nsp1 inhibited reporter gene expression controlled by different promoters, but that this inhibition was reduced for nsp1-27D. The research in vivo and in vitro suggests that the LLRKxGxKG region of nsp1 may play an important role in this process.

  1. Beyond Discovery

    DEFF Research Database (Denmark)

    Korsgaard, Steffen; Sassmannshausen, Sean Patrick

    2017-01-01

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

  2. 12 CFR 5.1 - Scope.

    Science.gov (United States)

    2010-01-01

    ... COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY RULES, POLICIES, AND PROCEDURES FOR CORPORATE ACTIVITIES § 5.1 Scope. This part establishes rules, policies and procedures of the Office of the Comptroller of the Currency (OCC) for corporate activities and transactions involving national banks. It contains...

  3. Evolution of the reverberation lag in GX 339-4 at the end of an outburst

    Science.gov (United States)

    De Marco, B.; Ponti, G.; Petrucci, P. O.; Clavel, M.; Corbel, S.; Belmont, R.; Chakravorty, S.; Coriat, M.; Drappeau, S.; Ferreira, J.; Henri, G.; Malzac, J.; Rodriguez, J.; Tomsick, J. A.; Ursini, F.; Zdziarski, A. A.

    2017-10-01

    We studied X-ray reverberation lags in the Black hole X-ray binary (BHXRB) GX 339-4 at the end of the 2014-2015 outburst. We analysed data from an XMM-Newton campaign covering the end of the transition from the soft to hard state, and the decrease of luminosity in the hard state. During all the observations we detected, at high frequencies, significant disc variability, responding to variations of the power-law emission with an average time delay of ∼0.009 ± 0.002 s. These new detections of disc thermal reverberation add to those previously obtained and suggest the lag to be always present in hard and hard-intermediate states. Our study reveals a net decrease of lag amplitude as a function of luminosity. We ascribe this trend to variations of the inner flow geometry. A possible scenario implies a decrease of the inner disc truncation radius as the luminosity increases at the beginning of the outburst, followed by an increase of the inner disc truncation radius as the luminosity decreases at the end of the outburst. Finally, we found hints of FeK reverberation (∼3σ significance) during the best quality observation of the XMM monitoring. The lag at the FeK energy has similar amplitude as that of the thermally reprocessed component, as expected if the same irradiated region of the disc is responsible for producing both the thermalized and reflected components. This finding suggests FeK reverberation in BHXRBs to be at the reach of current detectors provided observations of sufficiently long exposure are available.

  4. Genome sequencing of a virulent avian Pasteurella multocida strain GX-Pm reveals the candidate genes involved in the pathogenesis.

    Science.gov (United States)

    Yu, Chengjie; Sizhu, Suolang; Luo, Qingping; Xu, Xuewen; Fu, Lei; Zhang, Anding

    2016-04-01

    Pasteurella multocida (P. multocida) was first shown to be the causative agent of fowl cholera by Louis Pasteur in 1881. First genomic study was performed on an avirulent avian strain Pm70, and until 2013, two genomes of virulent avian strains X73 and P1059 were sequenced. Comparative genome study supplied important information for further study on the pathogenesis of fowl cholera. In the previous study, a capsular serotype A strain GX-Pm was isolated from the liver of a chicken, which died during an outbreak of fowl cholera in 2011. The strain showed multiple drug resistance and was highly virulent to chickens. Therefore, the present study performed the genome sequencing and a comparative genomic analysis to reveal the candidate genes involved in virulence of P. multocida. Sequenced draft genome sequence of GX-Pm was 2,292,886 bp, contained 2941 protein-coding genes, 5 genomic islands, 4 IS elements and 2 prophage regions. Notability, all the predicted drug-resistance genes were included in predicted genomic islands. A comparative genome study on virulent avian strains P1059, X73 and GX-Pm with the avirulent avian strain Pm 70 indicated that 475 unique genes were only identified in either of virulent strains but absent in the avirulent strain. Among these genes, 20 genes were contained within genomes of all three virulent strains, including a few of putative virulence genes. Further characterization of the pathogenic functions of these genes would benefit the understanding of pathogenesis of fowl cholera. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. NuSTARand Swift observations of the very high state in GX 339-4: Weighing the black hole with X-rays

    DEFF Research Database (Denmark)

    Parker, M. L.; Tomsick, J. A.; Kennea, J. A.

    2016-01-01

    We present results from spectral fitting of the very high state of GX 339-4 with Nuclear Spectroscopic Telescope Array (NuSTAR) and Swift. We use relativistic reflection modeling to measure the spin of the black hole and inclination of the inner disk and find a spin of a = 0.95(-0.08)(+0.02) and ......We present results from spectral fitting of the very high state of GX 339-4 with Nuclear Spectroscopic Telescope Array (NuSTAR) and Swift. We use relativistic reflection modeling to measure the spin of the black hole and inclination of the inner disk and find a spin of a = 0...

  6. The evolution of the timing properties of the black-hole transient GX 339-4 during its 2002/2003 outburst

    NARCIS (Netherlands)

    Belloni, T.; Homan, J.; Casella, P.; van der Klis, M.; Nespoli, E.; Lewin, W.H.G.; Miller, J.M.; Méndez, R.M.

    2005-01-01

    We present the results of the timing and color analysis of more than two hundred RXTE/PCA observations of the bright black-hole transient GX 339-4 obtained during its 2002/2003 outburst. The color-intensity evolution of the system, coupled to the properties of its fast time variability, allow the

  7. The evolution of the X-ray phase lags during the outbursts of the black hole candidate GX 339-4

    NARCIS (Netherlands)

    Altamirano, Diego; Méndez, Mariano

    2015-01-01

    Owing to the frequency and reproducibility of its outbursts, the black hole candidate GX 339-4 has become the standard against which the outbursts of other black hole candidate are matched up. Here we present the first systematic study of the evolution of the X-ray lags of the broad-band variability

  8. Evidence of Black Hole Spin in GX 339-4: XMM-Newton/EPIC-pn and RXTE Spectroscopy of the Very High State

    NARCIS (Netherlands)

    Miller, J.M.; Fabian, A.C.; Reynolds, C.S.; Nowak, M.A.; Homan, J.; Freyberg, M.J.; Ehle, M.; Belloni, T.; Wijnands, R.A.D.; van der Klis, M.; Charles, P.A.; Lewin, W.H.G.

    2004-01-01

    We have analyzed spectra of the Galactic black hole GX 339-4 obtained through simultaneous 76 ks XMM-Newton/EPIC-pn and 10 ks Rossi X-Ray Timing Explorer observations during a bright phase of its 2002-2003 outburst. An extremely skewed, relativistic Fe Kalpha emission line and ionized disk

  9. Peak Luminosities of the Hard States of GX 339-4: Implications for the Accretion Geometry, Disk Mass, and Black Hole Mass

    NARCIS (Netherlands)

    Yu, W.; Lamb, F.K.; Fender, R.; van der Klis, M.

    2007-01-01

    We have analyzed observations of the black hole transient GX 339-4 made with the Rossi X-ray Timing Explorer (RXTE) and the Burst and Transient Source Experiment (BATSE) on board the Compton Gamma-Ray Observatory (CGRO). We have found a nearly linear relation between the peak flux during the

  10. Data Discovery

    Directory of Open Access Journals (Sweden)

    Gerhard Weikum

    2013-07-01

    Full Text Available Discovery of documents, data sources, facts, and opinions is at the very heart of digital information and knowledge services. Being able to search, discover, compile, and analyse relevant information for a user’s specific tasks is of utmost importance in science (e.g., computational life sciences, digital humanities, etc., business (e.g., market and media analytics, customer relationship management, etc. , and society at large (e.g., consumer information, traffic logistics, health discussions, etc..

  11. Cosmic Discovery

    Science.gov (United States)

    Harwit, Martin

    1984-04-01

    In the remarkable opening section of this book, a well-known Cornell astronomer gives precise thumbnail histories of the 43 basic cosmic discoveries - stars, planets, novae, pulsars, comets, gamma-ray bursts, and the like - that form the core of our knowledge of the universe. Many of them, he points out, were made accidentally and outside the mainstream of astronomical research and funding. This observation leads him to speculate on how many more major phenomena there might be and how they might be most effectively sought out in afield now dominated by large instruments and complex investigative modes and observational conditions. The book also examines discovery in terms of its political, financial, and sociological context - the role of new technologies and of industry and the military in revealing new knowledge; and methods of funding, of peer review, and of allotting time on our largest telescopes. It concludes with specific recommendations for organizing astronomy in ways that will best lead to the discovery of the many - at least sixty - phenomena that Harwit estimates are still waiting to be found.

  12. The fungi: 1, 2, 3 ... 5.1 million species?

    Science.gov (United States)

    Blackwell, Meredith

    2011-03-01

    Fungi are major decomposers in certain ecosystems and essential associates of many organisms. They provide enzymes and drugs and serve as experimental organisms. In 1991, a landmark paper estimated that there are 1.5 million fungi on the Earth. Because only 70000 fungi had been described at that time, the estimate has been the impetus to search for previously unknown fungi. Fungal habitats include soil, water, and organisms that may harbor large numbers of understudied fungi, estimated to outnumber plants by at least 6 to 1. More recent estimates based on high-throughput sequencing methods suggest that as many as 5.1 million fungal species exist. Technological advances make it possible to apply molecular methods to develop a stable classification and to discover and identify fungal taxa. Molecular methods have dramatically increased our knowledge of Fungi in less than 20 years, revealing a monophyletic kingdom and increased diversity among early-diverging lineages. Mycologists are making significant advances in species discovery, but many fungi remain to be discovered. Fungi are essential to the survival of many groups of organisms with which they form associations. They also attract attention as predators of invertebrate animals, pathogens of potatoes and rice and humans and bats, killers of frogs and crayfish, producers of secondary metabolites to lower cholesterol, and subjects of prize-winning research. Molecular tools in use and under development can be used to discover the world's unknown fungi in less than 1000 years predicted at current new species acquisition rates.

  13. Temperature-dependent thermal and thermoelectric properties of n -type and p -type S c1 -xM gxN

    Science.gov (United States)

    Saha, Bivas; Perez-Taborda, Jaime Andres; Bahk, Je-Hyeong; Koh, Yee Rui; Shakouri, Ali; Martin-Gonzalez, Marisol; Sands, Timothy D.

    2018-02-01

    Scandium Nitride (ScN) is an emerging rocksalt semiconductor with octahedral coordination and an indirect bandgap. ScN has attracted significant attention in recent years for its potential thermoelectric applications, as a component material in epitaxial metal/semiconductor superlattices, and as a substrate for defect-free GaN growth. Sputter-deposited ScN thin films are highly degenerate n -type semiconductors and exhibit a large thermoelectric power factor of ˜3.5 ×10-3W /m -K2 at 600-800 K. Since practical thermoelectric devices require both n- and p-type materials with high thermoelectric figures-of-merit, development and demonstration of highly efficient p-type ScN is extremely important. Recently, the authors have demonstrated p-type S c1 -xM gxN thin film alloys with low M gxNy mole-fractions within the ScN matrix. In this article, we demonstrate temperature dependent thermal and thermoelectric transport properties, including large thermoelectric power factors in both n- and p-type S c1 -xM gxN thin film alloys at high temperatures (up to 850 K). Employing a combination of temperature-dependent Seebeck coefficient, electrical conductivity, and thermal conductivity measurements, as well as detailed Boltzmann transport-based modeling analyses of the transport properties, we demonstrate that p-type S c1 -xM gxN thin film alloys exhibit a maximum thermoelectric power factor of ˜0.8 ×10-3W /m -K2 at 850 K. The thermoelectric properties are tunable by adjusting the M gxNy mole-fraction inside the ScN matrix, thereby shifting the Fermi energy in the alloy films from inside the conduction band in case of undoped n -type ScN to inside the valence band in highly hole-doped p -type S c1 -xM gxN thin film alloys. The thermal conductivities of both the n- and p-type films were found to be undesirably large for thermoelectric applications. Thus, future work should address strategies to reduce the thermal conductivity of S c1 -xM gxN thin-film alloys, without affecting

  14. THE HOST GALAXY OF THE SUPER-LUMINOUS SN 2010gx AND LIMITS ON EXPLOSIVE {sup 56}Ni PRODUCTION

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ting-Wan; Smartt, Stephen J.; Kotak, Rubina; McCrum, Matt; Fraser, Morgan [Astrophysics Research Centre, School of Mathematics and Physics, Queen' s University Belfast, Belfast BT7 1NN (United Kingdom); Bresolin, Fabio; Kudritzki, Rolf-Peter [Institute for Astronomy, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Pastorello, Andrea [INAF-Osservatorio Astronomico di Padova, vicolo dell' Osservatorio 5, I-35122 Padova (Italy); Valenti, Stefano [Las Cumbres Observatory Global Telescope Network, Inc., Santa Barbara, CA 93117 (United States)

    2013-02-01

    Super-luminous supernovae have a tendency to occur in faint host galaxies which are likely to have low mass and low metallicity. While these extremely luminous explosions have been observed from z = 0.1 to 1.55, the closest explosions allow more detailed investigations of their host galaxies. We present a detailed analysis of the host galaxy of SN 2010gx (z = 0.23), one of the best studied super-luminous type Ic supernovae. The host is a dwarf galaxy (M{sub g} = -17.42 {+-} 0.17) with a high specific star formation rate. It has a remarkably low metallicity of 12 + log (O/H) = 7.5 {+-} 0.1 dex as determined from the detection of the [O III] {lambda}4363 line. This is the first reliable metallicity determination of a super-luminous stripped-envelope supernova host. We collected deep multi-epoch imaging with Gemini + GMOS between 240 and 560 days after explosion to search for any sign of radioactive {sup 56}Ni, which might provide further insights on the explosion mechanism and the progenitor's nature. We reach griz magnitudes of m{sub AB} {approx} 26, but do not detect SN 2010gx at these epochs. The limit implies that any {sup 56}Ni production was similar to or below that of SN 1998bw (a luminous type Ic SN that produced around 0.4 M{sub Sun} of {sup 56}Ni). The low volumetric rates of these supernovae ({approx}10{sup -4} of the core-collapse population) could be qualitatively matched if the explosion mechanism requires a combination of low-metallicity (below 0.2 Z{sub Sun }), high progenitor mass (>60 M{sub Sun }) and high rotation rate (fastest 10% of rotators).

  15. THE HOST GALAXY OF THE SUPER-LUMINOUS SN 2010gx AND LIMITS ON EXPLOSIVE 56Ni PRODUCTION

    International Nuclear Information System (INIS)

    Chen, Ting-Wan; Smartt, Stephen J.; Kotak, Rubina; McCrum, Matt; Fraser, Morgan; Bresolin, Fabio; Kudritzki, Rolf-Peter; Pastorello, Andrea; Valenti, Stefano

    2013-01-01

    Super-luminous supernovae have a tendency to occur in faint host galaxies which are likely to have low mass and low metallicity. While these extremely luminous explosions have been observed from z = 0.1 to 1.55, the closest explosions allow more detailed investigations of their host galaxies. We present a detailed analysis of the host galaxy of SN 2010gx (z = 0.23), one of the best studied super-luminous type Ic supernovae. The host is a dwarf galaxy (M g = –17.42 ± 0.17) with a high specific star formation rate. It has a remarkably low metallicity of 12 + log (O/H) = 7.5 ± 0.1 dex as determined from the detection of the [O III] λ4363 line. This is the first reliable metallicity determination of a super-luminous stripped-envelope supernova host. We collected deep multi-epoch imaging with Gemini + GMOS between 240 and 560 days after explosion to search for any sign of radioactive 56 Ni, which might provide further insights on the explosion mechanism and the progenitor's nature. We reach griz magnitudes of m AB ∼ 26, but do not detect SN 2010gx at these epochs. The limit implies that any 56 Ni production was similar to or below that of SN 1998bw (a luminous type Ic SN that produced around 0.4 M ☉ of 56 Ni). The low volumetric rates of these supernovae (∼10 –4 of the core-collapse population) could be qualitatively matched if the explosion mechanism requires a combination of low-metallicity (below 0.2 Z ☉ ), high progenitor mass (>60 M ☉ ) and high rotation rate (fastest 10% of rotators).

  16. Discovery Mondays

    CERN Multimedia

    2003-01-01

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

  17. The evolution of the X-ray phase lags during the outbursts of the black hole candidate GX 339-4

    Science.gov (United States)

    Altamirano, Diego; Méndez, Mariano

    2015-06-01

    Owing to the frequency and reproducibility of its outbursts, the black hole candidate GX 339-4 has become the standard against which the outbursts of other black hole candidate are matched up. Here we present the first systematic study of the evolution of the X-ray lags of the broad-band variability component (0.008-5 Hz) in GX 339-4 as a function of the position of the source in the hardness-intensity diagram. The hard photons always lag the soft ones, consistent with previous results. In the low-hard state the lags correlate with X-ray intensity, and as the source starts the transition to the intermediate/soft states, the lags first increase faster, and then appear to reach a maximum, although the exact evolution depends on the outburst and the energy band used to calculate the lags. The time of the maximum of the lags appears to coincide with a sudden drop of the optical/near-infrared flux, the fractional rms amplitude of the broad-band component in the power spectrum, and the appearance of a thermal component in the X-ray spectra, strongly suggesting that the lags can be very useful to understand the physical changes that GX 339-4 undergoes during an outburst. We find strong evidence for a connection between the evolution of the cut-off energy of the hard component in the energy spectrum and the phase lags, suggesting that the average magnitude of the lags is correlated with the properties of the corona/jet rather than those of the disc. Finally, we show that the lags in GX 339-4 evolve in a similar manner to those of the black hole candidate Cygnus X-1, suggesting similar phenomena could be observable in other black hole systems.

  18. Does accounting for gene-environment (GxE) interaction increase the power to detect the effect of a gene in a multifactorial disease?

    Science.gov (United States)

    Selinger-Leneman, Hana; Genin, Emmanuelle; Norris, Jill M; Khlat, Myriam

    2003-04-01

    Despite tremendous efforts, few genes involved in the susceptibility for complex disorders have been identified. One explanation is that these disorders are a result of an interaction between genes and environment, and under such conditions, it may be difficult to measure the true genetic effect without accounting for the interaction. Umbach and Weinberg ([2000] Am. J. Hum. Genet. 66:251-261) proposed an association test which looks at the joint effects of genotype and environment, using case-parent trios. In this study, we explore under which conditions accounting for GxE interaction enhances one's ability to detect the role of genetic factors in complex diseases. Using asymptotic power calculations, we investigate the power to detect the gene effect over varying exposure frequencies and different scenarios of GxE interaction. We show that for a given sample size, interaction scenario, and allele frequency, the actual gain in power while accounting for the interaction depends on the magnitude of the exposure frequency: the largest gains are seen for relatively low exposure frequencies. Moreover, a loss of power can be observed when the exposure is frequent and/or the exposure effect is strong. If we consider a gene with a disease allele frequency of 0.2, with no effect in the absence of exposure, an exposure with a 10-fold increase risk and a GxE relative risk of 2, then when the exposure frequency is 0.1, accounting for GxE interaction increases the power to detect the gene effect in 200 trios by 10%; alternatively, when the exposure frequency is 0.9, it decreases the power by 15%. Copyright 2003 Wiley-Liss, Inc.

  19. CARAT-GxG: CUDA-Accelerated Regression Analysis Toolkit for Large-Scale Gene-Gene Interaction with GPU Computing System.

    Science.gov (United States)

    Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung

    2014-01-01

    In genome-wide association studies (GWAS), regression analysis has been most commonly used to establish an association between a phenotype and genetic variants, such as single nucleotide polymorphism (SNP). However, most applications of regression analysis have been restricted to the investigation of single marker because of the large computational burden. Thus, there have been limited applications of regression analysis to multiple SNPs, including gene-gene interaction (GGI) in large-scale GWAS data. In order to overcome this limitation, we propose CARAT-GxG, a GPU computing system-oriented toolkit, for performing regression analysis with GGI using CUDA (compute unified device architecture). Compared to other methods, CARAT-GxG achieved almost 700-fold execution speed and delivered highly reliable results through our GPU-specific optimization techniques. In addition, it was possible to achieve almost-linear speed acceleration with the application of a GPU computing system, which is implemented by the TORQUE Resource Manager. We expect that CARAT-GxG will enable large-scale regression analysis with GGI for GWAS data.

  20. 39 CFR 5.1 - Establishment and appointment.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Establishment and appointment. 5.1 Section 5.1 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE COMMITTEES (ARTICLE V) § 5.1 Establishment and appointment. From time to time the Board may establish by resolution...

  1. NuSTAR and XMM-Newton Observations of the 2015 Outburst Decay of GX 339-4

    Energy Technology Data Exchange (ETDEWEB)

    Stiele, H.; Kong, A. K. H., E-mail: hstiele@mx.nthu.edu.tw [National Tsing Hua University, Department of Physics and Institute of Astronomy, No. 101 Sect. 2 Kuang-Fu Road, 30013, Hsinchu, Taiwan (China)

    2017-07-20

    The extent of the accretion disk in the low/hard state of stellar mass black hole X-ray binaries remains an open question. There is some evidence suggesting that the inner accretion disk is truncated and replaced by a hot flow, while the detection of relativistic broadened iron emission lines seems to require an accretion disk extending fully to the innermost stable circular orbit. We present comprehensive spectral and timing analyses of six Nuclear Spectroscopic Telescope Array and XMM-Newton observations of GX 339–4 taken during outburst decay in the autumn of 2015. Using a spectral model consisting of a thermal accretion disk, Comptonized emission, and a relativistic reflection component, we obtain a decreasing photon index, consistent with an X-ray binary during outburst decay. Although we observe a discrepancy in the inner radius of the accretion disk and that of the reflector, which can be attributed to the different underlying assumptions in each model, both model components indicate a truncated accretion disk that resiles with decreasing luminosity. The evolution of the characteristic frequency in Fourier power spectra and their missing energy dependence support the interpretation of a truncated and evolving disk in the hard state. The XMM-Newton data set allowed us to study, for the first time, the evolution of the covariance spectra and ratio during outburst decay. The covariance ratio increases and steeps during outburst decay, consistent with increased disk instabilities.

  2. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis

    Science.gov (United States)

    Nguyen, Mai; Marcellus, Richard C.; Roulston, Anne; Watson, Mark; Serfass, Lucile; Murthy Madiraju, S. R.; Goulet, Daniel; Viallet, Jean; Bélec, Laurent; Billot, Xavier; Acoca, Stephane; Purisima, Enrico; Wiegmans, Adrian; Cluse, Leonie; Johnstone, Ricky W.; Beauparlant, Pierre; Shore, Gordon C.

    2007-01-01

    Elevated expression of members of the BCL-2 pro-survival family of proteins can confer resistance to apoptosis in cancer cells. Small molecule obatoclax (GX15-070), which is predicted to occupy a hydrophobic pocket within the BH3 binding groove of BCL-2, antagonizes these members and induces apoptosis, dependent on BAX and BAK. Reconstitution in yeast confirmed that obatoclax acts on the pathway and overcomes BCL-2-, BCL-XL-, BCL-w-, and MCL-1-mediated resistance to BAX or BAK. The compound potently interfered with the direct interaction between MCL-1 and BAK in intact mitochondrial outer membrane and inhibited the association between MCL-1 and BAK in intact cells. MCL-1 has been shown to confer resistance to the BCL-2/BCL-XL/BCL-w-selective antagonist ABT-737 and to the proteasome inhibitor bortezomib. In both cases, this resistance was overcome by obatoclax. These findings support a rational clinical development opportunity for the compound in cancer indications or treatments where MCL-1 contributes to resistance to cell killing. PMID:18040043

  3. NuSTAR and XMM-Newton Observations of the 2015 Outburst Decay of GX 339-4

    Science.gov (United States)

    Stiele, H.; Kong, A. K. H.

    2017-07-01

    The extent of the accretion disk in the low/hard state of stellar mass black hole X-ray binaries remains an open question. There is some evidence suggesting that the inner accretion disk is truncated and replaced by a hot flow, while the detection of relativistic broadened iron emission lines seems to require an accretion disk extending fully to the innermost stable circular orbit. We present comprehensive spectral and timing analyses of six Nuclear Spectroscopic Telescope Array and XMM-Newton observations of GX 339-4 taken during outburst decay in the autumn of 2015. Using a spectral model consisting of a thermal accretion disk, Comptonized emission, and a relativistic reflection component, we obtain a decreasing photon index, consistent with an X-ray binary during outburst decay. Although we observe a discrepancy in the inner radius of the accretion disk and that of the reflector, which can be attributed to the different underlying assumptions in each model, both model components indicate a truncated accretion disk that resiles with decreasing luminosity. The evolution of the characteristic frequency in Fourier power spectra and their missing energy dependence support the interpretation of a truncated and evolving disk in the hard state. The XMM-Newton data set allowed us to study, for the first time, the evolution of the covariance spectra and ratio during outburst decay. The covariance ratio increases and steeps during outburst decay, consistent with increased disk instabilities.

  4. Study of the Many Fluorescent Lines and the Absorption Variability in GX 301-2 with XMM-Newton

    Science.gov (United States)

    Fuerst, F.; Suchy, S.; Kreykenbohm, I.; Barragan, L.; Wilms, J.; Pottschmidt, K.; Caballero, I.; Kretschmar, P.; Ferrigno, C.; Rothschild, R. E.

    2011-01-01

    We present an in-depth study of the High Mass X-ray Binary (HMXB) GX 301-2 during its pre-periastron flare using data from the XMM-Newton satellite. The energy spectrum shows a power law continuum absorbed by a large equivalent hydrogen column on the order of 10(exp 24)/ sq cm and a prominent Fe K-alpha fluorescent emission line. Besides the Fe K-alpha line, evidence for Fe K-Beta, Ni K-alpha, Ni K-Beta, S K-alpha, Ar K-alpha, Ca K-alpha, and Cr K-alpha fluorescent lines is found. The observed line strengths are consistent with fluorescence in a cold absorber. This is the first time that Cr K-alpha is seen in emission in the X-ray spectrum of a HMXB. In addition to the modulation by the strong pulse period of approx 685 sec the source is highly variable and shows different states of activity. We perform time-resolved as well as pulse-to-pulse resolved spectroscopy to investigate differences between these states of activity. We find that fluorescent line fluxes are strongly variable and generally follow the overall flux. The N-H value is variable by a factor of 2, but not correlated to continuum normalization. We find an interval of low flux in the light curve in which the pulsations cease almost completely, without any indication of an increasing absorption column. We investigate this dip in detail and argue that it is most likely that during the dip the accretion ceased and the afterglow of the fluorescent iron accounted for the main portion of the X-ray flux. A similar dip was found earlier in RXTE data, and we compare our findings to these results.

  5. The evolution of the disc variability along the hard state of the black hole transient GX 339-4

    Science.gov (United States)

    De Marco, B.; Ponti, G.; Muñoz-Darias, T.; Nandra, K.

    2015-12-01

    We report on the analysis of hard-state power spectral density function (PSD) of GX 339-4 down to the soft X-ray band, where the disc significantly contributes to the total emission. At any luminosity probed, the disc in the hard state is intrinsically more variable than in the soft state. However, the fast decrease of disc variability as a function of luminosity, combined with the increase of disc intensity, causes a net drop of fractional variability at high luminosities and low energies, which reminds the well-known behaviour of disc-dominated energy bands in the soft state. The peak frequency of the high-frequency Lorentzian (likely corresponding to the high-frequency break seen in active galactic nuclei, AGN) scales with luminosity, but we do not find evidence for a linear scaling. In addition, we observe that this characteristic frequency is energy dependent. We find that the normalization of the PSD at the peak of the high-frequency Lorentzian decreases with luminosity at all energies, though in the soft band this trend is steeper. Together with the frequency shift, this yields quasi-constant high-frequency (5-20 Hz) fractional rms at high energies, with less than 10 per cent scatter. This reinforces previous claims suggesting that the high-frequency PSD solely scales with black hole mass. On the other hand, this constancy breaks down in the soft band (where the scatter increases to ˜30 per cent). This is a consequence of the additional contribution from the disc component, and resembles the behaviour of optical variability in AGN.

  6. Secondary Metabolites of a Mangrove Endophytic Fungus Aspergillus terreus (No. GX7-3B from the South China Sea

    Directory of Open Access Journals (Sweden)

    Yong-Cheng Lin

    2013-07-01

    Full Text Available The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1, together with anhydrojavanicin (2, 8-O-methylbostrycoidin (3, 8-O-methyljavanicin (4, botryosphaerone D (5, 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6, 3β,5α-dihydroxy-(22E,24R-ergosta-7,22-dien-6-one (7, 3β,5α,14α-trihydroxy-(22E,24R-ergosta-7, 22-dien-6-one (8, NGA0187 (9 and beauvericin (10, were isolated. Their structures were elucidated by analysis of spectroscopic data. This is the first report of a natural origin for compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine microorganism for the first time. In the bioactive assays in vitro, compounds 2, 3, 9 and 10 displayed remarkable inhibiting actions against α-acetylcholinesterase (AChE with IC50 values 2.01, 6.71, 1.89, and 3.09 μM, respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10 exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and KB cell lines with IC50 values 4.98 and 2.02 (MCF-7, 1.95 and 0.82 (A549, 0.68 and 1.14 (Hela, and 1.50 and 1.10 μM (KB, respectively; compound 8 had weak inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6 and 9 exhibited no inhibitory activities against them.

  7. The evolution of the timing properties of the black-hole transient GX 339-4 during its 2002/2003 outburst

    OpenAIRE

    Belloni, T.; Homan, J.; Casella, P.; van der Klis, M.; Nespoli, E.; Lewin, W.H.G.; Miller, J.M.; Méndez, R.M.

    2005-01-01

    We present the results of the timing and color analysis of more than two hundred RXTE/PCA observations of the bright black-hole transient GX 339-4 obtained during its 2002/2003 outburst. The color-intensity evolution of the system, coupled to the properties of its fast time variability, allow the identification of four separate states. Depending on the state, strong noise is detected, together with a variety of quasi-periodic oscillations at frequencies from 0.2 to 8 Hz. We present a characte...

  8. Mechanics and composition of middle cerebral arteries from simulated microgravity rats with and without 1-h/d -Gx gravitation.

    Directory of Open Access Journals (Sweden)

    Jiu-Hua Cheng

    Full Text Available BACKGROUND: To elucidate further from the biomechanical aspect whether microgravity-induced cerebral vascular mal-adaptation might be a contributing factor to postflight orthostatic intolerance and the underlying mechanism accounting for the potential effectiveness of intermittent artificial gravity (IAG in preventing this adverse effect. METHODOLOGY/PRINCIPAL FINDINGS: Middle cerebral arteries (MCAs were isolated from 28-day SUS (tail-suspended, head-down tilt rats to simulate microgravity effect, S+D (SUS plus 1-h/d -Gx gravitation by normal standing to simulate IAG, and CON (control rats. Vascular myogenic reactivity and circumferential stress-strain and axial force-pressure relationships and overall stiffness were examined using pressure arteriography and calculated. Acellular matrix components were quantified by electron microscopy. The results demonstrate that myogenic reactivity is susceptible to previous pressure-induced, serial constrictions. During the first-run of pressure increments, active MCAs from SUS rats can strongly stiffen their wall and maintain the vessels at very low strains, which can be prevented by the simulated IAG countermeasure. The strains are 0.03 and 0.14 respectively for SUS and S+D, while circumferential stress being kept at 0.5 (106 dyn/cm2. During the second-run pressure steps, both the myogenic reactivity and active stiffness of the three groups declined. The distensibility of passive MCAs from S+D is significantly higher than CON and SUS, which may help to attenuate the vasodilatation impairment at low levels of pressure. Collagen and elastin percentages were increased and decreased, respectively, in MCAs from SUS and S+D as compared with CON; however, elastin was higher in S+D than SUS rats. CONCLUSIONS: Susceptibility to previous myogenic constrictions seems to be a self-limiting protective mechanism in cerebral small resistance arteries to prevent undue cerebral vasoconstriction during orthostasis at 1-G

  9. NuSTAR AND Swift Observations of the Very High State in GX 339-4: Weighing the Black Hole With X-Rays

    Science.gov (United States)

    Parker, M. L.; Tomsick, J. A.; Kennea, J. A.; Miller, J. M.; Harrison, F. A.; Barret, D.; Boggs, S. E.; Christensen, F. E.; Craig, W. W.; Fabian, A. C.; hide

    2016-01-01

    We present results from spectral fitting of the very high state of GX339-4 with Nuclear Spectroscopic Telescope Array (NuSTAR) and Swift. We use relativistic reflection modeling to measure the spin of the black hole and inclination of the inner disk and find a spin of a = 0.95+0.08/-0.02 and inclination of 30deg +/- 1deg (statistical errors). These values agree well with previous results from reflection modeling. With the exceptional sensitivity of NuSTAR at the high-energy side of the disk spectrum, we are able to constrain multiple physical parameters simultaneously using continuum fitting. By using the constraints from reflection as input for the continuum fitting method, we invert the conventional fitting procedure to estimate the mass and distance of GX 339-4 using just the X-ray spectrum, finding a mass of 9.0+1.6/-1.2 Stellar Mass and distance of 8.4 +/- 0.9 kpc (statistical errors).

  10. 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 ...

  11. Plantics-GX: a biodegradable and cost-effective thermoset plastic that is 100% plant-based

    NARCIS (Netherlands)

    Alberts, A.H.; Rothenberg, G.

    2017-01-01

    We recount here the story of the discovery and invention of a family of thermoset resins that are fully biodegradable and plant-based. The resin is prepared by polymerising glycerol, the simplest trialcohol, with citric acid, the simplest abundantly available triacid. Mixing these two chemicals at

  12. 26 CFR 400.5-1 - Redemption by United States.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Redemption by United States. 400.5-1 Section... by United States. (a) Scope. The purpose of this section is to prescribe rules with respect to the provisions contained in section 7425(d), relating to redemption of real property by the United States...

  13. Chandra/High Energy Transmission Grating Spectrometer Spectroscopy of the Galactic Black Hole GX 339-4: A Relativistic Iron Emission Line and Evidence for a Seyfert-like Warm Absorber

    NARCIS (Netherlands)

    Miller, J.M.; Raymond, J.; Fabian, A.C.; Homan, J.; Nowak, M.A.; Wijnands, R.A.D.; van der Klis, M.; Belloni, T.; Tomsick, J.A.; Smith, D.M.; Charles, P.A.; Lewin, W.H.G.

    2004-01-01

    We observed the Galactic black hole GX 339-4 with the Chandra High Energy Transmission Grating Spectrometer (HETGS) for 75 ks during the decline of its 2002-2003 outburst. The sensitivity of this observation provides an unprecedented glimpse of a Galactic black hole at about a tenth of the

  14. Relativistic Iron Emission Lines and Multi-Wavelength Variability in a Low L_X State of the Black Hole GX 339-4: A Prominent Role for Jets?

    NARCIS (Netherlands)

    Miller, J.M.; Homan, J.; Steeghs, D.; Rupen, M.; Wijnands, R.A.D.; Charles, P.

    2004-01-01

    We observed the Galactic black hole GX 339-4 in its ``low/hard" state continuously for nearly 4 days in X-rays, radio, and optical/IR bands using XMM-Newton (and, RXTE), the Australia Telescope, and the South African Astronomical Observatory. Strong, regular, and remarkably similar variability is

  15. A Comparison of the Variability of the Symbiotic X-ray Binaries GX 1+4, 4U 1954+31, and 4U 1700+24 from Swift/BAT and RXTE/ASM Observations

    Science.gov (United States)

    Corbet, R. H. D.; Sokoloski, J. L.; Mukai, K.; Markwardt, C. B.; Tueller, J.

    2007-01-01

    We present an analysis of the X-ray variability of three symbiotic X-ray binaries, GX 1+4, 4U 1700+24, and 4U 1954+31, using observations made with the Swift Burst Alert Telescope (BAT) and the Rossi X-ray Timing Explorer (RXTE) All-Sky Monitor (ASM). Observations of 4U 1954+31 with the Swift BAT show modulation at a period near 5 hours. Models to explain this modulation are discussed including the presence of an exceptionally slow X-ray pulsar in the system and accretion instabilities. We conclude that the most likely interpretation is that 4U 1954+31 contains one of the slowest known X-ray pulsars. Unlike 4U 1954+31, neither GX 1+4 nor 4U 1700+24 show any evidence for modulation on a timescale of hours. An analysis of the RXTE ASM light curves of GX l+4, 4U 1700+24, and 4U 1954+31 does not show the presence of periodic modulation in any source, although there is considerable variability on long timescales for all three sources. There is no modulation in GX 1+4 on either the optical 1161 day orbital period or a previously reported 304 day X-ray period. For 4U 1700+24 we do not confirm the 404 day period previously proposed for this source from a shorter duration ASM light curve.

  16. 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 and organi......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...... their performance....

  17. New Criticality Safety Analysis Capabilities in SCALE 5.1

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Stephen M [ORNL; DeHart, Mark D [ORNL; Dunn, Michael E [ORNL; Goluoglu, Sedat [ORNL; Horwedel, James E [ORNL; Petrie Jr, Lester M [ORNL; Rearden, Bradley T [ORNL; Williams, Mark L [ORNL

    2007-01-01

    Version 5.1 of the SCALE computer software system developed at Oak Ridge National Laboratory, released in 2006, contains several significant enhancements for nuclear criticality safety analysis. This paper highlights new capabilities in SCALE 5.1, including improved resonance self-shielding capabilities; ENDF/B-VI.7 cross-section and covariance data libraries; HTML output for KENO V.a; analytical calculations of KENO-VI volumes with GeeWiz/KENO3D; new CENTRMST/PMCST modules for processing ENDF/B-VI data in TSUNAMI; SCALE Generalized Geometry Package in NEWT; KENO Monte Carlo depletion in TRITON; and plotting of cross-section and covariance data in Javapeno.

  18. GEMPAK 5.1 - A GENERAL METEOROLOGICAL PACKAGE (UNIX VERSION)

    Science.gov (United States)

    Desjardins, M. L.

    1994-01-01

    GEMPAK is a general meteorological software package developed at NASA/Goddard Space Flight Center. It includes programs to analyze and display surface, upper-air, and gridded data, including model output. There are very general programs to list, edit, and plot data on maps, to display profiles and time series, to draw and fill contours, to draw streamlines, to plot symbols for clouds, sky cover, and pressure tendency, and draw cross sections in the case of gridded data and sounding data. In addition, there are Barnes objective analysis programs to grid surface and upper-air data. The programs include the capabilities to derive meteorological parameters from those found in the dataset, to perform vertical interpolations of sounding data to different coordinate systems, and to compute an extensive set of gridded diagnostic quantities by specifying various nested combinations of scalars and vector arithmetic, algebraic, and differential operators. The GEMPAK 5.1 graphics/transformation subsystem, GEMPLT, provides device-independent graphics. GEMPLT also has the capability to display output in a variety of map projections or overlaid on satellite imagery. GEMPAK 5.1 is written in FORTRAN 77 and C-language and has been implemented on VAX computers under VMS and on computers running the UNIX operating system. During installation and normal use, this package occupies approximately 100Mb of hard disk space. The UNIX version of GEMPAK includes drivers for several graphic output systems including MIT's X Window System (X11,R4), Sun GKS, PostScript (color and monochrome), Silicon Graphics, and others. The VMS version of GEMPAK also includes drivers for several graphic output systems including PostScript (color and monochrome). The VMS version is delivered with the object code for the Transportable Applications Environment (TAE) program, version 4.1 which serves as a user interface. A color monitor is recommended for displaying maps on video display devices. Data for rendering

  19. 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

  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. "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…

  2. VMware vSphere 5.1 cookbook

    CERN Document Server

    GB, Abhilash

    2013-01-01

    A fast-paced, task-oriented Cookbook covering recipes on the installation and configuration of vSphere 5.1 components. The recipes are accompanied with relevant screenshots with an intention to provide a visual guidance as well. The book concentrates more on the actual task rather than the theory around it, making it easier to understand what is really needed to achieve the task.This book is a guide for anyone who wants to learn how to install and configure VMware vSphere components. This is an excellent handbook for support professionals or for anyone intending to give themselves a head start

  3. The geomagnetic anomalies before Dengta M5.1 earthquake

    Science.gov (United States)

    Jia, L.; Qiao, Z.; Zhang, G.

    2017-12-01

    Using the geomagnetic data from January 2008 to December 2015 that observed by four geomagnetic stations in china such as Tieling, Yingkou, Tonghua and Zhaoyang, we researched Dengta M5.1 earthquake through medium-term earthquake forecast methods such as geomagnetic harmonic wave amplitude ratio(HWAR) and spatial correlation of geomagnetic field F value (SC-F). And by scanning a large area of geomagnetic low-point displacement (LPD) based on geomagnetic Z component data provided by 16 stations around the epicenter, we analyzed short-term earthquake geomagnetic anomalies that may occur before the earthquake. Then we summarized the different magnetic medium to short-term anomaly characteristics that appeared before the earthquake. The study showed that the HWAR method appeared some decline anomalies in 2-4years before Dengta M5.1 earthquake and the earthquake occurred in the rising stage; some obvious decline anomalies appeared before earthquake in the SC-F result, and a clear dividing line appeared when13 days before earthquake occurred in the LPD method.

  4. 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.

  5. Fateful discovery almost forgotten

    CERN Multimedia

    1989-01-01

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

  6. 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)

  7. The Evolution of GX 339-4 in the Low-hard State as Seen by NuSTAR and Swift

    Science.gov (United States)

    Wang-Ji, Jingyi; García, Javier A.; Steiner, James F.; Tomsick, John A.; Harrison, Fiona A.; Bambi, Cosimo; Petrucci, Pierre-Olivier; Ferreira, Jonathan; Chakravorty, Susmita; Clavel, Maïca

    2018-03-01

    We analyze 11 Nuclear Spectroscopic Telescope Array and Swift observations of the black hole X-ray binary GX 339–4 in the hard state, 6 of which were taken during the end of the 2015 outburst and 5 during a failed outburst in 2013. These observations cover luminosities from 0.5% to 5% of the Eddington luminosity. Implementing the most recent version of the reflection model relxillCp, we perform simultaneous spectral fits on both data sets to track the evolution of the properties in the accretion disk, including the inner edge radius, the ionization, and the temperature of the thermal emission. We also constrain the photon index and electron temperature of the primary source (the “corona”). We observe a maximum truncation radius of 37 R g in the preferred fit for the 2013 data set, and a marginal correlation between the level of truncation and luminosity. We also explore a self-consistent model under the framework of coronal Comptonization, and find consistent results regarding the disk truncation in the 2015 data, providing a more physical preferred fit for the 2013 observations.

  8. Influence of heat treatment on microstructure and properties of GX12CrMoVNbN9-1 cast steel

    Directory of Open Access Journals (Sweden)

    G. Golański

    2010-07-01

    Full Text Available The paper presents results of research on the influence of multistage heat treatment on microstructure and properties of high-chromiummartensitic GX12CrMoVNbN9 – 1 (GP91 steel. The material under investigation were samples taken out from a test coupon. Heattreatment of GP91 cast steel was performed at the parameters of temperature and time typical of treatment for multi-ton steel casts. The research has proved that in the as-received condition (as-cast state GP91 cast steel was characterized by a coarse grain, martensitic microstructure which provided the required standard mechanical properties. The heat treatment of GP91 cast steel contributed to obtainment of a fine grain microstructure of high tempered martensite with numerous precipitations of carbides of diverse size. The GP91 cast steel structure received through heat treatment made it possible to obtain high plastic properties, particularly impact strength, maintaining strength properties on the level of the required minimum.

  9. Several tetratricopeptide repeat (TPR) motifs of FANCG are required for assembly of the BRCA2/D1-D2-G-X3 complex, FANCD2 monoubiquitylation and phleomycin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, James B. [Molecular Oncology and Stem Cell Research Group, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB (United Kingdom); Blom, Eric [Department of Clinical Genetics and Human Genetics, VU University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Cunningham, Ryan; Xiao, Yuxuan [Molecular Oncology and Stem Cell Research Group, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB (United Kingdom); Kupfer, Gary M. [Departments of Pediatrics and Pathology, Yale University School of Medicine, Section of Hematology/Oncology, 333 Cedar Street, New Haven, CT 0652 (United States); Jones, Nigel J., E-mail: njjones@liv.ac.uk [Molecular Oncology and Stem Cell Research Group, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB (United Kingdom)

    2010-07-07

    The Fanconi anaemia (FA) FANCG protein is an integral component of the FA nuclear core complex that is required for monoubiquitylation of FANCD2. FANCG is also part of another protein complex termed D1-D2-G-X3 that contains FANCD2 and the homologous recombination repair proteins BRCA2 (FANCD1) and XRCC3. Formation of the D1-D2-G-X3 complex is mediated by serine-7 phosphorylation of FANCG and occurs independently of the FA core complex and FANCD2 monoubiquitylation. FANCG contains seven tetratricopeptide repeat (TPR) motifs that mediate protein-protein interactions and here we show that mutation of several of the TPR motifs at a conserved consensus residue ablates the in vivo binding activity of FANCG. Expression of mutated TPR1, TPR2, TPR5 and TPR6 in Chinese hamster fancg mutant NM3 fails to functionally complement its hypersensitivities to mitomycin C (MMC) and phleomycin and fails to restore FANCD2 monoubiquitylation. Using co-immunoprecipitation analysis, we demonstrate that these TPR-mutated FANCG proteins fail to interact with BRCA2, XRCC3, FANCA or FANCF. The interactions of other proteins in the D1-D2-G-X3 complex are also absent, including the interaction of BRCA2 with both the monoubiquitylated (FANCD2-L) and non-ubiquitylated (FANCD2-S) isoforms of FANCD2. Interestingly, a mutation of TPR7 (R563E), that complements the MMC and phleomycin hypersensitivity of human FA-G EUFA316 cells, fails to complement NM3, despite the mutated FANCG protein co-precipitating with FANCA, BRCA2 and XRCC3. Whilst interaction of TPR7-mutated FANCG with FANCF does appear to be reduced in NM3, FANCD2 is monoubiquitylated suggesting that sub-optimal interactions of FANCG in the core complex and the D1-D2-G-X3 complex are responsible for the observed MMC- and phleomycin-hypersensitivity, rather than a defect in FANCD2 monoubiquitylation. Our data demonstrate that FANCG functions as a mediator of protein-protein interactions and is vital for the assembly of multi-protein complexes

  10. Discovery of Fullerenes

    Indian Academy of Sciences (India)

    ... Journal of Science Education; Volume 2; Issue 1. Discovery of Fullerenes Giving a New Shape to Carbon Chemistry. Rathna Ananthaiah. Research News Volume 2 Issue 1 January 1997 pp 68-73. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/01/0068-0073 ...

  11. Landmark Discoveries in Neurosciences

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 11. Landmark Discoveries in Neurosciences. Niranjan Kambi Neeraj Jain. General Article Volume 17 Issue 11 November 2012 pp 1054-1064. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. The discovery of fission

    International Nuclear Information System (INIS)

    McKay, H.A.C.

    1978-01-01

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

  13. 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

  14. Discovery of charm

    Energy Technology Data Exchange (ETDEWEB)

    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/sup 0/,D/sup +/ 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.

  15. Atlas of Astronomical Discoveries

    CERN Document Server

    Schilling, Govert

    2011-01-01

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

  16. Characterization of the Infrared/X-ray sub-second variability for the black-hole transient GX 339-4

    Science.gov (United States)

    Vincentelli, F. M.; Casella, P.; Maccarone, T. J.; Uttley, P.; Gandhi, P.; Belloni, T.; De Marco, B.; Russell, D. M.; Stella, L.; O'Brien, K.

    2018-03-01

    We present a detailed analysis of the X-ray/IR fast variability of the Black-Hole Transient GX 339-4 during its low/hard state in August 2008. Thanks to simultaneous high time-resolution observations made with the VLT and RXTE, we performed the first characterisation of the sub-second variability in the near-infrared band - and of its correlation with the X-rays - for a low-mass X-ray binary, using both time- and frequency-domain techniques. We found a power-law correlation between the X-ray and infrared fluxes when measured on timescales of 16 seconds, with a marginally variable slope, steeper than the one found on timescales of days at similar flux levels. We suggest the variable slope - if confirmed - could be due to the infrared flux being a non-constant combination of both optically thin and optically thick synchrotron emission from the jet, as a result of a variable self-absorption break. From cross spectral analysis we found an approximately constant infrared time lag of ≈0.1s, and a very high coherence of ˜90 per cent on timescales of tens of seconds, slowly decreasing toward higher frequencies. Finally, we report on the first detection of a linear rms-flux relation in the emission from a low-mass X-ray binary jet, on timescales where little correlation is found between the X-rays and the jet emission itself. This suggests that either the inflow variations and jet IR emission are coupled by a non-linear or time-variable transform, or that the IR rms-flux relation is not transferred from the inflow to the jet, but is an intrinsic property of emission processes in the jet.

  17. The Evolution of the Phase Lags Associated with the Type-C Quasi-periodic Oscillation in GX 339–4 during the 2006/2007 Outburst

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang; Chen, Li [Department of Astronomy, Beijing Normal University, Beijing 100875 (China); Wang, Yanan; Méndez, Mariano [Kapteyn Astronomical Institute, University of Groningen, P.O. Box 800, NL-9700 AV Groningen (Netherlands); Qu, Jinlu [Key Laboratory for Particle Astrophysics, Institute of High Energy Physics, CAS, Beijing 100049 (China); Altamirano, Diego [Department of Physics and Astronomy, University of Southampton, Southampton, Hampshire SO17 1BJ (United Kingdom); Belloni, Tomaso, E-mail: 201431160006@mail.bnu.edu.cn [INAF-Osservatorio Astronomico di Brera, via E. Bianchi 46, I-23807 Merate (Italy)

    2017-08-20

    We present the evolution of the phase lags associated with the type-C QPO in GX 339–4 during the rising phase of the 2006/2007 outburst. We find that the phase lags at the QPO frequency are always positive (hard) and show very different behavior between QPOs with frequencies below and above ∼1.7 Hz: when the QPO frequency is below ∼1.7 Hz, the phase lags increase both with QPO frequency and energy, while when the QPO frequency is above ∼1.7 Hz, the phase lags remain more or less constant. When the QPO frequency is higher than ∼1.7 Hz, a broad feature is always present in the lag–energy spectra at around 6.5 keV, suggesting that the reflection component may have a significant contribution to the phase lags. Below ∼1.7 Hz, the QPO rms first decreases with energy and then turns to almost flat, while above ∼1.7 Hz, the QPO rms increases with energy. During the transition from the low-hard state to the hard-intermediate state, the second harmonic and subharmonic of this QPO appear in the power density spectra. The second-harmonic and subharmonic phase lags show very similar evolutions for their centroid frequencies. However, the energy dependence of the second-harmonic and subharmonic phase lags are quite different. Our results suggest that, at different phases of the outburst, different mechanisms may be responsible for the phase lags of the QPO. We briefly discuss the possible scenarios for producing the lags.

  18. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

    also contributed to the discovery of new isotopes. More recently, most of the very neutron- rich isotopes have been discovered by projectile fission. After a brief summary of the discovery of fission process itself, these production mechanisms will be discussed. The paper concludes with an outlook on future discoveries of ...

  19. Recent Discoveries and Bible Translation.

    Science.gov (United States)

    Harrelson, Walter

    1990-01-01

    Discusses recent discoveries for "Bible" translation with a focus on the "Dead Sea Scrolls." Examines recent discoveries that provide direct support for alternative reading of biblical passages and those discoveries that have contributed additional insight to knowledge of cultural practices, especially legal and religious…

  20. Fateful discovery almost forgotten

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

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

  1. 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.

  2. Discovery of TUG-770

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Hansen, Steffen Vissing Fahnøe; Urban, Christian

    2013-01-01

    Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical...... and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing....

  3. Discovery concepts for Mars

    Science.gov (United States)

    Luhmann, J. G.; Russell, C. T.; Brace, L. H.; Nagy, A. F.; Jakosky, B. M.; Barth, C. A.; Waite, J. H.

    1992-01-01

    Two focused Mars missions that would fit within the guidelines for the proposed Discovery line are discussed. The first mission would deal with the issue of the escape of the atmosphere (Mars') to space. A complete understanding of this topic is crucial to deciphering the evolution of the atmosphere, climate change, and volatile inventories. The second mission concerns the investigation of remanent magnetization of the crust and its relationship to the ionosphere and the atmosphere.

  4. Physical, biochemical and genetic characterization of enterocin CE5-1 produced by Enterococcus faecium CE5-1 isolated from Thai indigenous chicken intestinal tract

    Directory of Open Access Journals (Sweden)

    Kraiyot Saelim

    2015-06-01

    Full Text Available Enterocin CE5-1 produced by Enterococcus faecium CE5-1 isolated from the chicken gastrointestinal tract was active in the wide range of pH 2-10 and temperature 30-100°C and sensitive to proteolytic enzymes and -amylase. It remained active after storage at -20°C for 2 months. Moreover, enterocin CE5-1 showed antibacterial activity against lactobacilli, bacilli, listeria, staphylococci and enterococci, especially antibiotic-resistant enterococci. In vitro study of enterocin CE5-1 decreased the population of Ent. faecalis VanB from 6.03 to 4.03 log CFU/ml. The lethal mode of action of enterocin CE5-1 appeared to be pore and filament formation in the cell wall. PCR sequencing analysis revealed the presence of two open reading frames (ORFs, containing enterocin CE5-1 (entCE5-1 and enterocin immunity (entI gene. Therefore, enterocin CE5-1 from Ent. faecium CE5-1 could possibly be used as an antimicrobial agent to control foodborne pathogen, spoilage bacteria and antibiotic-resistant enterococci in foods, feeds and the environments.

  5. Automated Supernova Discovery (Abstract)

    Science.gov (United States)

    Post, R. S.

    2015-12-01

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

  6. 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

  7. Optogenetics enlightens neuroscience drug discovery.

    Science.gov (United States)

    Song, Chenchen; Knöpfel, Thomas

    2016-02-01

    Optogenetics - the use of light and genetics to manipulate and monitor the activities of defined cell populations - has already had a transformative impact on basic neuroscience research. Now, the conceptual and methodological advances associated with optogenetic approaches are providing fresh momentum to neuroscience drug discovery, particularly in areas that are stalled on the concept of 'fixing the brain chemistry'. Optogenetics is beginning to translate and transit into drug discovery in several key domains, including target discovery, high-throughput screening and novel therapeutic approaches to disease states. Here, we discuss the exciting potential of optogenetic technologies to transform neuroscience drug discovery.

  8. Discovery of neptunium

    International Nuclear Information System (INIS)

    Abelson, P.H.

    1990-01-01

    A number of distinguished scientists irradiated uranium with neutrons during 1934-1938. All were knowledgeable about the periodic table. They observed a number of beta-emitting activities that seemed to be from transuranic elements. They assumed that elements 93 and 94 would have chemical properties similar to rhenium and osmium respectively. In consequence discovery of fission and neptunium was delayed. After fission was finally demonstrated, a new search for element 93 was initiated by McMillan. He showed that when thin films of uranium are exposed to neutrons, high energy fission products leave the film - 23 minute and 2.3 day activities. The 23 minute activity was known to be an isotope of uranium. Chemistry performed by Abelson in May 1940 produced conclusive evidence that the 2.3 day activity was from the transuranic element 93 later named neptunium

  9. Hippocampus discovery First steps

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

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

  10. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

    2015-08-28

    Aug 28, 2015 ... Of the about 3000 isotopes presently known, about 20% have been discovered in fission. The history of fission as it relates to the discovery of isotopes as well as the various reaction mechanisms leading to isotope discoveries involving fission are presented.

  11. Discovery Mondays: Surveyors' Tools

    CERN Multimedia

    2003-01-01

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

  12. Analiza igre branilcev v conski obrambi 5:1 pri rokometu

    OpenAIRE

    Kozole, Rok

    2017-01-01

    V diplomski nalogi je predstavljena analiza igre branilcev v conski obrambi 5:1 pri rokometu. Obrambna formacija 5:1 je po obrambi 6:0 druga najpogosteje uporabljena obrambna formacija, katere se poslužujejo tako ekipe iz vrhunskega rokometa kot tudi ekipe, ki tekmujejo v ligah nižje kakovosti. V skladu s hitrim razvojem rokometne igre se je razvijala tudi obramba 5:1. Obrambna formacija 5:1 se pri mlajših rokometaših uporablja tudi kot prehodna obramba oz. temelj za prehod iz bolj globokih (...

  13. Supernovae Discovery Efficiency

    Science.gov (United States)

    John, Colin

    2018-01-01

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

  14. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi

    2014-01-01

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

  15. Discovery of the cadmium isotopes

    International Nuclear Information System (INIS)

    Amos, S.; Thoennessen, M.

    2010-01-01

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

  16. 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

  17. Scientific discovery through weighted sampling

    NARCIS (Netherlands)

    E. Sidirourgos (Eleftherios); M.L. Kersten (Martin); P.A. Boncz (Peter)

    2013-01-01

    textabstractScientific discovery has shifted from being an exercise of theory and computation, to become the exploration of an ocean of observational data. Scientists explore data originated from modern scientific instruments in order to discover

  18. Exosomes in urine biomarker discovery.

    Science.gov (United States)

    Huebner, Alyssa R; Somparn, Poorichaya; Benjachat, Thitima; Leelahavanichkul, Asada; Avihingsanon, Yingyos; Fenton, Robert A; Pisitkun, Trairak

    2015-01-01

    Nanovesicles present in urine the so-called urinary exosomes have been found to be secreted by every epithelial cell type lining the urinary tract system in human. Urinary exosomes are an appealing source for biomarker discovery as they contain molecular constituents of their cell of origin, including proteins and genetic materials, and they can be isolated in a non-invasive manner. Following the discovery of urinary exosomes in 2004, many studies have been performed using urinary exosomes as a starting material to identify biomarkers in various renal, urogenital, and systemic diseases. Here, we describe the discovery of urinary exosomes and address the issues on the collection, isolation, and normalization of urinary exosomes as well as delineate the systems biology approach to biomarker discovery using urinary exosomes.

  19. 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.)

  20. 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.

  1. Universal Knowledge Discovery from Big Data: Towards a Paradigm Shift from 'Knowledge Discovery' to 'Wisdom Discovery'

    OpenAIRE

    Shen, Bin

    2014-01-01

    Many people hold a vision that big data will provide big insights and have a big impact in the future, and big-data-assisted scientific discovery is seen as an emerging and promising scientific paradigm. However, how to turn big data into deep insights with tremendous value still remains obscure. To meet the challenge, universal knowledge discovery from big data (UKD) is proposed. The new concept focuses on discovering universal knowledge, which exists in the statistical analyses of big data ...

  2. 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.

  3. CMAQv5.1 Base NEIv1 AQS hourly site compare files

    Data.gov (United States)

    U.S. Environmental Protection Agency — CMAQv5.1 Base NEIv1 AQS hourly sitex files containing hourly paired model/ob data for the AQS network. This dataset is associated with the following publication:...

  4. CMAQv5.1 with new dust IMPROVE site compare files

    Data.gov (United States)

    U.S. Environmental Protection Agency — CMAQv5.1 with a new dust module IMPROVE sitex files containing 24-hr (every 3rd day) paired model/ob data for the IMPROVE network. This dataset is associated with...

  5. CMAQv5.1 with new dust AQS Hourly site compare files

    Data.gov (United States)

    U.S. Environmental Protection Agency — CMAQv5.1 with a new dust module AQS Hourly sitex files containing hourly paired model/ob data for the AQS network. This dataset is associated with the following...

  6. Label-free drug discovery

    Directory of Open Access Journals (Sweden)

    Ye eFang

    2014-03-01

    Full Text Available Current drug discovery is dominated by label-dependent molecular approaches, which screen drugs in the context of a predefined and target-based hypothesis in vitro. Given that target-based discovery has not transformed the industry, phenotypic screen that identifies drugs based on a specific phenotype of cells, tissues, or animals has gained renewed interest. However, owing to the intrinsic complexity in drug-target interactions, there is often a significant gap between the phenotype screened and the ultimate molecular mechanism of action sought. This paper presents a label-free strategy for early drug discovery. This strategy combines label-free cell phenotypic profiling with computational approaches, and holds promise to bridge the gap by offering a kinetic and holistic representation of the functional consequences of drugs in disease relevant cells that is amenable to mechanistic deconvolution.

  7. 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.

  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. In defence of discovery learning.

    Science.gov (United States)

    Vereijken, B; Whiting, H T

    1990-06-01

    The present paper discusses the influence of different training methods--i.e., knowledge of results, preferred frequency, and the availability of a model--on the learning of a complex motor skill, in this case the learning of slalom ski-type movements on a ski-simulator. Results of three experiments performed on this apparatus showed that, although the training methods used influence the course of learning, none of the methods used was actually superior to discovery learning. It is suggested that discovery learning forces the learner to explore the dynamics of the system in which he or she operates, in an iterative way. Possibilities for cooperative working between prescription and discovery learning are discussed.

  10. Advancements in Aptamer Discovery Technologies.

    Science.gov (United States)

    Gotrik, Michael R; Feagin, Trevor A; Csordas, Andrew T; Nakamoto, Margaret A; Soh, H Tom

    2016-09-20

    Affinity reagents that specifically bind to their target molecules are invaluable tools in nearly every field of modern biomedicine. Nucleic acid-based aptamers offer many advantages in this domain, because they are chemically synthesized, stable, and economical. Despite these compelling features, aptamers are currently not widely used in comparison to antibodies. This is primarily because conventional aptamer-discovery techniques such as SELEX are time-consuming and labor-intensive and often fail to produce aptamers with comparable binding performance to antibodies. This Account describes a body of work from our laboratory in developing advanced methods for consistently producing high-performance aptamers with higher efficiency, fewer resources, and, most importantly, a greater probability of success. We describe our efforts in systematically transforming each major step of the aptamer discovery process: selection, analysis, and characterization. To improve selection, we have developed microfluidic devices (M-SELEX) that enable discovery of high-affinity aptamers after a minimal number of selection rounds by precisely controlling the target concentration and washing stringency. In terms of improving aptamer pool analysis, our group was the first to use high-throughput sequencing (HTS) for the discovery of new aptamers. We showed that tracking the enrichment trajectory of individual aptamer sequences enables the identification of high-performing aptamers without requiring full convergence of the selected aptamer pool. HTS is now widely used for aptamer discovery, and open-source software has become available to facilitate analysis. To improve binding characterization, we used HTS data to design custom aptamer arrays to measure the affinity and specificity of up to ∼10(4) DNA aptamers in parallel as a means to rapidly discover high-quality aptamers. Most recently, our efforts have culminated in the invention of the "particle display" (PD) screening system, which

  11. Conceptos de ataque frente a variantes defensivas 6:0 y 5:1 [Concepts of attacks against the variants defensive 6:0 and 5:1

    Directory of Open Access Journals (Sweden)

    Juan de Dios Román Seco

    2009-12-01

    Full Text Available Resumen: La filosofía del juego de ataque contra diferentes Sistemas Defensivos tiene una raíz basada en los Principios Tácticos Colectivos del Ataque que se orienta y apoya a nivel práctico en los medios tácticos colectivos. Las diferentes estructuras colectivas en defensa exigen cumplir aquellos y saber elegir los medios tácticos adecuados. En síntesis, no existen "recetas" para resolver problemas sino la utilización de los medios tácticos adecuados. La estrategia tiene su fundamento y lleva al éxito siempre que se defina a partir de buenas bases tácticas. Palabras clave: Ataque, Defensa 6:0, Defensa 5.1 Abstract: The philosophy of the attack game against different Defensive Systems has a root based on the Principles Tactical Communities of the Attack that it is guided and it supports at practical level in the collective tactical means. The different collective structures in defense demand to complete those and to know how to choose the appropriate tactical means. In synthesis, recipes don't exist to solve problems but the use of the appropriate tactical means. The strategy has its foundation and it takes to the success whenever he/she is defined starting from good tactical bases. Key words: Attacks, variant defensive 6:0, variant defensive 5:1.

  12. OPEN DATA FOR DISCOVERY SCIENCE.

    Science.gov (United States)

    Payne, Philip R O; Huang, Kun; Shah, Nigam H; Tenenbaum, Jessica

    2017-01-01

    The modern healthcare and life sciences ecosystem is moving towards an increasingly open and data-centric approach to discovery science. This evolving paradigm is predicated on a complex set of information needs related to our collective ability to share, discover, reuse, integrate, and analyze open biological, clinical, and population level data resources of varying composition, granularity, and syntactic or semantic consistency. Such an evolution is further impacted by a concomitant growth in the size of data sets that can and should be employed for both hypothesis discovery and testing. When such open data can be accessed and employed for discovery purposes, a broad spectrum of high impact end-points is made possible. These span the spectrum from identification of de novo biomarker complexes that can inform precision medicine, to the repositioning or repurposing of extant agents for new and cost-effective therapies, to the assessment of population level influences on disease and wellness. Of note, these types of uses of open data can be either primary, wherein open data is the substantive basis for inquiry, or secondary, wherein open data is used to augment or enrich project-specific or proprietary data that is not open in and of itself. This workshop is concerned with the key challenges, opportunities, and methodological best practices whereby open data can be used to drive the advancement of discovery science in all of the aforementioned capacities.

  13. Hubble 15 years of discovery

    CERN Document Server

    Lindberg Christensen, Lars; Kornmesser, M

    2006-01-01

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

  14. Smartphones: A Potential Discovery Tool

    Directory of Open Access Journals (Sweden)

    Wendy Starkweather

    2009-09-01

    Full Text Available The anticipated wide adoption of smartphones by researchers is viewed by the authors as a basis for developing mobile-based services. In response to the UNLV Libraries’ strategic plan’s focus on experimentation and outreach, the authors investigate the current and potential role of smartphones as a valuable discovery tool for library users.

  15. Translational medicine and drug discovery

    National Research Council Canada - National Science Library

    Littman, Bruce H; Krishna, Rajesh

    2011-01-01

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

  16. Structural Biology Guides Antibiotic Discovery

    Science.gov (United States)

    Polyak, Steven

    2014-01-01

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

  17. A Discovery Approach to Movement.

    Science.gov (United States)

    O'Hagin, Isabel B.

    1998-01-01

    Investigates the effects of the discovery approach to movement-based instruction on children's level of musicality. Finds that the students with the highest musicality were girls, demonstrated reflective movements and a personal sense of style while moving, and made sense of the music by organizing, categorizing, and developing movement ideas.…

  18. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

    activities as the potential discovery of elements heavier than uranium [5]. He drew this conclusion ... alkaline earth metals in the irradiation of uranium by neutrons) Hahn and Strassmann did. 458. Pramana – J. ... the production of active barium isotopes from uranium and thorium by neutron irradiation;. Proof of further active ...

  19. A Bitslice Implementation of Anderson's Attack on A5/1

    Science.gov (United States)

    Bulavintsev, Vadim; Semenov, Alexander; Zaikin, Oleg; Kochemazov, Stepan

    2018-03-01

    The A5/1 keystream generator is a part of Global System for Mobile Communications (GSM) protocol, employed in cellular networks all over the world. Its cryptographic resistance was extensively analyzed in dozens of papers. However, almost all corresponding methods either employ a specific hardware or require an extensive preprocessing stage and significant amounts of memory. In the present study, a bitslice variant of Anderson's Attack on A5/1 is implemented. It requires very little computer memory and no preprocessing. Moreover, the attack can be made even more efficient by harnessing the computing power of modern Graphics Processing Units (GPUs). As a result, using commonly available GPUs this method can quite efficiently recover the secret key using only 64 bits of keystream. To test the performance of the implementation, a volunteer computing project was launched. 10 instances of A5/1 cryptanalysis have been successfully solved in this project in a single week.

  20. Arthritis Genetics Analysis Aids Drug Discovery

    Science.gov (United States)

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

  1. 26 CFR 1.501(c)(5)-1 - Labor, agricultural, and horticultural organizations.

    Science.gov (United States)

    2010-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(c)(5)-1... those engaged in such pursuits, the improvement of the grade of their products, and the development of a higher degree of efficiency in their respective occupations. (b)(1) General rule. An organization is not...

  2. 26 CFR 31.3402(f)(5)-1 - Form and contents of withholding exemption certificates.

    Science.gov (United States)

    2010-04-01

    ... THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Collection of Income Tax at Source § 31.3402(f)(5)-1 Form and contents of... Internal Revenue Service (IRS). An employer may also download and print Form W-4 from the IRS Internet site...

  3. National Ignition Facility sub-system design requirements computer system SSDR 1.5.1

    International Nuclear Information System (INIS)

    Spann, J.; VanArsdall, P.; Bliss, E.

    1996-01-01

    This System Design Requirement document establishes the performance, design, development and test requirements for the Computer System, WBS 1.5.1 which is part of the NIF Integrated Computer Control System (ICCS). This document responds directly to the requirements detailed in ICCS (WBS 1.5) which is the document directly above

  4. Wangai et al., Afr. J. Infect. Dis. (2011) 5(1): 1 - 6 SENSITIVITY OF ...

    African Journals Online (AJOL)

    AJTCAM

    Wangai et al., Afr. J. Infect. Dis. (2011) 5(1): 1 - 6. 1. SENSITIVITY OF MICROSCOPY COMPARED TO MOLECULAR DIAGNOSIS OF P. FALCIPARUM: IMPLICATIONS ON MALARIA TREATMENT IN EPIDEMIC AREAS IN. KENYA. Laura Nyawira Wangai 1,2, Muriira Geoffrey Karau 3, Paul Nthakanio Njiruh 4, Omar Sabah 5 ...

  5. [Artificial Intelligence in Drug Discovery].

    Science.gov (United States)

    Fujiwara, Takeshi; Kamada, Mayumi; Okuno, Yasushi

    2018-04-01

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

  6. 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.

  7. Enteric Neurobiology: Discoveries and Directions.

    Science.gov (United States)

    Wood, Jackie D

    Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus.

  8. A quantum causal discovery algorithm

    Science.gov (United States)

    Giarmatzi, Christina; Costa, Fabio

    2018-03-01

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

  9. The discovery of immunoglobulin E.

    Science.gov (United States)

    Ribatti, Domenico

    2016-03-01

    The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Androgenetic alopecia: stress of discovery.

    Science.gov (United States)

    Passchier, Jan; Erdman, Jeroen; Hammiche, Fatima; Erdman, Ruud A M

    2006-02-01

    The psychological problems of men in the initial stages of alopecia androgenetica (hereditary male hair loss) have seldom been studied. We evaluated two groups of 80 men with alopecia androgenetica in Stages II to IV, indicating the amount of hair loss (overall N=160; for Group I: M=48 yr., SD=18.2; for Group II: M=50 yr., SD=18.0) who visited a dermatology clinic for benign dermatological complaints but not for hair loss, by questionnaires and interview, retrospectively. As predicted, hair problems were reported to be significantly greater overall at the moment of discovery of hair loss than later. About half of the men reported feeling annoyed to very annoyed about the discovery of hair loss. For those patients, provision of information by internet might facilitate a visit to the dermatologist.

  11. Cyber-Enabled Scientific Discovery

    International Nuclear Information System (INIS)

    Chan, Tony; Jameson, Leland

    2007-01-01

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

  12. 12 CFR 308.107 - Document discovery.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Document discovery. 308.107 Section 308.107... PRACTICE AND PROCEDURE General Rules of Procedure § 308.107 Document discovery. (a) Parties to proceedings... only through the production of documents. No other form of discovery shall be allowed. (b) Any...

  13. 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... voluntarily. (b) The ALJ, at a party's request, may order compulsory discovery described in paragraph (c) of... respect to an issue in the case; (3) The discovery request was not made primarily for the purposes of...

  14. 42 CFR 426.532 - Discovery.

    Science.gov (United States)

    2010-10-01

    ... purpose of this section, the term documents includes relevant information, reports, answers, records... § 426.532 Discovery. (a) General rule. If the Board orders discovery, the Board must establish a... or burdensome; or (iii) Will unduly delay the proceeding. (c) Types of discovery available. A party...

  15. The discovery of the antiproton

    International Nuclear Information System (INIS)

    Chamberlain, Owen

    1989-01-01

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

  16. Model organisms and target discovery.

    Science.gov (United States)

    Muda, Marco; McKenna, Sean

    2004-09-01

    The wealth of information harvested from full genomic sequencing projects has not generated a parallel increase in the number of novel targets for therapeutic intervention. Several pharmaceutical companies have realized that novel drug targets can be identified and validated using simple model organisms. After decades of service in basic research laboratories, yeasts, worms, flies, fishes, and mice are now the cornerstones of modern drug discovery programs.: © 2004 Elsevier Ltd . All rights reserved.

  17. Gas reserves, discoveries and production

    International Nuclear Information System (INIS)

    Saniere, A.

    2006-01-01

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

  18. 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.

  19. Discovery of a Makemakean Moon

    Science.gov (United States)

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

    2016-01-01

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

  20. A New Universe of Discoveries

    Science.gov (United States)

    Córdova, France A.

    2016-01-01

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

  1. Study on the Focal Mechanism of the M5.1 Badong Earthquake in Hubei

    Directory of Open Access Journals (Sweden)

    Chen Junhua

    2014-02-01

    Full Text Available The focal mechanism solutions of the M5. 1 Badong earthquake and subsequent 34 aftershocks at ML 2. 0 or more were calculated using the P-wave first motion method; the main earthquake was normal fault dip slip type, and the slip types of the seismogenic rupture surfaces of the subsequent aftershocks primarily include normal dip slip (14 times, reverse dip slip (9 times, normal strike slip (9 times and reverse strike slip (2 times. The M5. 1 Badong earthquake activities may be related to the stress adjustment caused by the rise of the groundwater level and the decrease of the frictional resistance betvveen structural planes of rock formations due to the effect of reservoir water penetration, and related to the joint activities of the NE-strike Gaoqiao fault and the near EW-strike Daping fault.

  2. Demonstration of 5.1 Tbit/s data capacity on a single-wavelength channel

    DEFF Research Database (Denmark)

    Mulvad, Hans Christian Hansen; Galili, Michael; Oxenløwe, Leif Katsuo

    2010-01-01

    We have generated a single-wavelength data signal with a data capacity of 5.1 Tbit/s. The enabling techniques to generate the data signal are optical time-division multiplexing up to a symbol rate of 1.28 Tbaud, differential quadrature phase shift keying as data format, and polarisation......-multiplexing. For the first time, error-free performance with a bit error rate less than 1e-9 is demonstrated for the 5.1 Tbit/s data signal. This is achieved in a back-to-back configuration using a direct detection receiver based on polarisation- and time-demultiplexing, delay-demodulation and balanced photo-detection....

  3. Demonstration of 5.1 Tbit/s data capacity on a single-wavelength channel.

    Science.gov (United States)

    Hansen Mulvad, Hans Christian; Galili, Michael; Oxenløwe, Leif K; Hu, Hao; Clausen, Anders T; Jensen, Jesper B; Peucheret, Christophe; Jeppesen, Palle

    2010-01-18

    We have generated a single-wavelength data signal with a data capacity of 5.1 Tbit/s. The enabling techniques to generate the data signal are optical time-division multiplexing up to a symbol rate of 1.28 Tbaud, differential quadrature phase shift keying as data format, and polarisation-multiplexing. For the first time, error-free performance with a bit error rate less than 10(-9) is demonstrated for the 5.1 Tbit/s data signal. This is achieved in a back-to-back configuration using a direct detection receiver based on polarisation- and time-demultiplexing, delay-demodulation and balanced photo-detection.

  4. JPRS Report, China, Qiushi Seeking Truth, No. 5, 1 March 1991.

    Science.gov (United States)

    1991-05-09

    bribes , problem. Just as Comrade Jiang Zemin pointed out, "if corruption , theft, and pilferage, in reality they belong to the reform of the...corectly real estate business and the construction trade and will classified as corruption and acceptance of bribes . Hence, truly solve the problem of...JPRS-CAR-91-026 9 MAY 1991 ANNIVESUMMER 1941 - 1991 ,PRS Report- China QIUSHI [SEEKING TRUTH] No 5, 1 March 1991 REPRODUCED BY U S. DEPARTMENT OF

  5. IMPLEMENTASI SISTEM PENGENALAN SUARA MENGGUNAKAN SAPI 5.1 DAN DELPHI 5

    Directory of Open Access Journals (Sweden)

    Agustinus Noertjahyana

    2003-01-01

    Full Text Available Nowadays, speech recognition in computer application is not new topic. Speech recognition research is still in active area with purpose to get fast and accurate result. One of the famous speech recognition research is done by Microsoft Corporation which developed for Windows platform. Also Microsoft develop standard for speech recognition engine, namely SAPI (Speech Application Programming Interface which now get into version 5.1. Using SAPI, programmer can implement speech recognition using any kind of speech recognition engine and also can change the engine without consider for changing the program code. In this paper, we implement speech recognition system using SAPI 5.1, Microsoft Speech Engine and Delphi 5 as programming language to create text application for English dictation. Abstract in Bahasa Indonesia : Sekarang ini pengenalan pembicaraan pada aplikasi komputer bukan merupakan hal yang baru. Banyak penelitian yang telah dan sedang dilakukan untuk mendapatkan pengenalan pembicaraan yang cepat dan akurat. Salah satu yang terkenal adalah penelitian yang dilakukan oleh Microsoft Corporation yang dikembangkan untuk sistem operasi Windows. Selain mengembangkan engine pengenalan pembicaraan, Microsoft juga mengembangkan standard untuk pengenalan pembicaraan yaitu SAPI (Speech Application Programming Interface yang sekarang sudah mencapai versi 5.1. Dengan adanya SAPI memungkinkan pembuat aplikasi untuk mengimplementasikan sistem pengenalan pembicaraan dengan menggunakan engine sesuai yang diinginkan dan dapat mengganti penggunaan dari satu engine ke engine yang lain tanpa merubah aplikasi yang telah dibuat. Penelitian ini mengimplementasikan sistem pengenalan pembicaraan dengan menggunakan SAPI 5.1, Microsoft Speech Engine dan bahasa pemrograman Delphi 5 yang digunakan untuk melakukan diktasi berbahasa Inggris pada aplikasi berbasis teks. Kata kunci: Pengenalan suara, SAPI.

  6. AIDE Project: Deliverable D5.1 (Software Library for indoor location) and referenced documents

    OpenAIRE

    Amat, Guillermo

    2017-01-01

    This publication includes the Deliverable 5.1 (Software Library for indoor location) of the AIDE Project (G.A.645322) and the following documents that are referenced in the deliverable: [1] Zed AIDE Research & Development Team (2016). Indoor Mapping Guide. [2] Zed AIDE Research & Development Team (2016). AIDE Location Services. [3] Zed AIDE Research & Development Team (2016). AIDE YARP Wrapper for Location Services. [4] Zed AIDE Research & Development Team (2016). AIDE Contextual...

  7. Z-pinch implosion for ICF physics study on Angara-5-1

    International Nuclear Information System (INIS)

    Branitsky, A. V.; Fedulov, M. V.; Grabovsky, E. V.; Nedoseev, S. L.; Olejinik, G. M.; Smirnov, V. P.; Zakharov, S. V.

    1997-01-01

    Recent development of soft X-ray sources based on super-fast Z-pinch implosion has demonstrated the great promise of pulsed power for ICF physics study. The main direction of the 'Angara-5-1' program is oriented toward using the double liner scheme to confine radiation inside a cavity in order to enhance its intensity significantly. Collision of the external liner shell onto the inner leads to radiation penetration through the inner liner and a decrease in the radiation pulse duration to 3-5 ns. Testing this scheme on 'Angara-5-1' with current 3.5-5 MA demonstrates a flux intensity up to 3 TW/cm 2 . In spite of the fact that results of the experiment and a 1D-simulation are close, there are many issues with external liner stability during current sheath formation and implosion. Recent experimental efforts on Angara-5-1 focused on the 'cold start' problem and on the Rayleigh-Taylor instability for thick (gas-puff) and thin (doped foam) shells. Preionization makes the liner's plasma more homogeneous. The method also works in a plasma focus, according to the first results of a joint Polish-Russian experiment. A high current convolute increases ANGARA-5's load current from about 4 MA to 5.8 MA, which moves the radiation temperature toward the region of interest. We also outline a new approach to a generator intended to produce tens of MA, ANGARA-5-2

  8. GEMPAK 5.1 - A GENERAL METEOROLOGICAL PACKAGE (VAX VMS VERSION)

    Science.gov (United States)

    Des, Jardins M. L.

    1994-01-01

    GEMPAK is a general meteorological software package developed at NASA/Goddard Space Flight Center. It includes programs to analyze and display surface, upper-air, and gridded data, including model output. There are very general programs to list, edit, and plot data on maps, to display profiles and time series, to draw and fill contours, to draw streamlines, to plot symbols for clouds, sky cover, and pressure tendency, and draw cross sections in the case of gridded data and sounding data. In addition, there are Barnes objective analysis programs to grid surface and upper-air data. The programs include the capabilities to derive meteorological parameters from those found in the dataset, to perform vertical interpolations of sounding data to different coordinate systems, and to compute an extensive set of gridded diagnostic quantities by specifying various nested combinations of scalars and vector arithmetic, algebraic, and differential operators. The GEMPAK 5.1 graphics/transformation subsystem, GEMPLT, provides device-independent graphics. GEMPLT also has the capability to display output in a variety of map projections or overlaid on satellite imagery. GEMPAK 5.1 is written in FORTRAN 77 and C-language and has been implemented on VAX computers under VMS and on computers running the UNIX operating system. During installation and normal use, this package occupies approximately 100Mb of hard disk space. The UNIX version of GEMPAK includes drivers for several graphic output systems including MIT's X Window System (X11,R4), Sun GKS, PostScript (color and monochrome), Silicon Graphics, and others. The VMS version of GEMPAK also includes drivers for several graphic output systems including PostScript (color and monochrome). The VMS version is delivered with the object code for the Transportable Applications Environment (TAE) program, version 4.1 which serves as a user interface. A color monitor is recommended for displaying maps on video display devices. Data for rendering

  9. 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.

  10. DISCOVERY OF A MAKEMAKEAN MOON

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-01

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

  11. New vaccines: challenges of discovery.

    Science.gov (United States)

    Mahmoud, Adel

    2016-09-01

    Vaccines have been a major component of preventing and controlling infectious diseases. The basis for discovery of what protects is reviewed as well as new attempts in utilizing Reverse Vaccinology, RNA-RNA methods and proteome analysis are adding significantly to our knowledge. The challenge of how to define protective and defined components of microbes is still hampering efforts to discover new vaccines. Recent excitement about immunotherapy of cancer opens the way to develop vaccines against multiple malignancies. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  12. Scientific discovery using genetic programming

    DEFF Research Database (Denmark)

    Keijzer, Maarten

    2001-01-01

    in this work can be summarized as: The symbolic expressions produced by genetic programming can be made suitable for analysis and interpretation by using units of measurements to guide or restrict the search. To achieve this, the following has been accomplished: A standard genetic programming system...... that are numerically stable and correct. A case study using four real-world problems in the induction of dimensionally correct empirical equations on data using the two different methods is presented to illustrate to use and limitations of these methods in a framework of scientific discovery....

  13. The region of the supernova remnant MSH 15-52 revisited - A new thermal H II region, H II G 320.5-1.4

    Science.gov (United States)

    Lortet, M.-C.; Georgelin, Y. P.; Georgelin, Y. M.

    1987-06-01

    The authors revisited the stellar and nebular content in the direction of MSH 15-52. This search was initiated by the discovery of a new Hα thermal region H II G 320.5-1.4 with velocity VLSR = -43 km s-1, extending over an area similar to MSH 15-52, and clearly distinct from the foreground H II region BBW 28802. From a rediscussion of the reddening and distances of hot stars with available spectra in the direction l = 320°, it is found that they constitute a single stellar association (Cir OB1) at a distance about 4 kpc, probably not much more extended than 80×80 pc. This association contains the cluster Pis 20, four WR stars and a number of stars with ages in the range 4 - 10×106yr. It is the excitation source of H II G 320.5-1.4. In such an association, bubbles may have formed previously to the explosion of supernovae; also, several supernovae may have exploded recently. Thus it is not unlikely that MSH 15-52 originated from the same SN explosion as PSR 1509-58 and expanded freely into a bubble; on the other hand, it would not be surprising that two different supernovae exploded close in time and space.

  14. The Discovery of Artificial Radioactivity

    Science.gov (United States)

    Guerra, Francesco; Leone, Matteo; Robotti, Nadia

    2012-03-01

    We reconstruct Frédéric Joliot and Irène Curie's discovery of artificial radioactivity in January 1934 based in part on documents preserved in the Joliot-Curie Archives in Paris, France. We argue that their discovery followed from the convergence of two parallel lines of research, on the neutron and on the positron, that were focused on a well-defined experimental problem, the nuclear transmutation of aluminum and other light elements. We suggest that a key role was played by a suggestion that Francis Perrin made at the seventh Solvay Conference at the end of October 1933, that the alpha-particle bombardment of aluminum produces an intermediate unstable isotope of phosphorus, which then decays by positron emission. We also suggest that a further idea that Perrin published in December 1933, and the pioneering theory of beta decay that Enrico Fermi also first published in December 1933, established a new theoretical framework that stimulated Joliot to resume the researches that he and Curie had interrupted after the Solvay Conference, now for the first time using a Geiger-Müller counter to detect the positrons emitted when he bombarded aluminum with polonium alpha particles.

  15. ABODE IN HEAVEN: PAUL AND LIFE AFTER DEATH IN 2 CORINTHIANS 5:1-10

    Directory of Open Access Journals (Sweden)

    Verster, Pieter

    2016-12-01

    Full Text Available In 2 Corinthians 5:1-10, Paul uses different methods to explain his view on life after death. He uses the metaphors of a tent, a building, clothing and being at home with God. It is clear that Paul accepted that the future with God is certain and that he will receive a building from God in heaven even though he may die. There is life with God even before the final resurrection. A life of bliss is assured for those who believe in God.

  16. SCALE 5.1 Predictions of PWR Spent Nuclear Fuel Isotopic Compositions

    Energy Technology Data Exchange (ETDEWEB)

    Radulescu, Georgeta [ORNL; Gauld, Ian C [ORNL; Ilas, Germina [ORNL

    2010-03-01

    The purpose of this calculation report is to document the comparison to measurement of the isotopic concentrations for pressurized water reactor (PWR) spent nuclear fuel determined with the Standardized Computer Analysis for Licensing Evaluation (SCALE) 5.1 (Ref. ) epletion calculation method. Specifically, the depletion computer code and the cross-section library being evaluated are the twodimensional (2-D) transport and depletion module, TRITON/NEWT,2, 3 and the 44GROUPNDF5 (Ref. 4) cross-section library, respectively, in the SCALE .1 code system.

  17. A structural analysis of the A5/1 state transition graph

    Directory of Open Access Journals (Sweden)

    Andreas Beckmann

    2012-10-01

    Full Text Available We describe efficient algorithms to analyze the cycle structure of the graph induced by the state transition function of the A5/1 stream cipher used in GSM mobile phones and report on the results of the implementation. The analysis is performed in five steps utilizing HPC clusters, GPGPU and external memory computation. A great reduction of this huge state transition graph of 2^64 nodes is achieved by focusing on special nodes in the first step and removing leaf nodes that can be detected with limited effort in the second step. This step does not break the overall structure of the graph and keeps at least one node on every cycle. In the third step the nodes of the reduced graph are connected by weighted edges. Since the number of nodes is still huge an efficient bitslice approach is presented that is implemented with NVIDIA's CUDA framework and executed on several GPUs concurrently. An external memory algorithm based on the STXXL library and its parallel pipelining feature further reduces the graph in the fourth step. The result is a graph containing only cycles that can be further analyzed in internal memory to count the number and size of the cycles. This full analysis which previously would take months can now be completed within a few days and allows to present structural results for the full graph for the first time. The structure of the A5/1 graph deviates notably from the theoretical results for random mappings.

  18. Mcl-1 and YY1 inhibition and induction of DR5 by the BH3-mimetic Obatoclax (GX15-070) contribute in the sensitization of B-NHL cells to TRAIL apoptosis

    Science.gov (United States)

    Martínez-Paniagua, Melisa A; Baritaki, Stavroula; Huerta-Yepez, Sara; Ortiz-Navarrete, Vianney F; González-Bonilla, Cesar

    2011-01-01

    The pan Bcl-2 family antagonist Obatoclax (GX15-070), currently in clinical trials, was shown to sensitize TRAIL-resistant tumors to TRAIL-mediated apoptosis via the release of Bak and Bim from Mcl-1 or Bcl-2/Bcl-XL complexes or by the activation of Bax, though other mechanisms were not examined. Herein, we hypothesize that Obatoclax-mediated sensitization to TRAIL apoptosis may also result from alterations of the apoptotic pathways. The TRAIL-resistant B-cell line Ramos was used as a model for investigation. Treatment of Ramos cells with obatoclax significantly inhibited the expression of several members of the Bcl-2 family, dissociated Bak from Mcl-1 and inhibited the NFκB activity. Cells treated with Mcl-1 siRNA were sensitized to TRAIL apoptosis. We examined whether the sensitization of Ramos to TRAIL by Obatoclax resulted from signaling of the DR4 and/or DR5. Transfection with DR5 siRNA, but not with DR4 siRNA, sensitized the cells to apoptosis following treatment with Obatoclax and TRAIL. The signaling via DR5 correlated with Obatoclax-induced inhibition of the DR5 repressor Yin Yang 1 (YY1). Transfection with YY1 siRNA sensitized the cells to TRAIL apoptosis following treatment with Obatoclax and TRAIL. Overall, the present findings reveal a new mechanism of Obatoclax-induced sensitization to TRAIL apoptosis and the involvement of the inhibition of NFκB activity and downstream Mcl-1 and YY1 expressions and activities. PMID:21822052

  19. 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.

  20. Recent discoveries of anticancer flavonoids.

    Science.gov (United States)

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

    2017-12-15

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

  1. Transgenic parasites accelerate drug discovery

    Science.gov (United States)

    Rodriguez, Ana; Tarleton, Rick L.

    2013-01-01

    Parasitic neglected diseases are in dire need of new drugs either to replace old drugs rendered ineffective because of resistance development, to cover clinical needs that had never been addressed or to tackle other associated problems of existing drugs such as high cost, difficult administration, restricted coverage or toxicity. The availability of transgenic parasites expressing reporter genes facilitates the discovery of new drugs through high throughput screenings, but also by allowing rapid screening in animal models of disease. Taking advantage of these, we propose an alternative pathway of drug development for neglected diseases, going from high throughput screening directly into in vivo testing of the top ranked compounds selected by medicinal chemistry. Rapid assessment animal models allow for identification of compounds with bona fide activity in vivo early in the development chain, constituting a solid basis for further development and saving valuable time and resources. PMID:22277131

  2. The DOF transcription factor Dof5.1 influences leaf axial patterning by promoting Revoluta transcription in Arabidopsis

    KAUST Repository

    Kim, Hyungsae

    2010-10-05

    Dof proteins are transcription factors that have a conserved single zinc finger DNA-binding domain. In this study, we isolated an activation tagging mutant Dof5.1-D exhibiting an upward-curling leaf phenotype due to enhanced expression of the REV gene that is required for establishing adaxialabaxial polarity. Dof5.1-D plants also had reduced transcript levels for IAA6 and IAA19 genes, indicating an altered auxin biosynthesis in Dof5.1-D. An electrophoretic mobility shift assay using the Dof5.1 DNA-binding motif and the REV promoter region indicated that the DNA-binding domain of Dof5.1 binds to a TAAAGT motif located in the 5′-distal promoter region of the REV promoter. Further, transient and chromatin immunoprecipitation assays verified binding activity of the Dof5.1 DNA-binding motif with the REV promoter. Consistent with binding assays, constitutive over-expression of the Dof5.1 DNA-binding domain in wild-type plants caused a downward-curling phenotype, whereas crossing Dof5.1-D to a rev mutant reverted the upward-curling phenotype of the Dof5.1-D mutant leaf to the wild-type. These results suggest that the Dof5.1 protein directly binds to the REV promoter and thereby regulates adaxialabaxial polarity. © 2010 Blackwell Publishing Ltd.

  3. GeeWiz Integrated Visualization Interface for SCALE 5.1

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Stephen M [ORNL; Rearden, Bradley T [ORNL; Horwedel, James E [ORNL

    2007-01-01

    The KENO V.a and KENO-VI three-dimensional Monte Carlo criticality computer codes in the SCALE (Standardized Computer Analyses for Licensing Evaluation) computer software system developed at Oak Ridge National Laboratory (ORNL) are widely used and accepted around the world for criticality safety analyses. As part of current development efforts to improve SCALE's ease of use, the SCALE project team at ORNL has developed a new integrated graphical visualization package for KENO V.a and KENO-VI in SCALE 5.1. This package uses the SCALE Graphically Enhanced Editing Wizard (GeeWiz) as the visualization control center that provides users the capability to set up, execute, plot, and view results from KENO in a friendly, colorful, and interactive computing environment without ever using a text editor or a command prompt.

  4. Evaluation of the 2010 MODIS Collection 5.1 Land Cover Type Product over China

    Directory of Open Access Journals (Sweden)

    Tian Zeng

    2015-02-01

    Full Text Available Although the MODIS Collection 5.1 Land Cover Type (MODIS v5.1 LCT product is one of the most recent global land cover datasets and has the shortest updating cycle, evaluations regarding this collection have not been reported. Given the importance of evaluating global land cover data for producers and potential users, the 2010 MODIS v5.1 LCT product IGBP (International Geosphere-Biosphere Programme layer was evaluated based on two grid maps at scales of 100-m and 500-m,which were derived by rasterizing the 2010 data from the national land use/cover database of China (NLUD-C. This comparison was conducted based on a new legend consisting of nine classes constructed based on the definitions of classes in the IGBP and NLUD-C legends. The overall accuracies of the aggregated classification data were 64.62% and 66.42% at the sub-pixel and pixel scales, respectively. These accuracies differed significantly in different regions. Specifically, high-quality data were obtained more easily for regions with a single land cover type, such as Xinjiang province and the northeast plain of China. The lowest accuracies were obtained for the middle of China, including Ningxia, Shaanxi, Chongqing, Yunnan and Guizhou. At the sub-pixel scale, relatively high producer and user accuracies were obtained for cropland, grass and barren regions; the highest producer accuracy was obtained for forests, and the highest user accuracy was obtained for water bodies. Shrublands and wetlands were associated with low producer and user accuracies at the sub-pixel and pixel scales, of less than 10%. Based on dominant-type reference data, the errors were classified as mixed-pixel errors and labeling errors. Labeling errors primarily originated from misclassification between grassland and barren lands. Mixed pixel errors increased as the pixel diversity increased and as the percentage of dominant-type sub-pixels decreased. Overall, mixed pixels were sources of error for most land cover

  5. Assessing the State-of-the-Art in Dynamic Discovery of Ad Hoc Network Services

    Science.gov (United States)

    2001-07-18

    Cache Manager() 0..1 Contains 1 Contains SERVICE MANAGER discov er Network Context() <<not shr>> Cache Manager Discov ery () <<OPT>> Announce Serv ice...service availability requests Service Manager Service Cache Manager Service User Service Description Service Provider Service Repository Service...Group Service Manager Service User Service Cache Manager Aggressive Discovery Multicast Group SM4 SCM3 T ATT API GUI 20 30AddService50 SU8 5 1 2 S XYZ

  6. 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.…

  7. In silico discoveries for biomedical sciences

    NARCIS (Netherlands)

    Haagen, Herman van

    2011-01-01

    Text-mining is a challenging field of research initially meant for reading large text collections with a computer. Text-mining is useful in summarizing text, searching for the informative documents, and most important to do knowledge discovery. Knowledge discovery is the main subject of this thesis.

  8. Discovery and Innovation: About this journal

    African Journals Online (AJOL)

    Discovery and Innovation: About this journal. Journal Home > Discovery and Innovation: About this journal. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. People. » Contact ...

  9. 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 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery...

  10. Accounting for discovery bias in genomic prediction

    Science.gov (United States)

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

  11. 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 and Finance: Treasury Office of the Secretary of the Treasury PRACTICE BEFORE THE INTERNAL REVENUE... seeking the discovery through another source. (e) Failure to comply. Where a party fails to comply with an...

  12. False Discovery Rates and Multiple Testing

    Indian Academy of Sciences (India)

    IAS Admin

    RESONANCE | December 2013. GENERAL | ARTICLE. False Discovery Rates and Multiple Testing. Soumen Dey and Mohan Delampady. Keywords. False discovery rate, FDR,. pFDR, multiple testing, empiri- cal Bayes, hierarchical Bayes, high-dimensional problems. Soumen Dey is a research scholar at ISI, Bangalore.

  13. On Consistency Maintenance In Service Discovery

    NARCIS (Netherlands)

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

    2005-01-01

    Communication and node failures degrade the ability of a service discovery protocol to ensure Users receive the correct service information when the service changes. We propose that service discovery protocols employ a set of recovery techniques to recover from failures and regain consistency. We

  14. 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 HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.516 Discovery. (a) A party may make a request...

  15. 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 and Finance: Treasury Office of the Secretary of the Treasury REGULATIONS IMPLEMENTING THE PROGRAM... to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

  16. Service discovery in heterogeneous wireless networks

    NARCIS (Netherlands)

    Blangé, M.J.; Karkowski, I.P.; Vermeulen, B.C.B.

    2005-01-01

    In this paper we describe a possible solution to the problem of service discovery in heterogeneous wireless networks. This solution involves introduction of a network independent service discovery layer, with as main goal the improved robustness of applications running on top of it. A possible

  17. 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 Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS RULES OF... Congress, or the principles of common law. (e) Time limits. All discovery, including all responses to...

  18. 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.

  19. Study of Implosion of Twisted Nested Arrays at the Angara-5-1 Facility

    Science.gov (United States)

    Mitrofanov, K. N.; Zukakishvili, G. G.; Aleksandrov, V. V.; Grabovski, E. V.; Frolov, I. N.; Gribov, A. N.

    2018-01-01

    Results are presented from experimental studies of the implosion of twisted nested arrays in which the wires of the outer and inner arrays are twisted about the array axis in opposite directions (clockwise and counterclockwise). Experiments with twisted arrays were carried out at the Angara-5-1 facility at currents of up to 4 MA. The currents through the arrays were switched either simultaneously or the current pulse through the outer array was delayed by 10-15 ns with the help of an anode spark gap. It is shown that, in such arrays, the currents flow along the inclined wires and, accordingly, there are both the azimuthal and axial components of the discharge current. The process of plasma implosion in twisted arrays depends substantially on the value of the axial (longitudinal) magnetic field generated inside the array by the azimuthal currents. Two-dimensional simulations of the magnetic field in twisted nested arrays were performed in the ( r, z) geometry with allowance for the skin effect in the discharge electrodes. It is shown that, depending on the geometry of the discharge electrodes, different configurations of the magnetic field can be implemented inside twisted nested arrays. The calculated magnetic configurations are compared with the results of measurements of the magnetic field inside such arrays. It is shown that the configuration of the axial magnetic field inside a twisted nested array depends substantially on the distribution of the azimuthal currents between the inner and outer arrays.

  20. PIE on Safety-Tested AGR-1 Compact 5-1-1

    Energy Technology Data Exchange (ETDEWEB)

    Hunn, John D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Morris, Robert Noel [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Baldwin, Charles A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Montgomery, Fred C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gerczak, Tyler J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-08-01

    Post-irradiation examination (PIE) is being performed in support of tristructural isotropic (TRISO) coated particle fuel development and qualification for High-Temperature Gas-cooled Reactors (HTGRs). AGR-1 was the first in a series of TRISO fuel irradiation experiments initiated in 2006 under the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program; this work continues to be funded by the Department of Energy's Office of Nuclear Energy as part of the Advanced Reactor Technologies (ART) initiative. AGR-1 fuel compacts were fabricated at Oak Ridge National Laboratory (ORNL) in 2006 and irradiated for three years in the Idaho National Laboratory (INL) Advanced Test Reactor (ATR) to demonstrate and evaluate fuel performance under HTGR irradiation conditions. PIE is being performed at INL and ORNL to study how the fuel behaved during irradiation, and to examine fuel performance during exposure to elevated temperatures at or above temperatures that could occur during a depressurized conduction cooldown event. This report summarizes safety testing of irradiated AGR-1 Compact 5-1-1 in the ORNL Core Conduction Cooldown Test Facility (CCCTF) and post-safety testing PIE.

  1. Knowledge Discovery from Vibration Measurements

    Directory of Open Access Journals (Sweden)

    Jun Deng

    2014-01-01

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

  2. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

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

  3. Mathematical models in biological discovery

    CERN Document Server

    Walter, Charles

    1977-01-01

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

  4. NIF Discovery Science Eagle Nebula

    Science.gov (United States)

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

    2017-10-01

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

  5. Discovery Mondays: Zoom on materials

    CERN Multimedia

    2003-01-01

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

  6. Materials discovery through crystal growth

    Science.gov (United States)

    zur Loye, Hans-Conrad

    2016-04-01

    The discovery of new materials and associated desirable properties has been a driving force behind chemical innovation for centuries. When we look at some of the many recent technological advances, and how widespread and significant their impact has been, we appreciate how much they have relied on new materials. The increase in hard drive storage capacity due to new giant magneto-resistive materials, the ever-shrinking cell phone due to improved microwave dielectric materials, the enhancement in lithium battery storage capacity due to new intercalation materials, or the improved capacitor due to new ferroelectric materials are all excellent examples. How were these materials discovered? While there is no single answer, in all cases there was a First-Material, the archetype in which the phenomenon was first observed, the one that led to further investigations and the subsequent preparation of improved 2nd or 3rd generation materials. It is this First-Material, the archetype, that was discovered - often via crystal growth.

  7. The Discovery of Dabigatran Etexilate

    Directory of Open Access Journals (Sweden)

    Joanne evan Ryn

    2013-02-01

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

  8. Respiratory knowledge discovery utilising expertise

    Directory of Open Access Journals (Sweden)

    Tristan Ling

    2012-12-01

    Full Text Available BackgroundSignificant amounts of medical data are being archived, in the hope that they can be analysed and provide insight. A critical problem with analysing such data is the amount of existing knowledge required to produce effective results.AimsThis study tests a method that seeks to overcome these problems with analysis, by testing it over a large set of archived lung function test results. A knowledge base of lung function interpretation expertise has been compiled and serves as a base for analysis.MethodA user examines the dataset with the assistance of the knowledge discovery tool. Two pertinent respiratory research questions are analysed (the relative correlation between diffusing capacity and FEV1 or FVC bronchodilator response, and the effects of BMI on various parameters of lung function, and the results compared and contrasted with relevant literature.ResultsThe method finds interesting results from the lung function data supporting and questioning other published studies, while also finding correlations that suggest further areas of research.ConclusionWhile the analysis does not necessarily reveal groundbreaking information, it shows that the method can successfully discover new knowledge and is useful in a research context.

  9. Lysophospholipid receptors in drug discovery.

    Science.gov (United States)

    Kihara, Yasuyuki; Mizuno, Hirotaka; Chun, Jerold

    2015-05-01

    Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine 1-phospate (S1P), lysophosphatidylinositol (LPI), and lysophosphatidylserine (LysoPS), are bioactive lipids that transduce signals through their specific cell-surface G protein-coupled receptors, LPA1-6, S1P1-5, LPI1, and LysoPS1-3, respectively. These LPs and their receptors have been implicated in both physiological and pathophysiological processes such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, organismal development, and other effects on most organ systems. Advances in the LP receptor field have enabled the development of novel small molecules targeting LP receptors for several diseases. Most notably, fingolimod (FTY720, Gilenya, Novartis), an S1P receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis. This success is currently being followed by multiple, mechanistically related compounds targeting S1P receptor subtypes, which are in various stages of clinical development. In addition, an LPA1 antagonist, BMS-986020 (Bristol-Myers Squibb), is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis, as a distinct compound, SAR100842 (Sanofi) for the treatment of systemic sclerosis and related fibrotic diseases. This review summarizes the current state of drug discovery in the LP receptor field. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. West Nile Virus Drug Discovery

    Directory of Open Access Journals (Sweden)

    Siew Pheng Lim

    2013-12-01

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

  11. Students Excited by Stellar Discovery

    Science.gov (United States)

    2011-02-01

    In the constellation of Ophiuchus, above the disk of our Milky Way Galaxy, there lurks a stellar corpse spinning 30 times per second -- an exotic star known as a radio pulsar. This object was unknown until it was discovered last week by three high school students. These students are part of the Pulsar Search Collaboratory (PSC) project, run by the National Radio Astronomy Observatory (NRAO) in Green Bank, WV, and West Virginia University (WVU). The pulsar, which may be a rare kind of neutron star called a recycled pulsar, was discovered independently by Virginia students Alexander Snider and Casey Thompson, on January 20, and a day later by Kentucky student Hannah Mabry. "Every day, I told myself, 'I have to find a pulsar. I better find a pulsar before this class ends,'" said Mabry. When she actually made the discovery, she could barely contain her excitement. "I started screaming and jumping up and down." Thompson was similarly expressive. "After three years of searching, I hadn't found a single thing," he said, "but when I did, I threw my hands up in the air and said, 'Yes!'." Snider said, "It actually feels really neat to be the first person to ever see something like that. It's an uplifting feeling." As part of the PSC, the students analyze real data from NRAO's Robert C. Byrd Green Bank Telescope (GBT) to find pulsars. The students' teachers -- Debra Edwards of Sherando High School, Leah Lorton of James River High School, and Jennifer Carter of Rowan County Senior High School -- all introduced the PSC in their classes, and interested students formed teams to continue the work. Even before the discovery, Mabry simply enjoyed the search. "It just feels like you're actually doing something," she said. "It's a good feeling." Once the pulsar candidate was reported to NRAO, Project Director Rachel Rosen took a look and agreed with the young scientists. A followup observing session was scheduled on the GBT. Snider and Mabry traveled to West Virginia to assist in the

  12. Discoveries on the Norwegian continental shelf

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-02-01

    As discussed in this document, there are 108 discoveries on the Norwegian continental shelf which so far have not been approved for development. The oil and gas resources of the Norwegian Sea and the Barents Sea are mostly found in discoveries containing large volumes of gas. Eighty-one of the discoveries which are not approved for development are located in the North Sea and more than 60% of the discoveries in this province contain less than 5 mill Sm{sup 3} oil equivalents. In the Norwegian Sea and the Barents Sea there are 27 discoveries which are not approved for development and whose total resources are estimated at 500 mill Sm{sup 3} oil equivalents. About 60% of the oil resources is expected to be comprised by development plans in 1997 or 1998. Another 20% is in new discoveries currently being evaluated or in discoveries containing large volumes of gas. Production forecasts indicate substantial vacant oil processing capacity after 2000. Vacant gas processing capacity will mainly arise after 2005. 23 figs., 3 tabs.

  13. Functional Principles of Registry-based Service Discovery

    NARCIS (Netherlands)

    Sundramoorthy, V.; Tan, C.; Hartel, Pieter H.; den Hartog, Jeremy; Scholten, Johan

    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

  14. Thermal properties of PZT95/5(1.8Nb) and PSZT ceramics

    International Nuclear Information System (INIS)

    DiAntonio, Christopher Brian; Rae, David F.; Corelis, David J.; Yang, Pin; Burns, George Robert

    2006-01-01

    Thermal properties of niobium-modified PZT95/5(1.8Nb) and PSZT ceramics used for the ferroelectric power supply have been studied from -100 C to 375 C. Within this temperature range, these materials exhibit ferroelectric-ferroelectric and ferroelectric-paraelectric phase transformations. The thermal expansion coefficient, heat capacity, and thermal diffusivity of different phases were measured. Thermal conductivity and Grueneisen constant were calculated at several selected temperatures between -60 C and 100 C. Results show that thermal properties of these two solid solutions are very similar. Phase transformations in these ceramics possess first order transformation characteristics including thermal hysteresis, transformational strain, and enthalpy change. The thermal strain in the high temperature rhombohedral phase region is extremely anisotropic. The heat capacity for both materials approaches to 3R (or 5.938 cal/(g-mole*K)) near room temperature. The thermal diffusivity and the thermal conductivity are quite low in comparison to common oxide ceramics, and are comparable to amorphous silicate glass. Furthermore, the thermal conductivity of these materials between -60 C and 100 C becomes independent of temperature and is sensitive to the structural phase transformation. These phenomena suggest that the phonon mean free path governing the thermal conductivity in this temperature range is limited by the lattice dimensions, which is in good agreement with calculated values. Effects of small compositional changes and density/porosity variations in these ceramics on their thermal properties are also discussed. The implications of these transformation characteristics and unusual thermal properties are important in guiding processing and handling procedures for these materials

  15. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

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

  16. 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 ...

  17. The CNRM-CM5.1 global climate model: description and basic evaluation

    Science.gov (United States)

    Voldoire, A.; Sanchez-Gomez, E.; Salas y Mélia, D.; Decharme, B.; Cassou, C.; Sénési, S.; Valcke, S.; Beau, I.; Alias, A.; Chevallier, M.; Déqué, M.; Deshayes, J.; Douville, H.; Fernandez, E.; Madec, G.; Maisonnave, E.; Moine, M.-P.; Planton, S.; Saint-Martin, D.; Szopa, S.; Tyteca, S.; Alkama, R.; Belamari, S.; Braun, A.; Coquart, L.; Chauvin, F.

    2013-05-01

    A new version of the general circulation model CNRM-CM has been developed jointly by CNRM-GAME (Centre National de Recherches Météorologiques—Groupe d'études de l'Atmosphère Météorologique) and Cerfacs (Centre Européen de Recherche et de Formation Avancée) in order to contribute to phase 5 of the Coupled Model Intercomparison Project (CMIP5). The purpose of the study is to describe its main features and to provide a preliminary assessment of its mean climatology. CNRM-CM5.1 includes the atmospheric model ARPEGE-Climat (v5.2), the ocean model NEMO (v3.2), the land surface scheme ISBA and the sea ice model GELATO (v5) coupled through the OASIS (v3) system. The main improvements since CMIP3 are the following. Horizontal resolution has been increased both in the atmosphere (from 2.8° to 1.4°) and in the ocean (from 2° to 1°). The dynamical core of the atmospheric component has been revised. A new radiation scheme has been introduced and the treatments of tropospheric and stratospheric aerosols have been improved. Particular care has been devoted to ensure mass/water conservation in the atmospheric component. The land surface scheme ISBA has been externalised from the atmospheric model through the SURFEX platform and includes new developments such as a parameterization of sub-grid hydrology, a new freezing scheme and a new bulk parameterisation for ocean surface fluxes. The ocean model is based on the state-of-the-art version of NEMO, which has greatly progressed since the OPA8.0 version used in the CMIP3 version of CNRM-CM. Finally, the coupling between the different components through OASIS has also received a particular attention to avoid energy loss and spurious drifts. These developments generally lead to a more realistic representation of the mean recent climate and to a reduction of drifts in a preindustrial integration. The large-scale dynamics is generally improved both in the atmosphere and in the ocean, and the bias in mean surface temperature

  18. Queen's discovery lauded by top scientific journal

    CERN Multimedia

    McGrady, S

    2002-01-01

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

  19. Literature-Related Discovery: A Review

    National Research Council Canada - National Science Library

    Kostoff, Ronald N; Block, Joel A; Solka, Jeffrey L; Briggs, Michael B; Rushenberg, Robert L; Stump, Jesse A; Johnson, Dustin; Lyons, Terence J; Wyatt, Jeffrey R

    2007-01-01

    .... Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked to produce novel interesting, plausible, and intelligible knowledge (i.e...

  20. Specification Editing and Discovery Assistant Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The project will prototype a specification editing and discovery tool (SPEEDY) for C/C++ that will assist software developers with modular formal verification tasks...

  1. An introduction to web scale discovery systems.

    Science.gov (United States)

    Hoy, Matthew B

    2012-01-01

    This article explores the basic principles of web-scale discovery systems and how they are being implemented in libraries. "Web scale discovery" refers to a class of products that index a vast number of resources in a wide variety formats and allow users to search for content in the physical collection, print and electronic journal collections, and other resources from a single search box. Search results are displayed in a manner similar to Internet searches, in a relevance ranked list with links to online content. The advantages and disadvantages of these systems are discussed, and a list of popular discovery products is provided. A list of library websites with discovery systems currently implemented is also provided.

  2. Advances in synthetic peptides reagent discovery

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

    2013-05-01

    Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

  3. Discovery of Cyclic Peptide Estrogens and Antiestrogens

    National Research Council Canada - National Science Library

    Clark, Daniel

    2004-01-01

    The identification of proteins involved in the initiation of disease and the identification of small molecules that modulate these proteins are of great importance for the discovery of improved therapeutics...

  4. Discovery of Cyclic Peptide Estrogens and Antiestrogens

    National Research Council Canada - National Science Library

    Clark, Daniel

    2003-01-01

    Identification of proteins involved in the initiation of disease and the identification of small molecules that can modulate these proteins are of great importance towards the discovery of treatments...

  5. 42 CFR 1005.7 - Discovery.

    Science.gov (United States)

    2010-10-01

    ... OF EXCLUSIONS, CIVIL MONEY PENALTIES AND ASSESSMENTS § 1005.7 Discovery. (a) A party may make a... contained in this section will be interpreted to require the creation of a document, except that requested...

  6. Taxonomy Enabled Discovery (TED), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposal addresses the NASA's need to enable scientific discovery and the topic's requirements for: processing large volumes of data, commonly available on the...

  7. Reactions of 5-[1-(2-phenylmethylidene]-3-phenylimidazolidine-2,4-diones with some organometallic reagents

    Directory of Open Access Journals (Sweden)

    Teresa A. R. Akeng'a

    2005-06-01

    Full Text Available The reaction of Grignard reagents with 5-[1-(2-chlorophenylmethylidene]-3-phenylimidazolidine-2,4-dione, 4, and 5-[1-(2-bromophenylmethylidene]-3-phenylimidazolidine-2,4-dione, 5, gave exclusively 1,2-addition products, 6-8, in 70-80% yields. Lithium dibutylcuprate reacted with 4 to yield exclusively 1,2-addition product 9 (92%. No conjugate or 1,4-addition products were obtained. These results indicate that 5-[1-(2-phenylmethylidene]-3-phenylimidazolidine-2,4-diones do not react like normal unsaturated carbonyl compounds.

  8. Applying genetics in inflammatory disease drug discovery

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  9. The discovery of the structure of DNA

    Science.gov (United States)

    Squires, G. L.

    2003-04-01

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

  10. The Gozo discovery bus : a successful experiment

    OpenAIRE

    Vella, Maryrose

    2008-01-01

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

  11. Compound Data Mining for Drug Discovery.

    Science.gov (United States)

    Bajorath, Jürgen

    2017-01-01

    In recent years, there has been unprecedented growth in compound activity data in the public domain. These compound data provide an indispensable resource for drug discovery in academic environments as well as in the pharmaceutical industry. To handle large volumes of heterogeneous and complex compound data and extract discovery-relevant knowledge from these data, advanced computational mining approaches are required. Herein, major public compound data repositories are introduced, data confidence criteria reviewed, and selected data mining approaches discussed.

  12. Literature-Related Discovery: A Review

    Science.gov (United States)

    2007-11-05

    disaggregation; Guar Gum for decrease in plasma fibrinogen and viscosity; Cell hydration to improve cell deformity and increase arm blood flow. This...discoveries to insure that they were indeed unique. Some potential discoveries include: The use of plasmin to deter cell adhesion for use in non...2006] have generated a semantic space approach that bears some similarities to LSI. It is based on the Hyperspace Analogue to Language (HAL

  13. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

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

    2014-01-01

    cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline...... 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...

  14. Target discovery from data mining approaches.

    Science.gov (United States)

    Yang, Yongliang; Adelstein, S James; Kassis, Amin I

    2012-02-01

    Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (such as genes, proteins and miRNAs) to biological phenomena (such as molecular functions, pathways and phenotypes). Within the context of biomedical science, data mining refers to a bioinformatics approach that combines biological concepts with computer tools or statistical methods that are mainly used to discover, select and prioritize targets. In response to the huge demand of data mining for target discovery in the 'omics' era, this review explicates various data mining approaches and their applications to target discovery with emphasis on text and microarray data analysis. Two emerging data mining approaches, chemogenomic data mining and proteomic data mining, are briefly introduced. Also discussed are the limitations of various data mining approaches found in the level of database integration, the quality of data annotation, sample heterogeneity and the performance of analytical and mining tools. Tentative strategies of integrating different data sources for target discovery, such as integrated text mining with high-throughput data analysis and integrated mining with pathway databases, are introduced. Published by Elsevier Ltd.

  15. Insecticide discovery: an evaluation and analysis.

    Science.gov (United States)

    Sparks, Thomas C

    2013-09-01

    There is an on-going need for the discovery and development of new insecticides due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectrums, and changing agricultural practices. Since 1960, the number of research-based companies in the US and Europe involved in the discovery of new insecticidal chemistries has been declining. In part this is a reflection of the increasing costs of the discovery and development of new pesticides. Likewise, the number of compounds that need to be screened for every product developed has, until recently, been climbing. In the past two decades the agrochemical industry has been able to develop a range of new products that have more favorable mammalian vs. insect selectivity. This review provides an analysis of the time required for the discovery, or more correctly the building process, for a wide range of insecticides developed during the last 60 years. An examination of the data around the time requirements for the discovery of products based on external patents, prior internal products, or entirely new chemistry provides some unexpected observations. In light of the increasing costs of discovery and development, coupled with fewer companies willing or able to make the investment, insecticide resistance management takes on greater importance as a means to preserve existing and new insecticides. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Shuttle Discovery Landing at Edwards

    Science.gov (United States)

    1989-01-01

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

  17. The nuclear agreement between the P5+1 and Iran: real progress?

    International Nuclear Information System (INIS)

    Sitt, Bernard

    2013-11-01

    The joint plan of action signed on the 24 November 2013 by the P5+1 and Iran is good news, and all the States parties to this document have expressed their satisfaction. This 'mutually agreed long-term comprehensive solution' - as it is repeatedly referred to in the preamble - constitutes a concrete materialisation of the softening of Iran's position since the election of Hassan Rouhani as the country's president (with the approval of the Supreme Guide Ali Khamenei). This plan of action was adopted after nearly eleven years of a crisis that was interrupted on one occasion only by the Paris Agreement signed on the 15 November 2004 between the EU3 and Iran (whose chief negotiator at the time was Hassan Rouhani), and which took a more radical turn following Mahmoud Ahmadinejad's accession to power. But this text, written in the conditional tense, is not strictly speaking an agreement. It is rather an agreement on the substance of a future agreement, albeit a precise and detailed one. Negotiations will be carried out over an initial six-month period, and a second phase will finalise a full agreement at most one year on from the adoption of the joint action plan. It is also underlined that this agreement will be an indivisible whole: nothing will be agreed unless everything is agreed. The limitations that Iran is prepared to accept on its nuclear programme would appear to be substantial: the retention of half of its stock of 20%-enriched uranium to produce fuel for the Teheran Research Reactor and the dilution of the other half to no more than 5%; no increase in its existing enrichment capabilities, but it will continue its research and development practices in this field; the suspension of the construction of the Arak heavy-water reactor; no reprocessing; and enhanced monitoring of nuclear activities by the IAEA. In exchange, no new sanctions or crude oil embargoes will be imposed; existing sanctions on petrochemical products and services will

  18. Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by extracellular cations

    DEFF Research Database (Denmark)

    Søe, Rikke; Andreasen, Mogens; Klærke, Dan Arne

    2009-01-01

    This work demonstrates that extracellular Na(+) modulates the cloned inwardly rectifying K(+) channels Kir4.1 and Kir4.1-Kir5.1. Whole-cell patch clamp studies on astrocytes have previously indicated that inward potassium currents are regulated by external Na(+). We expressed Kir4.1 and Kir4.1-Kir5.......1 in Xenopus oocytes to disclose if Kir4.1 and/or Kir4.1-Kir5.1 at the molecular level are responsible for the observed effect of [Na(+)](o) and to investigate the regulatory mechanism of external cations further. Our results showed that Na(+) has a biphasic modulatory effect on both Kir4.1 and Kir4.1-Kir5.......1 currents. Depending on the Na(+)-concentration and applied voltage, the inward Kir4.1/Kir4.1-Kir5.1 currents are either enhanced or reduced by extracellular Na(+). The Na(+) activation was voltage-independent, whereas the Na(+)-induced reduction of the Kir4.1 and Kir4.1-Kir5.1 currents was both...

  19. 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.

  20. Internet Naming and Discovery Architecture and Economics

    CERN Document Server

    Khoury, Joud S

    2013-01-01

    Naming is an integral building block within data networks and systems and is becoming ever more important as complex data-centric usage models emerge. Internet Naming and Discovery is timely in developing a unified model for studying the topic of naming and discovery. It details the architectural and economic tools needed for designing naming and discovery schemes within the broader context of internetwork architecture.   Readers will find in this book a historic overview of the Internet and a comprehensive survey of the literature, followed by and an in-depth examination of naming and discovery. Specific topics covered include: ·         formal definitions of name, address, identifier, locator, binding, routing, discovery, mapping, and resolution; ·         a discussion of the properties of names and bindings, along with illustrative case studies; ·         taxonomy that helps in organizing the solution space, and more importantly in identifying new avenues for contributing to the...

  1. The Discovery of Subatomic Particles Revised Edition

    Science.gov (United States)

    Weinberg, Steven

    2003-09-01

    This commentary on the discovery of the atom's constituents provides an historical account of key events in the physics of the twentieth century that led to the discoveries of the electron, proton and neutron. Steven Weinberg introduces the fundamentals of classical physics that played crucial roles in these discoveries. Connections are shown throughout the book between the historic discoveries of subatomic particles and contemporary research at the frontiers of physics, including the most current discoveries of new elementary particles. Steven Weinberg was Higgins Professor of Physics at Harvard before moving to The University of Texas at Austin, where he founded its Theory Group. At Texas he holds the Josey Regental Chair of Science and is a member of the Physics and Astronomy Departments. His research has spanned a broad range of topics in quantum field theory, elementary particle physics, and cosmology, and has been honored with numerous awards, including the Nobel Prize in Physics, the National Medal of Science, the Heinemann Prize in Mathematical Physics, the Cresson Medal of the Franklin Institute, the Madison Medal of Princeton University, and the Oppenheimer Prize. In addition to the well-known treatise, Gravitation and Cosmololgy, he has written several books for general readers, including the prize-winning The First Three Minutes (now translated into 22 foreign languages), and most recently Dreams of a Final Theory (Pantheon Books, 1993). He has also written a textbook The Quantum Theory of Fields, Vol.I, Vol. II, and Vol. III (Cambridge).

  2. Lifeomics leads the age of grand discoveries.

    Science.gov (United States)

    He, Fuchu

    2013-03-01

    When our knowledge of a field accumulates to a certain level, we are bound to see the rise of one or more great scientists. They will make a series of grand discoveries/breakthroughs and push the discipline into an 'age of grand discoveries'. Mathematics, geography, physics and chemistry have all experienced their ages of grand discoveries; and in life sciences, the age of grand discoveries has appeared countless times since the 16th century. Thanks to the ever-changing development of molecular biology over the past 50 years, contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be 'lifeomics'. At the end of the 20th century, genomics wrote out the 'script of life'; proteomics decoded the script; and RNAomics, glycomics and metabolomics came into bloom. These 'omics', with their unique epistemology and methodology, quickly became the thrust of life sciences, pushing the discipline to new high. Lifeomics, which encompasses all omics, has taken shape and is now signalling the dawn of a new era, the age of grand discoveries.

  3. SM5-1-conjugated PLA nanoparticles loaded with 5-fluorouracil for targeted hepatocellular carcinoma imaging and therapy.

    Science.gov (United States)

    Ma, Xibo; Cheng, Zhen; Jin, Yushen; Liang, Xiaolong; Yang, Xin; Dai, Zhifei; Tian, Jie

    2014-03-01

    SM5-1 is a humanized mouse antibody which has a high binding specificity for a membrane protein of about 230 kDa overexpressed in hepatocellular carcinoma (HCC), melanoma and breast cancer. In this study, SM5-1-conjugated poly D, L (lactide-coglycolide) (PLA) PLA containing Cy7 (PLA-Cy7-SM5-1) was prepared to study the targeting specificity of the bioconjugate to HCC-LM3-fLuc cell. Then, SM5-1-conjugated PLA containing 5-fluorouracil (5-FU) (PLA-5FU-SM5-1) and PLA containing 5-FU (PLA-5FU) were prepared for treatment of subcutaneous HCC-LM3-fLuc tumor mice. The results showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 45.07%, 23.56% and 19.05% tumor growth inhibition rate, respectively, on day 31 post-treatment as determined by bioluminescent intensity. In addition, in order to evaluate the antitumor efficacy of PLA-5FU-SM5-1, HCC-LM3-fLuc cells were injected into the liver to establish the experimental orthotopic liver tumor models. The experiments showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 53.24%, 31.00%, and 18.11% tumor growth inhibition rate, respectively, on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, we have calculated the three-dimensional location of the liver cancer in mice using a multilevel adaptive finite element algorithm based on bioluminescent intensity decay calibration. The reconstruction results demonstrated that PLA-5FU-SM5-1 inhibited the tumor rapid progression, which were consistent with the results of subcutaneous tumor mice experiments and in vitro cell experiment results. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Context-sensitive service discovery experimental prototype and evaluation

    DEFF Research Database (Denmark)

    Balken, Robin; Haukrogh, Jesper; L. Jensen, Jens

    2007-01-01

    the network in domains that handle the complex distributed service discovery, which is based on dynamically changing context information. In the prototype, a method for performing context-sensitive service discovery has been realised. The service discovery part utilizes UPnP, which has been expanded in order...... to increase network scalability. The experimental analysis of service discovery times for different scenarios is used to optimize parameter settings of the service discovery system in order to achieve short response times....

  5. Nephritogenic mAb 5-1-6 is directed at the extracellular domain of rat nephrin

    Science.gov (United States)

    Topham, Peter S.; Kawachi, Hiroshi; Haydar, Samir A.; Chugh, Sumant; Addona, Theresa A.; Charron, Kathryn B.; Holzman, Lawrence B.; Shia, Michael; Shimizu, Fujio; Salant, David J.

    1999-01-01

    mAb 5-1-6 identifies an antigen on rat podocyte slit-diaphragms and induces severe proteinuria when injected into rats. Nephrin, an Ig-like transmembrane protein that is mutated in congenital nephrotic syndrome of the Finnish type, has been localized to the slit-diaphragm on human podocytes. Here we document that the mAb 5-1-6 antigen is rat nephrin. After incubation of rat glomeruli with this mAb, the antibody/antigen complex was chemically cross-linked, extracted, and immunoprecipitated, prior to Western analysis. By mass spectrometry and 2D gel electrophoresis, we identified several peptides with complete identity to human nephrin. In addition, the 185-kDa protein immunoprecipitated by mAb 5-1-6 from rat glomerular extracts reacts with a rabbit anti-mouse nephrin antibody. Finally, nephrin and the mAb 5-1-6 antigen have identical glomerular localization patterns on immunofluorescence of rat kidney. These results demonstrate that the nephritogenic mAb 5-1-6 identifies the extracellular domain of nephrin, thereby documenting the importance of the slit-diaphragm and its component, nephrin, in the regulation of glomerular permselectivity. J. Clin. Invest. 104:1559–1566 (1999). PMID:10587519

  6. Bioinformatics for discovery of microbiome variation

    DEFF Research Database (Denmark)

    Brejnrod, Asker Daniel

    two conditions. The purpose is to assess the false discovery rate, recovery of truly differential abundant bacteria and the impact of beta diversity exploration strategies commonly used in microbiome research. We assess these differences by simulation and by making biological assumptions about...... 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...... 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...

  7. A perfect launch of Space Shuttle Discovery

    Science.gov (United States)

    2000-01-01

    Space Shuttle Discovery lifts off Launch Pad 39A against a backdrop of xenon lights (just above the orbiter' nose and at left). On the Mobile Launcher Platform beneath, water begins flooding the area for flame and sound control. The perfect on- time liftoff occurred at 7:17 p.m. EDT, sending a crew of seven on the 100th launch in the history of the Shuttle program. Discovery carries a payload that includes the Integrated Truss Structure Z-1, first of 10 trusses that will form the backbone of the Space Station, and the third Pressurized Mating Adapter that will provide a Shuttle docking port for solar array installation on the sixth Station flight and Lab installation on the seventh Station flight. Discovery's landing is expected Oct. 22 at 2:10 p.m. EDT.

  8. John Herschel on the Discovery of Neptune

    Science.gov (United States)

    Kollerstrom, Nicholas

    2006-12-01

    The letters of John Herschel that concern the discovery of the planet Neptune have not been greatly discussed by historians of science. I have transcribed these in the course of archiving the British Neptune-discovery documents. Herschel tends to be depicted as a background figure in narrations of the story of Neptune's discovery, whereas the present account focuses upon his evolving view of the topic: the rival merits of the two main protagonists, and the startling manner in which an obscure branch of mathematics (perturbation theory) was able to pinpoint the position of a new sphere in the sky. As the son of the man who found Uranus, his views have a special relevance. Also, I suggest that his eloquent prose style may still be enjoyed today.

  9. Virtual drug discovery: beyond computational chemistry?

    Science.gov (United States)

    Gilardoni, Francois; Arvanites, Anthony C

    2010-02-01

    This editorial looks at how a fully integrated structure that performs all aspects in the drug discovery process, under one company, is slowly disappearing. The steps in the drug discovery paradigm have been slowly increasing toward virtuality or outsourcing at various phases of product development in a company's candidate pipeline. Each step in the process, such as target identification and validation and medicinal chemistry, can be managed by scientific teams within a 'virtual' company. Pharmaceutical companies to biotechnology start-ups have been quick in adopting this new research and development business strategy in order to gain flexibility, access the best technologies and technical expertise, and decrease product developmental costs. In today's financial climate, the term virtual drug discovery has an organizational meaning. It represents the next evolutionary step in outsourcing drug development.

  10. Discovery, Characterization, and Dynamics of Transiting Exoplanets

    DEFF Research Database (Denmark)

    Van Eylen, Vincent

    2015-01-01

    Are we alone in the Universe? So far, the question remains unanswered, but a significant leap forward was achieved two decades ago, with the discovery of the first planets orbiting stars other than our Sun. Almost 2000 exoplanets have now been detected. They are diverse in radius, mass and orbital......, in this thesis I make use of the transit method, which is based on the observed brightness drop of a star as a planet crosses in front of it. This thesis consists of two parts. The first part focuses on the discovery of new planets and the understanding of exoplanet properties. I report the discovery...... results of this study, constraining the masses and bulk compositions of three planets. The second part of this thesis focuses on dynamics of exoplanets. All the solar system planets orbit in nearly the same plane, and that plane is also aligned with the equatorial plane of the Sun. That is not true...

  11. Protein chemical synthesis in drug discovery.

    Science.gov (United States)

    Liu, Fa; Mayer, John P

    2015-01-01

    The discovery of novel therapeutics to combat human disease has traditionally been among the most important goals of research chemists. After a century of innovation, state-of-the-art chemical protein synthesis is now capable of efficiently assembling proteins of up to several hundred residues in length from individual amino acids. By virtue of its unique ability to incorporate non-native structural elements, chemical protein synthesis has been seminal in the recent development of several novel drug discovery technologies. In this chapter, we review the key advances in peptide and protein chemistry which have enabled our current synthetic capabilities. We also discuss the synthesis of D-proteins and their applications in mirror image phage-display and racemic protein crystallography, the synthesis of enzymes for structure-based drug discovery, and the direct synthesis of homogenous protein pharmaceuticals.

  12. Neutron Diffraction and Inorganic Materials Discovery

    International Nuclear Information System (INIS)

    Rosseinsky, M.J.

    2005-01-01

    Full text: The discovery of complex inorganic materials is an important academic and technological challenge because of the opportunities these systems offer for observation of new phenomena, and the questions they pose for fundamental understanding. This presentation will illustrate the key role of neutron powder diffraction in enabling the discovery of new classes of materials, and in evaluating their properties and the conditions under which they need to be processed to optimise their behaviour in devices for applications. New chemistry is illustrated by the transition metal oxide hydrides, where both structure and ionic mobility required neutron scattering characterisation. The relationship between chemistry, structure and properties will be addressed by considering the difficulties in inducing superconductivity in analogues of magnesium diboride. The role of both neutron and X-ray diffraction in evaluating the processing of microwave dielectric ceramics will be highlighted, with the discovery of new phases shown to be a useful bonus in this type of in-situ study. (author)

  13. 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.

  14. From the nucleus discovery to DWBA

    International Nuclear Information System (INIS)

    Fernandez, B.

    2007-01-01

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

  15. The discovery of the tau lepton

    International Nuclear Information System (INIS)

    Perl, M.L.

    1992-09-01

    The discovery of the tau lepton and the third generation of fermions came from the convergence of three physics streams in the late 1960's and early 1970's. These streams were: the failed attempts by myself and others to understand the connection between the electron and the muon, the development of electron-positron storage rings, and the development of the theory of sequential leptons. In this paper I give the history of the discovery of the tau and the measurement of its major properties-the properties which established the tau as a sequential lepton

  16. Net present value approaches for drug discovery.

    Science.gov (United States)

    Svennebring, Andreas M; Wikberg, Jarl Es

    2013-12-01

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

  17. Antibacterial drug discovery in the resistance era.

    Science.gov (United States)

    Brown, Eric D; Wright, Gerard D

    2016-01-21

    The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.

  18. The centenary of discovery of radium

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  19. The discovery of elements 113 to 118

    Directory of Open Access Journals (Sweden)

    Utyonkov Vladimir

    2016-01-01

    Full Text Available Discovery and investigation of the “Island of stability” of superheavy nuclei at the separator DGFRS in the 238U-249Cf+ 48Ca reactions is reviewed. The results are compared with the data obtained in chemistry experiments and at the separators SHIP, BGS, TASCA, and GARIS. The synthesis of the heaviest nuclei, their decay properties, and methods of identification are discussed and compared with the criteria that must be satisfied for claiming the discovery of a new chemical element. The role of shell effects in the stability of superheavy nuclei is demonstrated by comparison of the experimental results with empirical systematics and theoretical data.

  20. 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...... based on their cardinality and duration, and the top-$k$ groups are returned. To avoid returning similar subgroups in a result, notions of domination and similarity are introduced that enable the pruning of low-interest groups. Empirical studies on real and synthetic data sets offer insight...

  1. Using Discovery Learning to Encourage Creative Thinking

    Directory of Open Access Journals (Sweden)

    Mardia Hi. Rahman

    2017-10-01

    Full Text Available Creative thinking ability development is needed to be implemented by every educator including lecturers to their students. Therefore, they need to seriously act and design their learning process. One of the ways to develop student’s creative thinking is using discovery learning model. This research is conducted in physics education study program in 2016 with students who took learning and teaching class as research subject. From the research analysis result and discussion, it can be concluded that discovery learning model can encourage students’ creative thinking ability in learning and teaching strategy subject.

  2. Ancistrotanzanine C and related 5,1 '- and 7,3 '-coupled naphthylisoquinoline alkaloids from Ancistrocladus tanzaniensis

    DEFF Research Database (Denmark)

    Bringmann, G.; Dreyer, M.; Faber, J.H.

    2004-01-01

    Three new naphthylisoquinoline alkaloids, the 7,3'-coupled ancistrotanzanine C (6), the 5,1'-coupled O-methylancistrocladinine (7), and the likewise 5,1'-coupled O,N-dimethylancistrocladine (8, previously known only as a partial-synthetic compound), have been isolated from the highland liana...... Ancistrocladus tanzaniensis, along with the two known 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (4) and ancistrotectorine (5). All of the compounds are S-configured at C-3 and bear an oxygen at C-6, and thus belong to the so-called Ancistrocladaceae type, similar to 1-3 previously isolated...

  3. A framework for expanding aqueous chemistry in the Community Multiscale Air Quality (CMAQ) model version 5.1

    Science.gov (United States)

    This paper describes the development and implementation of an extendable aqueous-phase chemistry option (AQCHEM − KMT(I)) for the Community Multiscale Air Quality (CMAQ) modeling system, version 5.1. Here, the Kinetic PreProcessor (KPP), version 2.2.3, is used t...

  4. Genealogies and spiritualities in Genesis 4:17-22, 4:25-26, 5:1-32 ...

    African Journals Online (AJOL)

    The three genealogies in Genesis 4:17-22, 4:25-26 en 5:1-32 show different intentions: the first wants (amongst other purposes) to give an aetiology of the trades; the second wants to stress the importance of a new beginning; the third wants to relate Adam to Noah. Each of these approaches to genealogy has a different ...

  5. Project Ice Storm: Prenatal Maternal Stress Affects Cognitive and Linguistic Functioning in 5 1/2-Year-Old Children

    Science.gov (United States)

    Laplante, David P.; Brunet, Alain; Schmitz, Norbert; Ciampi, Antonio; King, Suzanne

    2008-01-01

    The study used data from Project Ice Storm to determine the extent to which exposure to prenatal maternal stress due to a natural disaster can explain variance in the intellectual and language performance of offspring at age 5 1/2.

  6. The effects of 5.1 sound presentations on the perception of stereoscopic imagery in video games

    Science.gov (United States)

    Cullen, Brian; Galperin, Daniel; Collins, Karen; Hogue, Andrew; Kapralos, Bill

    2013-03-01

    Stereoscopic 3D (S3D) content in games, film and other audio-visual media has been steadily increasing over the past number of years. However, there are still open, fundamental questions regarding its implementation, particularly as it relates to a multi-modal experience that involves sound and haptics. Research has shown that sound has considerable impact on our perception of 2D phenomena, but very little research has considered how sound may influence stereoscopic 3D. Here we present the results of an experiment that examined the effects of 5.1 surround sound (5.1) and stereo loudspeaker setups on depth perception in relation to S3D imagery within a video game environment. Our aim was to answer the question: "can 5.1 surround sound enhance the participant's perception of depth in the stereoscopic field when compared to traditional stereo sound presentations?" In addition, our study examined how the presence or absence of Doppler frequency shift and frequency fall-off audio effects can also influence depth judgment under these conditions. Results suggest that 5.1 surround sound presentations enhance the apparent depth of stereoscopic imagery when compared to stereo presentations. Results also suggest that the addition of audio effects such as Doppler shift and frequency fall-off filters can influence the apparent depth of S3D objects.

  7. Burkholderia cenocepacia Strain CEIB S5-1, a Rhizosphere-Inhabiting Bacterium with Potential in Bioremediation

    OpenAIRE

    Mart?nez-Ocampo, Fernando; Lozano-Aguirre Beltr?n, Luis Fernando; Hern?ndez-Mendoza, Armando; Rojas-Espinoza, Luis Enrique; Popoca-Ursino, Elida Carolina; Ortiz-Hern?ndez, Mar?a Laura; S?nchez-Salinas, Enrique; Ramos Quintana, Fernando; Dant?n-Gonz?lez, Edgar

    2015-01-01

    Burkholderia cenocepacia is considered an opportunistic pathogen from humans and may cause disease in plants. A bioprospection from a plaguicide-contaminated agricultural field in Mexico identified several methyl parathion-degrading bacteria. Here, we report the draft genome sequence of B. cenocepacia strain CEIB S5-1, which gave us clues into ecological biodiversity.

  8. 10 CFR 2.1018 - Discovery.

    Science.gov (United States)

    2010-01-01

    ... production of, copies of documentary material for which bibliographic headers only have been submitted..., such as the names of witnesses and the subjects they plan to address; and (vii) Interrogatories and... depositions upon written questions may be authorized by order of the discovery master appointed under...

  9. Discovery Learning for Mathematical Literacy Ability

    Science.gov (United States)

    Tokada, D.; Herman, T.; Suhendra

    2017-09-01

    The background of this research is students’ mathematical literacy ability which is still less so most students find difficulty in solving mathematical problem in daily life. Learning which tend to be teacher centered not give change to students to develop their own ideas so the students do not master the concept well. Discovery learning is one of learning which train students how to discover mathematical concept and to train students to express their ideas. This study is quasi experimental study which is aimed to find out the enhancement of mathematical literacy ability of eighth grade students with discovery learning. This research used nonequivalent control group design. The population in this research were all students of the eight grade Junior High School in Tana Toraja. This research conclude that mathematics learning with discovery learning method in eight grade students of Junior High School can enhance the ability of mathematical literacy more significant. Discovery learning give change to students to construct their own knowledge so they can understand mathematical problem until its solution.

  10. Streaming Process Discovery and Conformance Checking

    DEFF Research Database (Denmark)

    Burattin, Andrea

    2018-01-01

    Streaming process discovery, streaming conformance checking, and streaming process mining in general (also known as online process mining) are disciplines which analyze event streams to extract a process model or to assess their conformance with respect to a given reference model. The main...

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

    Science.gov (United States)

    Bakker, Arthur

    2018-01-01

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

  12. The next generation of targeted mutation discovery

    NARCIS (Netherlands)

    Harakalova, M.

    2013-01-01

    Sequencing technologies (NGS) now allows efficient analysis of the complete protein-coding regions of genomes (exomes) for multiple samples in a single sequencing run. In Chapter 2, we present our results with a genomic DNA pooling strategy for rare variant discovery on a NGS platform. The high

  13. Bioenergy Knowledge Discovery Framework (KDF) Fact Sheet

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-07-29

    The Bioenergy Knowledge Discovery Framework (KDF) is an online collaboration and geospatial analysis tool that allows researchers, policymakers, and investors to explore and engage the latest bioenergy research. This publication describes how the KDF harnesses Web 2.0 and social networking technologies to build a collective knowledge system that facilitates collaborative production, integration, and analysis of bioenergy-related information.

  14. Discovery and preclinical development of new antibiotics.

    Science.gov (United States)

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

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

  15. 36 CFR 1150.63 - Discovery.

    Science.gov (United States)

    2010-07-01

    ... satisfactory to the judge, the judge may decide the fact or issue relating to the material requested to be... appropriate circumstances, but not as a matter of course, the judge may entertain motions for permission for... for discovery shall be granted only to the extent and upon such terms as the judge in his/her...

  16. Knowledge Discovery and Data Mining: An Overview

    Science.gov (United States)

    Fayyad, U.

    1995-01-01

    The process of knowledge discovery and data mining is the process of information extraction from very large databases. Its importance is described along with several techniques and considerations for selecting the most appropriate technique for extracting information from a particular data set.

  17. 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

  18. Natural product discovery: past, present, and future.

    Science.gov (United States)

    Katz, Leonard; Baltz, Richard H

    2016-03-01

    Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.

  19. Computational approaches to natural product discovery

    NARCIS (Netherlands)

    Medema, M.H.; Fischbach, M.A.

    2015-01-01

    Starting with the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced

  20. Visualizing the process of knowledge discovery

    Science.gov (United States)

    Han, Jianchao; Cercone, Nick

    2000-10-01

    Most existing visualization systems stress either the original data visualization of the discovered knowledge visualization, such as decision tree, neural network, rules, etc., but lack the abilities to visualize the entire process of knowledge discovery. We propose an interactive model, RuleViz, for visualizing the process of knowledge discovery and data mining. The RuleViz model consists of five components, each of which can be interacted and visualized by using different visualization techniques. According to this model, two interactive systems, AViz and CViz, for visualizing the process of discovering numerical association rules and the process of learning classification rules have been implemented, respectively. To preprocess the data, each system provides users with three approaches for discretizing numerical attributes and the corresponding rule discovery algorithms. The discretization approaches and the algorithms for discovering association rules and learning classification rules are presented, and the approaches to visualizing discretized data and discovered rules are developed. The discovery of numerical association rules in AViz is based on image-based mining algorithm, while, in CViz, the classification rules are learned in terms of a logical rule induction algorithm. We also demonstrate our experimental results with AViz and CViz on the census data sets, UCl data sets, and artificial data sets.

  1. The discovery and development of antiretroviral agents

    NARCIS (Netherlands)

    Lange, Joep M. A.; Ananworanich, Jintanat

    2014-01-01

    Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral

  2. 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 Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE...) Supplementation of response. A party who knows or later learns that a response is incorrect is under a duty to...

  3. The Discovery of the Double Helix

    CERN Multimedia

    CERN. Geneva

    2011-01-01

    Professor James D. Watson has kindly agreed to make a presentation on the 1953 finding of the Double Helix at the Cavendish Laboratory by Francis Crick and himself. Being one of the greatest scientific discoveries in human history, little else needs to be added.

  4. Cognitive Neuroscience Discoveries and Educational Practices

    Science.gov (United States)

    Sylwester, Robert

    2006-01-01

    In this article, the author describes seven movement-related areas of cognitive neuroscience research that will play key roles in shifting the current behavioral orientation of teaching and learning to an orientation that also incorporates cognitive neuroscience discoveries. These areas of brain research include: (1) mirroring system; (2) plastic…

  5. Translating Genomic Discoveries to Cure Ultrahypermutant ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Translating Genomic Discoveries to Cure Ultrahypermutant Mismatch Repair Deficient Brain Tumours. Malignant brain tumours are the most common cause of death among children with cancer, but there is no known cure. This project will advance research in this important field. Inherited mutations and childhood cancer.

  6. (Self-) Discovery Service: Helping Students Help Themselves

    Science.gov (United States)

    Debonis, Rocco; O'Donnell, Edward; Thomes, Cynthia

    2012-01-01

    EBSCO Discovery Service (EDS) has been heavily used by UMUC students since its implementation in fall 2011, but experience has shown that it is not always the most appropriate source for satisfying students' information needs and that they often need assistance in understanding how the tool works and how to use it effectively. UMUC librarians have…

  7. Microscopy Opening Up New Cancer Discovery Avenues

    Science.gov (United States)

    Today’s high-powered microscopes are allowing researchers to study the fine details of individual cells and to peer into cells, opening up new avenues of discovery about the inner workings of cells, including the events that can cause healthy cells to tra

  8. Rough – Granular Computing knowledge discovery models

    Directory of Open Access Journals (Sweden)

    Mohammed M. Eissa

    2016-11-01

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

  9. Social Relationship Discovery Via Call Records

    Directory of Open Access Journals (Sweden)

    Zhao Wen-Zhe

    2017-01-01

    Full Text Available Telecom users constitute a huge, but relatively sparse social network. Community discovery has been a research topic of data mining. Traditional algorithms are greatly influenced by outliers. This paper presents a new algorithm based on social triangle theory. Experiments show that the new algorithm is effective.

  10. Communication in Drug Development: "Translating" Scientific Discovery.

    Science.gov (United States)

    Settleman, Jeff; Cohen, Robert L

    2016-03-10

    The discovery and development of new medicines that promote human health and potentially extend natural life remains a remarkably challenging endeavor. In this Commentary, we identify key elements of communication required to successfully translate promising biological findings to novel approved drug therapies and discuss the attendant challenges and opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 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...

  12. 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...

  13. Zavoisky and the Discovery of EPR

    Indian Academy of Sciences (India)

    IAS Admin

    The name of the Soviet physicist Evgenii Konstantinovich. Zavoisky (1907–1976) belongs to the history of science due to his discovery of a fundamental physical phenomenon – elec- tron paramagnetic resonance (EPR) and a series of brilliant works in nuclear physics, controlled thermonuclear fusion and physical ...

  14. Biological Awareness: Statements for Self-Discovery.

    Science.gov (United States)

    Edington, D.W.; Cunningham, Lee

    This guide to biological awareness through guided self-discovery is based on 51 single focus statements concerning the human body. For each statement there are explanations of the underlying physiological principles and suggested activities and discussion ideas to encourage understanding of the statement in terms of the human body's functions,…

  15. 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.

  16. 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 AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES.... Nothing contained in this section may be interpreted to require the creation of a document, except that...

  17. Conference Abstracts: Translational Science and Drug Discovery ...

    African Journals Online (AJOL)

    Abstracts prsented at the "Translational Science and Drug Discovery: Impact on Health, Wellness, Environment and Economics" conference, July 27-29th, 2015, at the Hennessy Park Hotel, Ebène Cybercity, Mauritius. The conference was hosted by the Society for Free radical Research Africa and the International ...

  18. Swedish Chemists and Discovery of the Elements

    Science.gov (United States)

    Thomsen, Volker

    1996-10-01

    All of the elements not already known from antiquity were discovered in Europe and North America. So which country ranks number one on the discovery list? The question occurred to me while leafing through reference 1 in search of thermodynamic data on silicon. Never having seen such a tabulation, I wondered if it might prove useful in teaching. The question has a sports-related flavor that will appeal to many students. Personally, I picked England or Germany for #1. The actual result is surprising. The ranking considering only up to atomic number 103 is as follows: Note: Where two or more independent discoveries have been made, each country is credited. In the "others" category Austria and Denmark each has two discoveries. The remaining countries, with one each, are Finland, Italy, Mexico, Poland, Romania, Russia, and Spain. The high place for the USA is primarily due to the work done at Berkeley and Los Alamos on the transuranics. Without these discoveries, the US would have tied with Switzerland at three elements. Perhaps the most interesting aspect of this tabulation is that Swedish chemists have discovered the most elements. Four chemists alone account for twelve of the 20 discoveries: Baron Jöns Jakob Berzelius (1779-1848) is credited with four elements. His pupil, friend, and assistant, Carl Gustav Mosander (1797-1858) discovered three. P. T. Cleve also found three elements and Karl Wilhelm Scheele (1742-1786) discovered two. Biographical research on the Swedish chemists is a suitable assignment at the introductory level. Reasons for the predominance of Swedish chemists presents a challenging student research topic in the history of chemistry. Another interesting question at the introductory level is, transuranics aside, who discovered the most elements? At the more advanced level the question becomes, why? Literature Cited: 1. Emsley, J. The Elements; Clarendon: Oxford, 1989.

  19. Discovery in a World of Mashups

    Science.gov (United States)

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

    2014-12-01

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

  20. 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.

  1. 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).

  2. Space Shuttle Discovery arrives at Launch Pad 39A

    Science.gov (United States)

    2001-01-01

    KENNEDY SPACE CENTER, Fla. -- Space Shuttle Discovery arrives at Launch Pad 39A after an early morning rollout from the Vehicle Assembly Building. Discovery is scheduled to launch Aug. 3 on mission STS-105.

  3. Natural circulation cooldown analysis for Yonggwang 3 and 4 per US NRC BTP RSB 5-1 requirements

    International Nuclear Information System (INIS)

    Seo, J.T.; Ko, C.S.; Ro, T.S.; Simoni, L.P.

    2004-01-01

    The Natural Circulation Cooldown (NCC) analysis from normal operations to shutdown cooling entry conditions for Yonggwang units 3 and 4 (YGN 3 and 4) was performed within the requirements of U.S. Nuclear Regulatory Commission (NRC) Branch Technical Position (BTP) RSB 5-1. The results showed that the YGN 3 and 4 can be cooled and depressurized to the shutdown entry conditions (350 deg F, 410 psia) within 16 hours under natural circulation condition requiring only 78% of the minimum condensate water storage capacity in conformance with BTP RSB 5-1 requirements. The results also demonstrated that the safety grade Reactor Coolant Gas Vent System (RCGVS) has sufficient capacity for the RCS depressurization as well as for the steam void control in the reactor vessel upper head region. (author)

  4. Antileukemic ancistrobenomine B and related 5,1'-coupled naphthylisoquinoline alkaloids from the Chinese liana Ancistrocladus tectorius.

    Science.gov (United States)

    Bringmann, Gerhard; Seupel, Raina; Feineis, Doris; Xu, Minjuan; Zhang, Guoliang; Kaiser, Marcel; Brun, Reto; Seo, Ean-Jeong; Efferth, Thomas

    2017-09-01

    A striking feature of the metabolite pattern of the Southeast Asian liana Ancistrocladus tectorius (Ancistrocladaceae) is the predominance of 5,1'-coupled naphthylisoquinoline alkaloids. About 20 alkaloids of this coupling type have so far been discovered in this plant species. Here, we report on the isolation of four new 5,1'-linked naphthylisoquinolines from the twigs and stems of A. tectorius. Two of them, the ancistrobenomines B (5) and C (6), belong to the very rare group of alkaloids with a fully dehydrogenated isoquinoline portion. Likewise unusual for naphthylisoquinoline alkaloids is the presence of a hydroxymethylene group at C-3. Within the large class of meanwhile ca. 180 such natural products, this structural peculiarity had so far been known only from two other representatives isolated from the Malaysian species A. benomensis, and from one single naphthalene-devoid 3-hydroxymethyleneisoquinoline from A. tectorius. Seven further 5,1'-linked alkaloids, previously isolated from related Asian and African Ancistrocladus species, have now been identified for the first time in A. tectorius. Their structural elucidation was achieved by spectroscopic analysis including HRESIMS, 1D and 2D NMR, and by chemical (oxidative degradation) and chiroptical (electronic circular dichroism) methods. Ancistrobenomine B (5) exhibited moderate effects against Plasmodium falciparum and Trypanosoma brucei rhodesiense in vitro, and it was found to display strong cytotoxic activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Do giant oilfield discoveries fuel internal armed conflicts?

    OpenAIRE

    Yu-Hsiang Lei; Guy Michaels

    2011-01-01

    We use new data to examine the effects of giant oilfield discoveries around the world since 1946. On average, these discoveries increase per capita oil production and oil exports by up to 50 percent. But these giant oilfield discoveries also have a dark side: they increase the incidence of internal armed conflict by about 5-8 percentage points. This increased incidence of conflict due to giant oilfield discoveries is especially high for countries that had already experienced armed conflicts o...

  6. Boesenbergia rotunda: From Ethnomedicine to Drug Discovery

    Directory of Open Access Journals (Sweden)

    Tan Eng-Chong

    2012-01-01

    Full Text Available Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.

  7. Mass Spectrometry-Based Biomarker Discovery.

    Science.gov (United States)

    Zhou, Weidong; Petricoin, Emanuel F; Longo, Caterina

    2017-01-01

    The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

  8. Discovery and Selection of Semantic Web Services

    CERN Document Server

    Wang, Xia

    2013-01-01

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

  9. Golden Jubilee photos: A gargantuan discovery

    CERN Multimedia

    2004-01-01

    In July 1973, a groundbreaking discovery was announced in CERN's Main Auditorium: the Gargamelle group had found proof of the weak neutral current. The discovery confirmed the electroweak theory, which had predicted that the weak force and the electromagnetic force were different facets of the same interaction. This paved the way for the Grand Unified Theory, which holds that just after the birth of the Universe all forces were actually the same... Gargamelle, whose "body" now reposes in the Microcosm garden, was a huge bubble chamber weighing around 1000 tonnes, filled with 18 tonnes of liquid freon. Its size, worthy of the giant Gargantua - the son of Gargamelle - was mighty enough to catch neutrinos, the elusive neutral particles which career through space without leaving any tracks. In the photograph, an unseen neutrino interacts with an electron and emerges as a neutrino instead of changing into a muon - what is seen (vertically) is the track of the electron. This lepton event offers p...

  10. Panorama 2014 - New oil and gas discoveries

    International Nuclear Information System (INIS)

    Vially, Roland; Hureau, Geoffroy

    2013-12-01

    Spending on exploration increased significantly in 2012, and this growth should continue into 2013. Over a period of ten years, exploration budgets have increased five-fold, leading to major discoveries in regions as yet unexplored. In 2012, 25 billion barrels of oil equivalent (Gboe) were revealed. This is more than the average for the whole decade, but less than the amount for the previous year. Although knowledge of the volumes that have been discovered is still very fragmented, they should continue to fall into 2013. The main reason lies in the fact that spending on exploration is being shifted towards assessing discoveries made in previous years in the particularly prolific basins of Brazil and East Africa, while the exploration of border regions - such as the West African pre-salt formation - is still only in its early stages. (authors)

  11. Biopharmaceutical discovery and production in yeast.

    Science.gov (United States)

    Meehl, Michael A; Stadheim, Terrance A

    2014-12-01

    The selection of an expression platform for recombinant biopharmaceuticals is often centered upon suitable product titers and critical quality attributes, including post-translational modifications. Although notable differences between microbial, yeast, plant, and mammalian host systems exist, recent advances have greatly mitigated any inherent liabilities of yeasts. Yeast expression platforms are important to both the supply of marketed biopharmaceuticals and the pipelines of novel therapeutics. In this review, recent advances in yeast-based expression of biopharmaceuticals will be discussed. The advantages of using glycoengineered yeast as a production host and in the discovery space will be illustrated. These advancements, in turn, are transforming yeast platforms from simple production systems to key technological assets in the discovery and selection of biopharmaceutical lead candidates. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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.

  14. Accelerating the Rate of Astronomical Discovery

    Science.gov (United States)

    Norris, Ray P. Ruggles, Clive L. N.

    2010-05-01

    Special Session 5 on Accelerating the Rate of Astronomical Discovery addressed a range of potential limits to progress - paradigmatic, technological, organisational, and political - examining each issue both from modern and historical perspectives, and drawing lessons to guide future progress. A number of issues were identified which potentially regulate the flow of discoveries, such as the balance between large strongly-focussed projects and instruments, designed to answer the most fundamental questions confronting us, and the need to maintain a creative environment with room for unorthodox thinkers and bold, high risk, projects. Also important is the need to maintain historical and cultural perspectives, and the need to engage the minds of the most brilliant young people on the planet, regardless of their background, ethnicity, gender, or geography.

  15. Graph-Based Methods for Discovery Browsing with Semantic Predications

    DEFF Research Database (Denmark)

    Wilkowski, Bartlomiej; Fiszman, Marcelo; Miller, Christopher M

    2011-01-01

    We present an extension to literature-based discovery that goes beyond making discoveries to a principled way of navigating through selected aspects of some biomedical domain. The method is a type of "discovery browsing" that guides the user through the research literature on a specified phenomen...

  16. 49 CFR 1313.10 - Procedures for complaints and discovery.

    Science.gov (United States)

    2010-10-01

    ...) Discovery petition. A discovery petition must note on the front page “Petition for Discovery of Rail... perform its common carrier obligation, the nexus between the information sought and the common carrier.... Immediately upon the filing of a complaint, the rail carrier filing the contract summary shall forward to the...

  17. Parasites and infectious disease: discovery by serendipity, and otherwise

    National Research Council Canada - National Science Library

    Esch, Gerald W

    2007-01-01

    ... in generating breakthrough scientific discoveries, ranging from immunology to ecology, and from malaria and trypanosomiasis to schistosomiasis and Lyme disease. Some of these discoveries were made serendipitously and others only after relentless effort pointed to a specific solution. This engaging and lively introduction to discovery in parasit...

  18. 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

  19. An extended dual search space model of scientific discovery learning

    NARCIS (Netherlands)

    van Joolingen, Wouter; de Jong, Anthonius J.M.

    1997-01-01

    This article describes a theory of scientific discovery learning which is an extension of Klahr and Dunbar''s model of Scientific Discovery as Dual Search (SDDS) model. We present a model capable of describing and understanding scientific discovery learning in complex domains in terms of the SDDS

  20. The Neutron's Discovery - 80 Years on

    Science.gov (United States)

    Rogers, John D.

    A brief review is given of selected highlights in scientific developments from the birth of modern nuclear physics at the end of the 19th century to the discovery of the neutron in 1932. This is followed by some important milestones in neutron and reactor physics that have led to our current understanding and implementation of nuclear technologies. The beginnings can be traced back to the discovery of X-rays by Roentgen, the identification of natural radioactivity by Becquerel and the discovery of the electron by Thomson, towards the end of the 19th Century. Rutherford was a key figure in experimental physics who determined the structure of the atom and who inspired his students at McGill, Manchester and Cambridge Universities (many of whom would become Nobel laureates) in the pursuit of their physics research. One of Rutherford's students, James Chadwick, had studied the work carried out by Bothe and Becker on alpha particle-induced disintegration of light elements which had led to their observation of high energy penetrating radiation that neither they nor the Joliot-Curies could identify. Chadwick knew that the only possible explanation was the emission of a neutron in the nuclear reaction. He carried out tests in the Cavendish Laboratory and submitted his now classical paper identifying the neutron to the periodical Nature in 1932. The discovery of the neutron and of nuclear fission in 1939 opened up new areas for scientific investigation, in, for example, astrophysics, geology, neutron and nuclear physics. The prospects for nuclear power in particular appeared to be unlimited and both civil and military applications have been actively pursued. Many new experimental facilities have been designed and built to provide intense sources of neutrons for research purposes. Work carried out in such centres is included in the programme of the 7th International Topical Meeting on Neutron Radiography, an important forum for discussion of the latest research work of this

  1. Computational functional group mapping for drug discovery

    OpenAIRE

    Guvench, Olgun

    2016-01-01

    Computational functional group mapping (cFGM) is emerging as a high-impact complement to existing widely used experimental and computational structure-based drug discovery methods. cFGM provides comprehensive atomic-resolution 3D maps of the affinity of functional groups that can constitute drug-like molecules for a given target, typically a protein. These 3D maps can be intuitively and interactively visualized by medicinal chemists to rapidly design synthetically accessible ligands. Given th...

  2. From Discovery to Impact - Near Earth Asteroids

    Directory of Open Access Journals (Sweden)

    Miloš Tichý

    2012-10-01

    Full Text Available The Near-Earth Objects (NEOs are the most important of the small bodies of the solar system, having the capability of close approaches to the Earth and the chance to collide with the Earth.  We present here the current system of discovery of these dangerous objects, standards for selecting useful and important targets for NEO follow-up astrometry, system of impact probabilities calculations, and also determination of impact site and evacuation area.

  3. Photovoltaic Technology and Applications | Othieno | Discovery and ...

    African Journals Online (AJOL)

    La technologie photovoltaïque est donc passée en revue et des recommandations sont faites sur leur application pour l'électrification rurale dans les pays en voie de développement. Mots clés: énergie solaire, matériaux photovoltaïques, électrification rurale, énergie, coût, application (Discovery and innovation: 14(1-2): ...

  4. The Discovery of the Top Quark

    Science.gov (United States)

    Sinervo, P.K.

    1995-12-01

    The top quark and the Higgs boson are the heaviest elementary particles predicted by the standard model. The four lightest quark flavours, the up, down, strange and charm quarks, were well-established by the mid-1970's. The discovery in 1977 of the {Tau} resonances, a new family of massive hadrons, required the introduction of the fifth quark flavour. Experimental and theoretical studies have indicated that this quark also has a heavier partner, the top quark.

  5. Bioenergy Knowledge Discovery Framework Fact Sheet

    Energy Technology Data Exchange (ETDEWEB)

    None

    2017-07-01

    The Bioenergy Knowledge Discovery Framework (KDF) supports the development of a sustainable bioenergy industry by providing access to a variety of data sets, publications, and collaboration and mapping tools that support bioenergy research, analysis, and decision making. In the KDF, users can search for information, contribute data, and use the tools and map interface to synthesize, analyze, and visualize information in a spatially integrated manner.

  6. Discovery Monday - Behind the plug: communication networks

    CERN Multimedia

    2004-01-01

    Ever wondered what happens to your email when you click "send"? And when you make a phone call, how does your voice travel down the wire? Find out more about communication networks and their applications. Do not miss the next Discovery Monday in Microcosm on 1st March (see Bulletin 9/2004)! Monday 1st March from 7.30pm to 9.00pm, in Microcosm. Entrance Free.

  7. Discovery and Development of Calcium Channel Blockers

    OpenAIRE

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovere...

  8. Recent archaeological discoveries in East Kalimantan, Indonesia

    OpenAIRE

    Chazine, Jean-Michel; Ferrie, Jean-Georges

    2008-01-01

    International audience; Since 1992, thanks to the exceptional interest generated by caving teams crossing Kalimantan from west to east in 1988, a large quantity of archaeological discoveries has been revealed. A Franco-Indonesian team has surveyed caves and rockshelters in East Kalimantan to shed some light on an archaeologically unknown territory. Altogether, more than 100 caves have been visited and checked, of which over 30 contain undoubtable rock paintings. These sites are located in two...

  9. Important discoveries from analysing bacterial phenotypes

    OpenAIRE

    Bochner, Barry R; Giovannetti, Luciana; Viti, Carlo

    2008-01-01

    The ability to test hundreds to thousands of cellular phenotypes in a single experiment has opened up new avenues of investigation and exploration and led to important discoveries in very diverse applications of microbiological research and development. The information provided by global phenotyping is complementary to, and often more easily interpretable than information provided by global molecular analytical methods such as gene chips and proteomics. This report summarizes advances present...

  10. Systems Pharmacology in Small Molecular Drug Discovery.

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-02-18

    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.

  11. Discovery and History of Amino Acid Fermentation.

    Science.gov (United States)

    Hashimoto, Shin-Ichi

    There has been a strong demand in Japan and East Asia for L-glutamic acid as a seasoning since monosodium glutamate was found to present umami taste in 1907. The discovery of glutamate fermentation by Corynebacterium glutamicum in 1956 enabled abundant and low-cost production of the amino acid, creating a large market. The discovery also prompted researchers to develop fermentative production processes for other L-amino acids, such as lysine. Currently, the amino acid fermentation industry is so huge that more than 5 million metric tons of amino acids are manufactured annually all over the world, and this number continues to grow. Research on amino acid fermentation fostered the notion and skills of metabolic engineering which has been applied for the production of other compounds from renewable resources. The discovery of glutamate fermentation has had revolutionary impacts on both the industry and science. In this chapter, the history and development of glutamate fermentation, including the very early stage of fermentation of other amino acids, are reviewed.

  12. The Challenges of Interoperable Data Discovery

    Science.gov (United States)

    Meaux, Melanie F.

    2005-01-01

    The Global Change Master Directory (GCMD) assists the oceanographic community in data discovery and access through its online metadata directory. The directory also offers data holders a means to post and search their oceanographic data through the GCMD portals, i.e. online customized subset metadata directories. The Gulf of Maine Ocean Data Partnership (GoMODP) has expressed interest in using the GCMD portals to increase the visibility of their data holding throughout the Gulf of Maine region and beyond. The purpose of the Gulf of Maine Ocean Data Partnership (GoMODP) is to "promote and coordinate the sharing, linking, electronic dissemination, and use of data on the Gulf of Maine region". The participants have decided that a "coordinated effort is needed to enable users throughout the Gulf of Maine region and beyond to discover and put to use the vast and growing quantities of data in their respective databases". GoMODP members have invited the GCMD to discuss further collaborations in view of this effort. This presentation. will focus on the GCMD GoMODP Portal - demonstrating its content and use for data discovery, and will discuss the challenges of interoperable data discovery. interoperability among metadata standards and vocabularies will be discussed. A short overview of the lessons learned at the Marine Metadata Interoperability (MMI) metadata workshop held in Boulder, Colorado on August 9-11, 2005 will be given.

  13. Pathways to new drug discovery in neuropsychiatry.

    Science.gov (United States)

    Berk, Michael

    2012-11-29

    There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents. Serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option, as is illustrated by the suggestion in the paper by Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk of affective disorder. However, the identification of agents targeting disorder-related biomarkers is currently proving particularly fruitful. There is considerable hope for genetics as a purist, pathophysiologically valid pathway to drug discovery; however, it is unclear whether the science is ready to meet this promise. Fruitful paradigms will require a break from the orthodoxy, and creativity and risk may well be the fingerprints of success.See related article http://www.biomedcentral.com/1741-7015/10/150.

  14. 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.

  15. 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.

  16. Pathways to new drug discovery in neuropsychiatry

    Directory of Open Access Journals (Sweden)

    Berk Michael

    2012-11-01

    Full Text Available Abstract There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents. Serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option, as is illustrated by the suggestion in the paper by Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk of affective disorder. However, the identification of agents targeting disorder-related biomarkers is currently proving particularly fruitful. There is considerable hope for genetics as a purist, pathophysiologically valid pathway to drug discovery; however, it is unclear whether the science is ready to meet this promise. Fruitful paradigms will require a break from the orthodoxy, and creativity and risk may well be the fingerprints of success. See related article http://www.biomedcentral.com/1741-7015/10/150

  17. Performance Evaluation of Frequent Subgraph Discovery Techniques

    Directory of Open Access Journals (Sweden)

    Saif Ur Rehman

    2014-01-01

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

  18. Molecular dynamics simulations and novel drug discovery.

    Science.gov (United States)

    Liu, Xuewei; Shi, Danfeng; Zhou, Shuangyan; Liu, Hongli; Liu, Huanxiang; Yao, Xiaojun

    2018-01-01

    Molecular dynamics (MD) simulations can provide not only plentiful dynamical structural information on biomacromolecules but also a wealth of energetic information about protein and ligand interactions. Such information is very important to understanding the structure-function relationship of the target and the essence of protein-ligand interactions and to guiding the drug discovery and design process. Thus, MD simulations have been applied widely and successfully in each step of modern drug discovery. Areas covered: In this review, the authors review the applications of MD simulations in novel drug discovery, including the pathogenic mechanisms of amyloidosis diseases, virtual screening and the interaction mechanisms between drugs and targets. Expert opinion: MD simulations have been used widely in investigating the pathogenic mechanisms of diseases caused by protein misfolding, in virtual screening, and in investigating drug resistance mechanisms caused by mutations of the target. These issues are very difficult to solve by experimental methods alone. Thus, in the future, MD simulations will have wider application with the further improvement of computational capacity and the development of better sampling methods and more accurate force fields together with more efficient analysis methods.

  19. Workshop on Discovery Lessons-Learned

    Science.gov (United States)

    Saunders, M. (Editor)

    1995-01-01

    As part of the Discovery Program's continuous improvement effort, a Discovery Program Lessons-Learned workshop was designed to review how well the Discovery Program is moving toward its goal of providing low-cost research opportunities to the planetary science community while ensuring continued U.S. leadership in solar system exploration. The principal focus of the workshop was on the recently completed Announcement of Opportunity (AO) cycle, but the program direction and program management were also open to comment. The objective of the workshop was to identify both the strengths and weaknesses of the process up to this point, with the goal of improving the process for the next AO cycle. The process for initializing the workshop was to solicit comments from the communities involved in the program and to use the feedback as the basis for establishing the workshop agenda. The following four sessions were developed after reviewing and synthesizing both the formal feedback received and informal feedback obtained during discussions with various participants: (1) Science and Return on Investment; (2) Technology vs. Risk; Mission Success and Other Factors; (3) Cost; and (4) AO.AO Process Changes and Program Management.

  20. Towards Robot Scientists for autonomous scientific discovery.

    Science.gov (United States)

    Sparkes, Andrew; Aubrey, Wayne; Byrne, Emma; Clare, Amanda; Khan, Muhammed N; Liakata, Maria; Markham, Magdalena; Rowland, Jem; Soldatova, Larisa N; Whelan, Kenneth E; Young, Michael; King, Ross D

    2010-01-04

    We review the main components of autonomous scientific discovery, and how they lead to the concept of a Robot Scientist. This is a system which uses techniques from artificial intelligence to automate all aspects of the scientific discovery process: it generates hypotheses from a computer model of the domain, designs experiments to test these hypotheses, runs the physical experiments using robotic systems, analyses and interprets the resulting data, and repeats the cycle. We describe our two prototype Robot Scientists: Adam and Eve. Adam has recently proven the potential of such systems by identifying twelve genes responsible for catalysing specific reactions in the metabolic pathways of the yeast Saccharomyces cerevisiae. This work has been formally recorded in great detail using logic. We argue that the reporting of science needs to become fully formalised and that Robot Scientists can help achieve this. This will make scientific information more reproducible and reusable, and promote the integration of computers in scientific reasoning. We believe the greater automation of both the physical and intellectual aspects of scientific investigations to be essential to the future of science. Greater automation improves the accuracy and reliability of experiments, increases the pace of discovery and, in common with conventional laboratory automation, removes tedious and repetitive tasks from the human scientist.

  1. Two kinds of knowledge in scientific discovery.

    Science.gov (United States)

    Bridewell, Will; Langley, Pat

    2010-01-01

    Research on computational models of scientific discovery investigates both the induction of descriptive laws and the construction of explanatory models. Although the work in law discovery centers on knowledge-lean approaches to searching a problem space, research on deeper modeling tasks emphasizes the pivotal role of domain knowledge. As an example, our own research on inductive process modeling uses information about candidate processes to explain why variables change over time. However, our experience with IPM, an artificial intelligence system that implements this approach, suggests that process knowledge is insufficient to avoid consideration of implausible models. To this end, the discovery system needs additional knowledge that constrains the model structures. We report on an extended system, SC-IPM, that uses such information to reduce its search through the space of candidates and to produce models that human scientists find more plausible. We also argue that although people carry out less extensive search than SC-IPM, they rely on the same forms of knowledge--processes and constraints--when constructing explanatory models. Copyright © 2009 Cognitive Science Society, Inc.

  2. Integrated system for safe transportation of children to school. HMI concepts. Deliverable D5.1. WP5 User interface design and development. Activity A5.1. User interface design and overall information and warning concept

    OpenAIRE

    DIEDERICHS, F; PAUZIE, A; VESTLIN, S; WERNER, J; SPENCE, A; PORATHE, T; KALORIGOU, K; EGGER, S

    2011-01-01

    The purpose of Deliverable 5.1 is to describe the general Human Machine Interaction (HMI) concept of SAFEWAY2SCHOOL. The concept is composed of a set of HMI devices with interfaces to the different users of the system. It defines the product idea, use cases, user needs and high level objectives for each device. In order to achieve an accepted and usable HMI for all SAFEWAY2SCHOOL devices and interfaces the deliverable provides generic HMI guidelines and requirements for HMI design that can be...

  3. 26 CFR 301.6103(j)(5)-1 - Disclosures of return information reflected on returns to officers and employees of the...

    Science.gov (United States)

    2010-04-01

    ... agriculture. 301.6103(j)(5)-1 Section 301.6103(j)(5)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... Returns Returns and Records § 301.6103(j)(5)-1 Disclosures of return information reflected on returns to...) General rule. Pursuant to the provisions of section 6103(j)(5) of the Internal Revenue Code and subject to...

  4. Meeting report on the Alzheimer?s Drug Discovery Foundation 14th International Conference on Alzheimer?s Drug Discovery

    OpenAIRE

    Friedman, Lauren G; Price, Katherine; Lane, Rachel F; Carman, Aaron J; Dacks, Penny A; Shineman, Diana W; Fillit, Howard M

    2014-01-01

    The Alzheimer?s Drug Discovery Foundation?s 14th International Conference on Alzheimer?s Drug Discovery was held on 9 and 10 September in Jersey City, NJ, USA. This annual meeting highlights novel therapeutic approaches supported by the Alzheimer?s Drug Discovery Foundation in development for Alzheimer?s disease and related dementias.

  5. 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.

  6. Hoe akkuraat kan ’n Bybelvertaling wees? [vreemd taal weggelaat] in 1 Johannes 5:1-4 as voorbeeld

    Directory of Open Access Journals (Sweden)

    Jan van der Watt

    2004-12-01

    An analysis is made of different translations of [foreign font omitted] in 1 John 5:1-4. The inconsistencies in and among translations are noted. The influence of the socio-cultural ecology as well as the literary and grammatical aspects that play a role in the process of translation, are then illustrated. The complex nature of translation is underlined and it is suggested that the focus should fall on the purpose of a particular translation. This will lead to the purposeful use of different translating techniques in any particular translation. [We apologise for the poor quality of the foreign font

  7. Synthesis, Characterization and Antimicrobial Activity of Metal Chelates of 5-[1(H-Benzotriazole methylene]-8-quinolinol

    Directory of Open Access Journals (Sweden)

    H. S. Patel

    2009-01-01

    Full Text Available 5-Chloromethyl-8-quinolinol was condensed stoichiometrically with benzotriazole in presence of potassium carbonate. The resulting 5-[1(H-benzo triazole methylene]-8-quinolinol (BTMQ was characterized by elemental analysis and spectral studies. The transition metal chelates viz. Cu2+, Ni2+, Co3+, Mn2+ and Zn2+ of BTMQ were prepared and characterized by metal-ligand (M:L ratio, IR and reflectance spectral studies and magnetic properties. The antifungal activity of BTMQ and its metal chelates was screened against various fungi. The results show that all these samples are good antifungal agents.

  8. 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. ...... 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.......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...

  9. Research and Development Toward a 4.5-1.5 Angstrom Linac Coherent Light Source (LCLS) at SLAC

    International Nuclear Information System (INIS)

    Tatchyn, R.; Arthur, J.; Baltay, M.

    1995-08-01

    In recent years significant studies have been initiated on the feasibility of utilizing a portion of the 3km S-band accelerator at SLAC to drive a short wavelength (4.5-1.5 A) Linac Coherent Light Source (LCLS), a Free Electron Laser (FEL) operating in the Self- Amplified Spontaneous Emission (SASE) regime. Electron beam requirements for single-pass saturation in a minimal time include: (1) a peak current in the 7 kA range, (2) a relative energy spread of <0.05%, and (3) a transverse emittance, ε[r-m], approximating the diffraction limit condition ε = λ / 4π, where lambda(m) is the output wavelength. Requirements on the insertion device include field error levels of 0.02% for keeping the electron bunch centered on and in phase with the amplified photons, and a focusing beta of 8 m/rad for inhibiting the dilution of its transverse density. Although much progress has been made in developing individual components and beam processing techniques necessary for LCLS operation down to approx. 20 A, a substantial amount of research and development is still required in a number of theoretical and experimental areas leading to the construction and operation of a 4.5-1.5 A LCLS. In this paper we report on a research and development program underway and in planning at SLAC for addressing critical questions in these areas

  10. Practical system for recording spatially lifelike 5.1 surround sound and 3D fully periphonic reproduction

    Science.gov (United States)

    Miller, Robert E. (Robin)

    2005-04-01

    In acoustic spaces that are played as extensions of musical instruments, tonality is a major contributor to the experience of reality. Tonality is described as a process of integration in our consciousness over the reverberation time of the room of many sonic arrivals in three dimensions, each directionally coded in a learned response by the listeners unique head-related transfer function (HRTF). Preserving this complex 3D directionality is key to lifelike reproduction of a recording. Conventional techniques such as stereo or 5.1-channel surround sound position the listener at the apex of a triangle or the center of a circle, not the center of the sphere of lifelike hearing. A periphonic reproduction system for music and movie entertainment, Virtual Reality, and Training Simulation termed PerAmbio 3D/2D (Pat. pending) is described in theory and subjective tests that capture the 3D sound field with a microphone array and transform the periphonic signals into ordinary 6-channel media for either decoderless 2D replay on 5.1 systems, or lossless 3D replay with decoder and five additional speakers. PerAmbio 3D/2D is described as a practical approach to preserving the spatial perception of reality, where the listening room and speakers disappear, leaving the acoustical impression of the original venue.

  11. The future of crystallography in drug discovery.

    Science.gov (United States)

    Zheng, Heping; Hou, Jing; Zimmerman, Matthew D; Wlodawer, Alexander; Minor, Wladek

    2014-02-01

    X-ray crystallography plays an important role in structure-based drug design (SBDD), and accurate analysis of crystal structures of target macromolecules and macromolecule-ligand complexes is critical at all stages. However, whereas there has been significant progress in improving methods of structural biology, particularly in X-ray crystallography, corresponding progress in the development of computational methods (such as in silico high-throughput screening) is still on the horizon. Crystal structures can be overinterpreted and thus bias hypotheses and follow-up experiments. As in any experimental science, the models of macromolecular structures derived from X-ray diffraction data have their limitations, which need to be critically evaluated and well understood for structure-based drug discovery. This review describes how the validity, accuracy and precision of a protein or nucleic acid structure determined by X-ray crystallography can be evaluated from three different perspectives: i) the nature of the diffraction experiment; ii) the interpretation of an electron density map; and iii) the interpretation of the structural model in terms of function and mechanism. The strategies to optimally exploit a macromolecular structure are also discussed in the context of 'Big Data' analysis, biochemical experimental design and structure-based drug discovery. Although X-ray crystallography is one of the most detailed 'microscopes' available today for examining macromolecular structures, the authors would like to re-emphasize that such structures are only simplified models of the target macromolecules. The authors also wish to reinforce the idea that a structure should not be thought of as a set of precise coordinates but rather as a framework for generating hypotheses to be explored. Numerous biochemical and biophysical experiments, including new diffraction experiments, can and should be performed to verify or falsify these hypotheses. X-ray crystallography will find its

  12. Solar System Moons Discovery and Mythology

    CERN Document Server

    Blunck, Jürgen

    2010-01-01

    Starting from Mars outward this concise handbook provides thorough information on the satellites of the planets in the solar system. Each chapter begins with a section on the discovery and the naming of the planet's satellites or rings. This is followed by a section presenting the historic sources of those names. The book contains tables with the orbital and physical parameters of all satellites and is illustrated throughout with modern photos of the planets and their moons as well as historical and mythological drawings. The Cyrillic transcriptions of the satellite names are provided in a register. Readers interested in the history of astronomy and its mythological backgrounds will enjoy this beautiful volume.

  13. Studying Scientific Discovery by Computer Simulation.

    Science.gov (United States)

    1983-03-30

    MAR 83 UNCLASSIFIED CMU-CIP-WP-444 NOOOI4-82-K-0168 F/G 9/2 NL 4lU iQ 111125 . 1 MICROCOPY RESOLUIION TESI CHART NAL URLAD Of SIANDARDS %4 A Isp...About 1760 - the exact date is not known - Joseph Black, a Scottish chemistry professor, made the first of the several important discoveries that have...preserved his name.5 Using data reported in a standard chemistry textbook of his time (Boerhaave’s) and obtained from an experiment performed at

  14. The discovery of columnar jointing on Mars

    Science.gov (United States)

    Milazzo, M.P.; Keszthelyi, L.P.; Jaeger, W.L.; Rosiek, M.; Mattson, S.; Verba, C.; Beyer, R.A.; Geissler, P.E.; McEwen, A.S.; ,

    2009-01-01

    We report on the discovery of columnar jointing in Marte Valles, Mars. These columnar lavas were discovered in the wall of a pristine, 16-km-diameter impact crater and exhibit the features of terrestrial columnar basalts. There are discontinuous outcrops along the entire crater wall, suggesting that the columnar rocks covered a surface area of at least 200 km2, assuming that the rocks obliterated by the impact event were similarly jointed. We also see columns in the walls of other fresh craters in the nearby volcanic plains of Elysium Planitia–Amazonis Planitia, which include Marte Vallis, and in a well-preserved crater in northeast Hellas.

  15. Big Data for cardiology: novel discovery?

    Science.gov (United States)

    Mayer-Schönberger, Viktor

    2016-03-21

    Big Data promises to change cardiology through a massive increase in the data gathered and analysed; but its impact goes beyond improving incrementally existing methods. The potential of comprehensive data sets for scientific discovery is examined, and its impact on the scientific method generally and cardiology in particular is posited, together with likely consequences for research and practice. Big Data in cardiology changes how new insights are being discovered. For it to flourish, significant modifications in the methods, structures, and institutions of the profession are necessary. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  16. Motif discovery in ranked lists of sequences

    DEFF Research Database (Denmark)

    Nielsen, Morten Muhlig; Tataru, Paula; Madsen, Tobias

    2016-01-01

    a growing need for motif analysis methods that can exploit this coupled data structure and be tailored for specific biological questions. Here, we present an exploratory motif analysis tool, Regmex (REGular expression Motif EXplorer), which offers several methods to evaluate the correlation of motifs....... These features make Regmex well suited for a range of biological sequence analysis problems related to motif discovery, exemplified by microRNA seed enrichment, but also including enrichment problems involving complex motifs and combinations of motifs. We demonstrate a number of usage scenarios that take...

  17. Advances in knowledge discovery in databases

    CERN Document Server

    Adhikari, Animesh

    2015-01-01

    This book presents recent advances in Knowledge discovery in databases (KDD) with a focus on the areas of market basket database, time-stamped databases and multiple related databases. Various interesting and intelligent algorithms are reported on data mining tasks. A large number of association measures are presented, which play significant roles in decision support applications. This book presents, discusses and contrasts new developments in mining time-stamped data, time-based data analyses, the identification of temporal patterns, the mining of multiple related databases, as well as local patterns analysis.  

  18. Toward discovery science of human brain function

    DEFF Research Database (Denmark)

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints...... of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (... individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships...

  19. Discovery learning in math: Exercises versus problems

    Directory of Open Access Journals (Sweden)

    Barry Garelick

    2009-02-01

    Full Text Available In this article, Garelick confronts the myth perpetrated in education schools that math is incorrectly taught by teaching students to do "exercises" rather than solving "problems". The former are viewed as inauthentic experiences in which the student applies algorithms to previously learned types of problems in a mechanical type way. In fact, it is through the working of the so-called "exercises" that students can make meaningful discoveries which ultimately lead them to solving more complex problems. As it is, many of today's math programs have students reaching for the stars by standing on a two-legged stool.

  20. The discovery potential of laser polarization experiments

    International Nuclear Information System (INIS)

    Ahlers, Markus

    2008-12-01

    Currently, a number of experiments are searching for vacuum magnetic birefringence and dichroism, i.e. for dispersive and absorptive features in the propagation of polarized light along a transverse magnetic field in vacuum. In this note we calculate the Standard Model contributions to these signatures, thereby illuminating the discovery potential of such experiments in the search for new physics. We discuss the three main sources for a Standard Model contribution to a dichroism signal: photon splitting, neutrino pair production and production of gravitons. (orig.)

  1. The discovery potential of laser polarization experiments

    Energy Technology Data Exchange (ETDEWEB)

    Ahlers, Markus [Oxford Univ. (United Kingdom). Rudolf Peierls Centre for Theoretical Physics; Jaeckel, Joerg [Durham Univ. (United Kingdom). Inst. for Particle Physics and Phenomenology; Ringwald, Andreas [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2008-12-15

    Currently, a number of experiments are searching for vacuum magnetic birefringence and dichroism, i.e. for dispersive and absorptive features in the propagation of polarized light along a transverse magnetic field in vacuum. In this note we calculate the Standard Model contributions to these signatures, thereby illuminating the discovery potential of such experiments in the search for new physics. We discuss the three main sources for a Standard Model contribution to a dichroism signal: photon splitting, neutrino pair production and production of gravitons. (orig.)

  2. Discovery Mondays: Much ado about nothing: vacuums

    CERN Multimedia

    2004-01-01

    Most people seem to agree that an empty space has nothing in it. But what about the physicists? "Wait a minute!", they will tell you, at the Microcosm's next Discovery Monday on 5th April, for they know that even interstellar space is not as empty as it might seem... Come and discover the technological advances made at CERN and their everyday applications. Take a step into the world of the vacuum... The event will take place in the Microcosm on 5th April, from 7.30 p.m. to 9.00 p.m. Entrance is free.

  3. Discovery Monday - Behind the plug: communication networks

    CERN Multimedia

    2004-01-01

    Ever wondered what happens to your email when you click "send"? And when you make a phone call, how does your voice travel down the wire? Find out more about communication networks and their applications at the next Discovery Monday in Microcosm on 1 March. At CERN, networks are used for a multitude of reasons. Mobile phones, for example, are used in the laboratory's underground areas. Optical fibre cabling ensures that CERN's computers are connected to the rest of the world. But how do optical fibres work and what does the future have in store? CERN's experiments also need networks. Particle detectors are made of many layers, each relays complex information to a computer analysis centre which reconstitutes the passage of the particles resulting from collisions. Many billions of bytes are transmitted every second from a multitude of sources, to many computers.  No single computer can handle such a huge flow of information. The next Discovery Monday is your chance to find out how this works.  Participate i...

  4. New paradigms in GPCR drug discovery.

    Science.gov (United States)

    Jacobson, Kenneth A

    2015-12-15

    G protein-coupled receptors (GPCRs) remain a major domain of pharmaceutical discovery. The identification of GPCR lead compounds and their optimization are now structure-based, thanks to advances in X-ray crystallography, molecular modeling, protein engineering and biophysical techniques. In silico screening provides useful hit molecules. New pharmacological approaches to tuning the pleotropic action of GPCRs include: allosteric modulators, biased ligands, GPCR heterodimer-targeted compounds, manipulation of polypharmacology, receptor antibodies and tailoring of drug molecules to fit GPCR pharmacogenomics. Measurements of kinetics and drug efficacy are factors influencing clinical success. With the exception of inhibitors of GPCR kinases, targeting of intracellular GPCR signaling or receptor cycling for therapeutic purposes remains a futuristic concept. New assay approaches are more efficient and multidimensional: cell-based, label-free, fluorescence-based assays, and biosensors. Tailoring GPCR drugs to a patient's genetic background is now being considered. Chemoinformatic tools can predict ADME-tox properties. New imaging technology visualizes drug action in vivo. Thus, there is reason to be optimistic that new technology for GPCR ligand discovery will help reverse the current narrowing of the pharmaceutical pipeline. Published by Elsevier Inc.

  5. X-Ray Astronomy Discovery Experiments, III*

    Science.gov (United States)

    Fisher, P. C.

    2011-04-01

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

  6. Discovery Mondays - The detectors: tracking particles

    CERN Document Server

    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. Discovery Mondays - The detectors: tracking particles

    CERN Document Server

    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 and generate collisions between them at extraordinary energies. The collisions give birth to showers of new particles. What are they? In order to find out, physicists slip into the role of detectives thanks to the detectors. At the next Discovery Monday you will find out about the different methods used at CERN to detect particles. A cloud chamber will allow you to see the tracks of cosmic particles live. You will also be given the chance to see real modules for the ATLAS and for the LHCb experiments. Strange materials will be on hand, such as crystals that are heavier than iron and yet as transparent as glass... Come to the Microcosm and become a top detective yourself! This event will take place in French. Join us at the Microcosm (Reception Building 33, M...

  8. FastMotif: spectral sequence motif discovery.

    Science.gov (United States)

    Colombo, Nicoló; Vlassis, Nikos

    2015-08-15

    Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, most of the existing motif finding algorithms are computationally demanding, and they may not be able to support the increasingly large datasets produced by modern high-throughput sequencing technologies. We present FastMotif, a new motif discovery algorithm that is built on a recent machine learning technique referred to as Method of Moments. Based on spectral decompositions, our method is robust to model misspecifications and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. On HT-Selex data, FastMotif extracts motif profiles that match those computed by various state-of-the-art algorithms, but one order of magnitude faster. We provide a theoretical and numerical analysis of the algorithm's robustness and discuss its sensitivity with respect to the free parameters. The Matlab code of FastMotif is available from http://lcsb-portal.uni.lu/bioinformatics. vlassis@adobe.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. First discovery of Holocene cryptotephra in Amazonia.

    Science.gov (United States)

    Watson, Elizabeth J; Swindles, Graeme T; Savov, Ivan P; Bacon, Karen L

    2015-10-23

    The use of volcanic ash layers for dating and correlation (tephrochronology) is widely applied in the study of past environmental changes. We describe the first cryptotephra (non-visible volcanic ash horizon) to be identified in the Amazon basin, which is tentatively attributed to a source in the Ecuadorian Eastern Cordillera (0-1°S, 78-79°W), some 500-600 km away from our field site in the Peruvian Amazon. Our discovery 1) indicates that the Amazon basin has been subject to volcanic ash fallout during the recent past; 2) highlights the opportunities for using cryptotephras to date palaeoenvironmental records in the Amazon basin and 3) indicates that cryptotephra layers are preserved in a dynamic Amazonian peatland, suggesting that similar layers are likely to be present in other peat sequences that are important for palaeoenvironmental reconstruction. The discovery of cryptotephra in an Amazonian peatland provides a baseline for further investigation of Amazonian tephrochronology and the potential impacts of volcanism on vegetation.

  10. Centenary of the discovery of superconductivity

    CERN Multimedia

    Anaïs Vernède

    2011-01-01

    To mark the centenary of the discovery of the phenomenon of superconductivity, MANEP and the University of Geneva are organising open days at the PhysiScope between 8 and 15 April 2011. On 13 April CERN will make a contribution to the series of events with a lecture on superconductivity followed by a demonstration of the phenomenon at the Globe   Historic graph showing the superconducting transition of mercury, measured in Leiden in 1911 by H. Kamerlingh Onnes. On 8 April 2011 it will be a hundred years since the discovery of superconductivity by the Dutch physicist Kamerlingh Onnes. To mark the occasion, the University of Geneva and MANEP are organising a week-long interactive workshop at the PhysiScope. “The purpose of this initiative is to introduce the general public to this spectacular phenomenon by giving them an opportunity to take part in entertaining experiments”, explains Adriana Aleman, Head of Communications of the University of Geneva. As its contribution to the e...

  11. Novel drug discovery for Chagas disease.

    Science.gov (United States)

    Moraes, Carolina B; Franco, Caio H

    2016-01-01

    Chagas disease is a chronic infection associated with long-term morbidity. Increased funding and advocacy for drug discovery for neglected diseases have prompted the introduction of several important technological advances, and Chagas disease is among the neglected conditions that has mostly benefited from technological developments. A number of screening campaigns, and the development of new and improved in vitro and in vivo assays, has led to advances in the field of drug discovery. This review highlights the major advances in Chagas disease drug screening, and how these are being used not only to discover novel chemical entities and drug candidates, but also increase our knowledge about the disease and the parasite. Different methodologies used for compound screening and prioritization are discussed, as well as novel techniques for the investigation of these targets. The molecular mechanism of action is also discussed. Technological advances have been executed with scientific rigour for the development of new in vitro cell-based assays and in vivo animal models, to bring about novel and better drugs for Chagas disease, as well as to increase our understanding of what are the necessary properties for a compound to be successful in the clinic. The gained knowledge, combined with new exciting approaches toward target deconvolution, will help identifying new targets for Chagas disease chemotherapy in the future.

  12. Business Model Discovery by Technology Entrepreneurs

    Directory of Open Access Journals (Sweden)

    Steven Muegge

    2012-04-01

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

  13. New genetic discoveries and primary immune deficiencies.

    Science.gov (United States)

    Hernandez-Trujillo, Vivian

    2014-04-01

    The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

  14. Synthetic biology for pharmaceutical drug discovery

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2015-01-01

    Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. PMID:26673570

  15. Scientists Like Me: Faces of Discovery

    Science.gov (United States)

    Enevoldsen, A. A. G.; Culp, S.; Trinh, A.

    2010-08-01

    During the International Year of Astronomy, Pacific Science Center is hosting a photography exhibit: Scientists Like Me: Faces of Discovery. The exhibit contains photographs of real, current astronomers and scientists working in astronomy and aerospace-related fields from many races, genders, cultural affiliations and walks of life. The photographs were taken and posters designed by Alyssa Trinh and Sarah Culp, high school interns in Discovery Corps, Pacific Science Center's youth development program. The direct contact between the scientists and the interns helps the intended audience of teachers and families personally connect with scientists. The finished posters from this exhibit are available online (http://pacificsciencecenter.org/scientists) for teachers to use in their classrooms, in addition to being displayed at Pacific Science Center and becoming part of Pacific Science Center's permanent art rotation. The objective of this project was to fill a need for representative photographs of scientists in the world community. It also met two of the goals of International Year of Astronomy: to provide a modern image of science and scientists, and to improve the gender-balanced representation of scientists at all levels and promote greater involvement by all people in scientific and engineering careers. We would like to build on the success of this project and create an annual summer internship, with different interns, focusing on creating posters for different fields of science.

  16. Feedback-Driven Dynamic Invariant Discovery

    Science.gov (United States)

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

    2014-01-01

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

  17. Discovery potential for supersymmetry in CMS

    CERN Document Server

    Abdullin, Salavat; Charles, François; Denegri, Daniel; Dydak, U; Dzelalija, Mile; Genchev, Vladimir; Graham, Douglas Jonathon; Iashvili, Ia; Kharchilava, Avto; Kinnunen, Ritva; Kunori, Shuichi; Mazumdar, Kajari; Racca, Chantal; Rurua, Lali; Stepanov, Nikita; Womersley, J

    2002-01-01

    This work summarizes and puts in an overall perspective studies done within CMS concerning the discovery potential for squarks and gluinos, sleptons, charginos and neutralinos, SUSY dark matter, lightest Higgs, sparticle mass determination methods and the detector design optimisation in view of SUSY searches. It represents the status of our understanding of these subjects as of Summer 1997. As a benchmark model we used the minimal supergravity-inspired super- symmetric standard model (mSUGRA) with a stable LSP. Discovery of SUSY at the LHC should be relatively straightforward. It may occur through the observation of a large excesses of events in missing E_T + jets, or with one or more isolated leptons. An excess of trilepton events or of isolated dileptons with E_T^miss, exhibiting a characteristic signature in the l^+l^- invariant mass distribution could also be the first manifestation of SUSY production. Squark and gluino production may represent a copious source of Higgs bosons through cascade decays. The ...

  18. Discovery Mondays: crystals and particles for medicine

    CERN Document Server

    2003-01-01

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

  19. Optical design of the Discovery Channel Telescope

    Science.gov (United States)

    MacFarlane, Malcolm J.; Dunham, Edward W.

    2004-10-01

    The Discovery Channel Telescope (DCT) is a joint venture between Discovery Communications and Lowell Observatory. The telescope will have a 4.2-meter clear aperture, active primary mirror working at F/1.9. Two observing stations are presently planned; a Ritchey-Chretien focus some two meters behind the vertex of the primary mirror and a prime focus featuring a wide-field optical corrector (WFOC) with a two-degree field of view. The Ritchey-Chretien focus will be used for a variety of optical and near infrared imaging and spectroscopic instrumentation while the prime focus will be largely used as a survey tool to search for near-earth and Kuiper belt objects, for example. In order to take advantage of sub-arc second seeing at the DCT site, a stringent set of requirements has been placed on the two foci. The requirements are for the full-width, half-maximum (FWHM) image of a point source to be less than 0.20 arc second at the Ritchey-Chretien focus over a 21 arc minute field and less than 0.27 arc second at prime focus in each of six filter bands including a very broad band for survey purposes. This paper describes the optical design of the field correctors at the two foci. Particular attention is paid to the WFOC. This state of the art device poses a number of optical challenges which are discussed here, as well as mechanical challenges which are discussed elsewhere.

  20. ANALISIS PERUBAHAN MASSA BAHAN FISIL DAN NON FISIL DALAM TERAS PWR 1000 MWe DENGAN ORIGEN-ARP 5.1

    Directory of Open Access Journals (Sweden)

    Anis Rohanda

    2015-03-01

    Full Text Available Teras reaktor merupakan tempat terjadinya reaksi pembelahan (fisi yang terkendali. Komponen reaktor seperti bahan bakar, kelongsong (cladding dan air pendingin memiliki peranan penting dalam keberlangsungan reaksi fisi. Reaksi fisi mengakibatkan terbentuknya sejumlah nuklida hasil fisi dan hasil aktivasi. Hasil fisi berasal dari reaksi tangkapan neutron termal dengan bahan fisil sedangkan hasil aktivasi berasal dari interaksi bahan non fisil seperti material kelongsong dan pendingin oleh neutron dan gamma. Pada setiap pengoperasian suatu reaktor, informasi perubahan massa bahan fisil dan non fisil sangat berguna untuk manajemen bahan bakar dalam teras, seperti pengaturan reaktivitas, optimasi dan pemuatan bahan bakar. Untuk itu perlu dilakukan penelitian mengenai perubahan bahan fisil dan non fisil tersebut dalam teras reaktor. Hal ini dapat dilakukan dengan mengamati perubahan massa dari material dalam teras reaktor. Penelitian ini memiliki tujuan untuk mengetahui perubahan massa unsur penyusun material dalam teras, seperti massa dari unsur penyusun elemen bahan bakar nuklir, kelongsong dan air pendingin setelah digunakan dalam teras. Dari perubahan massa tersebut dapat diketahui fraksi bakar atau tingkat konsumsi bahan bakar yang digunakan. Penelitian dilakukan pada basis reaktor PLTN tipe PWR buatan pabrikan asal Amerika Serikat berdaya 1000 MWe dengan menggunakan code penghitung inventori hasil fisi ORIGEN-ARP 5.1, yaitu versi terbaru dari ORIGEN dengan library khusus reaktor daya. Hasil analisis menunjukkan bahwa bahan fisil U-235 mengalami pengurangan massa hingga 58% atau lebih dari separuhnya dari massa U-235 awal untuk tiap kali siklus operasi. Bahan fertil U-238 hanya mengalami pengurangan massa sekitar 2% dari massa awalnya tiap kali siklus operasi. Lain halnya dengan bahan non fisil yang mengalami perubahan massa yang berbeda-beda untuk tiap kali siklus operasinya yang tergantung pada tampang lintang aktivasi serta laju peluruhan dan

  1. High-power electromagnetic wave in a magnetically insulated transmission line of the ANGARA-5-1 facility

    International Nuclear Information System (INIS)

    Samokhin, A. A.

    2010-01-01

    Studies of physical phenomena in magnetically insulated transmission lines (MITLs) of high-power pulsed current generators, analysis of operation of existing megavolt generators, and designing of new high-current generators with a power of up to ∼10 TW require creating an efficient numerical code for modeling the propagation of a high-power electromagnetic pulse in an MITL. This paper presents basic theoretical concepts of MITL operation in the framework of telegraph equations with allowance for electron leakage and variations in the electrode emissivity and analyzes propagation of an electromagnetic wave in the MITLs of the ANGARA-5-1 eight-module facility toward a dynamic load installed in the central unit with a matrix inductance.

  2. Research and development toward a 4.5-1.5{angstrom} linac coherent light source (LCLS) at SLAC

    Energy Technology Data Exchange (ETDEWEB)

    Tatchyn, R.; Arthur, J.; Baltay, M. [Stanford Univ., CA (United States)] [and others

    1995-12-31

    In recent years significant studies have been initiated on the theoretical and technical feasibility of utilizing a portion of the 3km S-band accelerator at the Stanford Linear Accelerator Center (SLAC) to drive a short wavelength (4.5-1.5 {Angstrom}) Linac Coherent Light Source (LCLS), a Free-Electron Laser (FEL) operating in the Self-Amplified Spontaneous Emission (SASE) regime. Electron beam requirements for single-pass saturation include: (1) a peak current in the 3-7 kA range, (2) a relative energy spread of <0.05%, ad (3) a transverse emittance, {epsilon}{le}{lambda}/4{pi}, where {lambda}[m] is the output wavelength. Requirements on the insertion device include field error levels of 0.1-0.2% for keeping the electron bunch centered on and in phase with the amplified photons, and a focusing beta of 4-8 m for inhibiting the dilution of its transverse density. Although much progress techniques necessary for LCLS operation down to {approximately}20 {angstrom}, a substantial amount of research and development is still required in a number of theoretical and experimental areas leading to the construction and operation of a 4.5-1.5 {angstrom} LCLS. In this paper we report on a research and development program underway and in planning at SLAC for addressing critical questions in these areas. These include the construction and operation of a linac test stand for developing laser-driven photocathode rf guns with normalized emittances approaching 1 mm-mr; development of advanced beam compression, stability, an emittance control techniques at multi-GeV energies; the construction and operation of a FEL Amplifier Test Experiment (FATE) for theoretical and experimental studies of SASE at IR wavelengths; an undulator development program to investigate superconducting, hybrid/permanent magnet (hybrid/PM), and pulsed-Cu technologies; theoretical and computational studies of high-gain FEL physics and LCLS component designs.

  3. Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium.

    Science.gov (United States)

    Wrighton, David C; Muench, Stephen P; Lippiat, Jonathan D

    2015-09-01

    The Slo3 (KCa 5.1) channel is a major component of mammalian KSper (sperm potassium conductance) channels and inhibition of these channels by quinine and barium alters sperm motility. The aim of this investigation was to determine the mechanism by which these drugs inhibit Slo3 channels. Mouse (m) Slo3 (KCa 5.1) channels or mutant forms were expressed in Xenopus oocytes and currents recorded with 2-electrode voltage-clamp. Gain-of-function mSlo3 mutations were used to explore the state-dependence of the inhibition. The interaction between quinidine and mSlo3 channels was modelled by in silico docking. Several drugs known to block KSper also affected mSlo3 channels with similar levels of inhibition. The inhibition induced by extracellular barium was prevented by increasing the extracellular potassium concentration. R196Q and F304Y mutations in the mSlo3 voltage sensor and pore, respectively, both increased channel activity. The F304Y mutation did not alter the effects of barium, but increased the potency of inhibition by both quinine and quinidine approximately 10-fold; this effect was not observed with the R196Q mutation. Block of mSlo3 channels by quinine, quinidine and barium is not state-dependent. Barium inhibits mSlo3 outside the cell by interacting with the selectivity filter, whereas quinine and quinidine act from the inside, by binding in a hydrophobic pocket formed by the S6 segment of each subunit. Furthermore, we propose that the Slo3 channel activation gate lies deep within the pore between F304 in the S6 segment and the selectivity filter. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

  4. Space Shuttle Discovery waits in VAB for rollout

    Science.gov (United States)

    2001-01-01

    KENNEDY SPACE CENTER, Fla. -- Viewed from below, Space Shuttle Discovery nearly hides the orange external tank behind it. The twin solid rocket boosters can be seen on either side. Discovery waits in the Vehicle Assembly Building for rollout to Launch Pad 39A. Inclement weather has been a prime factor delaying the rollout. Discovery is scheduled for launch no earlier than Aug. 5 on mission STS-105, carrying the Expedition Three crew that will replace Expedition Two on the International Space Station.

  5. Chance, creativity, and the discovery of the nerve growth factor.

    Science.gov (United States)

    de Romo, Ana Cecilia Rodríguez

    2007-01-01

    This essay analyzes the history of the Nerve Growth Factor (NGF) discovery, relating some of the principles of the theory of scientific creativity to the cognitive and personal qualities of the scientists that participated in the discovery, particularly Rita Levi-Montalcini and Viktor Hamburger. The discovery of NGF is especially attractive for the history of science as it involves chance, luck, creativity, and some extraordinary scientists.

  6. Understanding Self-healing in Service-Discovery Systems

    Science.gov (United States)

    2002-11-01

    service manager (SM) and service user (SU). Figure 1 shows a two-party architecture deployed in a six-component topology: one SM and five SUs. A...sufficient number of SCMs. Upon cessation of aggressive discovery, a component Service Manager Service User Service Cache Manager Aggressive-Discovery... Manager UPnP Multicast Group Unicast Links Figure 2. Three-party service-discovery architecture with five service users (SUs), a service manager (SM), a

  7. How Will We React to the Discovery of Extraterrestrial Life?

    OpenAIRE

    Kwon, Jung Yul; Bercovici, Hannah L.; Cunningham, Katja; Varnum, Michael E. W.

    2018-01-01

    How will humanity react to the discovery of extraterrestrial life? Speculation on this topic abounds, but empirical research is practically non-existent. We report the results of three empirical studies assessing psychological reactions to the discovery of extraterrestrial life using the Linguistic Inquiry and Word Count (LIWC) text analysis software. We examined language use in media coverage of past discovery announcements of this nature, with a focus on extraterrestrial microbial life (Pil...

  8. Conceptual Design For Interplanetary Spaceship Discovery

    Science.gov (United States)

    Benton, Mark G.

    2006-01-01

    With the recently revived national interest in Lunar and Mars missions, this design study was undertaken by the author in an attempt to satisfy the long-term space exploration vision of human travel ``to the Moon, Mars, and beyond'' with a single design or family of vehicles. This paper describes a conceptual design for an interplanetary spaceship of the not-to-distant future. It is a design that is outwardly similar to the spaceship Discovery depicted in the novel ``2001 - A Space Odyssey'' and film of the same name. Like its namesake, this spaceship could one day transport a human expedition to explore the moons of Jupiter. This spaceship Discovery is a real engineering design that is capable of being implemented using technologies that are currently at or near the state-of-the-art. The ship's main propulsion and electrical power are provided by bi-modal nuclear thermal rocket engines. Configurations are presented to satisfy four basic Design Reference Missions: (1) a high-energy mission to Jupiter's moon Callisto, (2) a high-energy mission to Mars, (3) a low-energy mission to Mars, and (4) a high-energy mission to the Moon. The spaceship design includes dual, strap-on boosters to enable the high-energy Mars and Jupiter missions. Three conceptual lander designs are presented: (1) Two types of Mars landers that utilize atmospheric and propulsive braking, and (2) a lander for Callisto or Earth's Moon that utilizes only propulsive braking. Spaceship Discovery offers many advantages for human exploration of the Solar System: (1) Nuclear propulsion enables propulsive capture and escape maneuvers at Earth and target planets, eliminating risky aero-capture maneuvers. (2) Strap-on boosters provide robust propulsive energy, enabling flexibility in mission planning, shorter transit times, expanded launch windows, and free-return abort trajectories from Mars. (3) A backup abort propulsion system enables crew aborts at multiple points in the mission. (4) Clustered NTR

  9. News Shocks in Open Economies: Evidence from Giant Oil Discoveries

    OpenAIRE

    Rabah Arezki; Valerie A. Ramey; Liugang Sheng

    2015-01-01

    This paper explores the effect of news shocks on the current account and other macroeconomic variables using worldwide giant oil discoveries as a directly observable measure of news shocks about future output - the delay between a discovery and production is on average 4 to 6 years. We first present a two-sector small open economy model in order to predict the responses of macroeconomic aggregates to news of an oil discovery. We then estimate the effects of giant oil discoveries on a large pa...

  10. Sentiment Knowledge Discovery in Twitter Streaming Data

    Science.gov (United States)

    Bifet, Albert; Frank, Eibe

    Micro-blogs are a challenging new source of information for data mining techniques. Twitter is a micro-blogging service built to discover what is happening at any moment in time, anywhere in the world. Twitter messages are short, and generated constantly, and well suited for knowledge discovery using data stream mining. We briefly discuss the challenges that Twitter data streams pose, focusing on classification problems, and then consider these streams for opinion mining and sentiment analysis. To deal with streaming unbalanced classes, we propose a sliding window Kappa statistic for evaluation in time-changing data streams. Using this statistic we perform a study on Twitter data using learning algorithms for data streams.

  11. Gideon Mantell and the Discovery of Dinosaurs

    Science.gov (United States)

    Dean, Dennis R.

    1999-01-01

    Gideon Mantell and the Discovery of Dinosaurs is a scholarly yet accessible biography--the first in a generation--of a pioneering dinosaur hunter and scholar. Gideon Mantell discovered the Iguanodon (a famous tale set right in this book) and several other dinosaur species, spent over twenty-five years restoring Iguanodon fossils, and helped establish the idea of an Age of Reptiles that ended with their extinction at the conclusion of the Mesozoic Era. He had significant interaction with such well-known figures as James Parkinson, Georges Cuvier, Charles Lyell, Roderick Murchison, Charles Darwin, and Richard Owen. Dennis Dean, a well-known scholar of geology and the Victorian era, here places Mantell's career in its cultural context, employing original research in archives throughout the world, including the previously unexamined Mantell family papers in New Zealand.

  12. Computational functional group mapping for drug discovery.

    Science.gov (United States)

    Guvench, Olgun

    2016-12-01

    Computational functional group mapping (cFGM) is emerging as a high-impact complement to existing widely used experimental and computational structure-based drug discovery methods. cFGM provides comprehensive atomic-resolution 3D maps of the affinity of functional groups that can constitute drug-like molecules for a given target, typically a protein. These 3D maps can be intuitively and interactively visualized by medicinal chemists to rapidly design synthetically accessible ligands. Given that the maps can inform selection of functional groups for affinity, specificity, and pharmacokinetic properties, they are of utility for both the optimization of existing drug candidates and creating novel ones. Here, I review recent advances in cFGM with emphasis on the unique information content in the approach that offers the potential of broadly facilitating structure-based ligand design. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Functional genomics and cancer drug target discovery.

    Science.gov (United States)

    Moody, Susan E; Boehm, Jesse S; Barbie, David A; Hahn, William C

    2010-06-01

    The recent development of technologies for whole-genome sequencing, copy number analysis and expression profiling enables the generation of comprehensive descriptions of cancer genomes. However, although the structural analysis and expression profiling of tumors and cancer cell lines can allow the identification of candidate molecules that are altered in the malignant state, functional analyses are necessary to confirm such genes as oncogenes or tumor suppressors. Moreover, recent research suggests that tumor cells also depend on synthetic lethal targets, which are not mutated or amplified in cancer genomes; functional genomics screening can facilitate the discovery of such targets. This review provides an overview of the tools available for the study of functional genomics, and discusses recent research involving the use of these tools to identify potential novel drug targets in cancer.

  14. Translational paradigms in pharmacology and drug discovery.

    Science.gov (United States)

    Mullane, Kevin; Winquist, Raymond J; Williams, Michael

    2014-01-01

    The translational sciences represent the core element in enabling and utilizing the output from the biomedical sciences and to improving drug discovery metrics by reducing the attrition rate as compounds move from preclinical research to clinical proof of concept. Key to understanding the basis of disease causality and to developing therapeutics is an ability to accurately diagnose the disease and to identify and develop safe and effective therapeutics for its treatment. The former requires validated biomarkers and the latter, qualified targets. Progress has been hampered by semantic issues, specifically those that define the end product, and by scientific issues that include data reliability, an overt reductionistic cultural focus and a lack of hierarchically integrated data gathering and systematic analysis. A necessary framework for these activities is represented by the discipline of pharmacology, efforts and training in which require recognition and revitalization. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Biomarker Gene Signature Discovery Integrating Network Knowledge

    Directory of Open Access Journals (Sweden)

    Holger Fröhlich

    2012-02-01

    Full Text Available Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches.

  16. Discovery of columnar jointing on Mars

    Science.gov (United States)

    Milazzo, M.P.; Keszthelyi, L.P.; Jaeger, W.L.; Rosiek, M.; Mattson, S.; Verba, C.; Beyer, R.A.; Geissler, P.E.; McEwen, A.S.

    2009-01-01

    We report on the discovery of columnar jointing in Marte Valles, Mars. These columnar lavas were discovered in the wall of a pristine, 16-km-diameter impact crater and exhibit the features of terrestrial columnar basalts. There are discontinuous outcrops along the entire crater wall, suggesting that the columnar rocks covered a surface area of at least 200 km2, assuming that the rocks obliterated by the impact event were similarly jointed. We also see columns in the walls of other fresh craters in the nearby volcanic plains of Elysium Planitia-Amazonis Planitia, which include Marte Vallis, and in a well-preserved crater in northeast Hellas. ?? 2009 The Geological Society of America.

  17. Discovery Monday: How to measure success

    CERN Multimedia

    2003-01-01

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

  18. Atmospheric neutrinos and discovery of neutrino oscillations.

    Science.gov (United States)

    Kajita, Takaaki

    2010-01-01

    Neutrino oscillation was discovered through studies of neutrinos produced by cosmic-ray interactions in the atmosphere. These neutrinos are called atmospheric neutrinos. They are produced as decay products in hadronic showers resulting from collisions of cosmic rays with nuclei in the atmosphere. Electron-neutrinos and muon-neutrinos are produced mainly by the decay chain of charged pions to muons to electrons. Atmospheric neutrino experiments observed zenith-angle and energy dependent deficit of muon-neutrino events. Neutrino oscillations between muon-neutrinos and tau-neutrinos explain these data well. Neutrino oscillations imply that neutrinos have small but non-zero masses. The small neutrino masses have profound implications to our understanding of elementary particle physics and the Universe. This article discusses the experimental discovery of neutrino oscillations.

  19. The Most Important Discovery of Science.

    Science.gov (United States)

    Severinghaus, John W

    2016-01-01

    Oxygen has often been called the most important discovery of science. I disagree. Over five centuries, reports by six scientists told of something in air we animals all need. Three reported how to generate it. It acquired many names, finally oxygen. After 8 years of studying it, Lavoisier still couldn't understand its nature. No special date and no scientist should get credit for discovering oxygen. Henry Cavendish discovered how to make inflammable air (H2). When burned, it made water. This was called impossible because water was assumed to be an element. When Lavoisier repeated the Cavendish test on June 24, 1783, he realized it demolished two theories, phlogiston and water as an element, a Kuhnian paradigm shift that finally unlocked his great revolution of chemistry.

  20. 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.

  1. Natural Products in the Discovery of Agrochemicals.

    Science.gov (United States)

    Loiseleur, Olivier

    2017-12-01

    Natural products have a long history of being used as, or serving as inspiration for, novel crop protection agents. Many of the discoveries in agrochemical research in the last decades have their origin in a wide range of natural products from a variety of sources. In light of the continuing need for new tools to address an ever-changing array of fungal, weed and insect pests, new agricultural practices and evolving regulatory requirements, the needs for new agrochemical tools remains as critical as ever. In that respect, nature continues to be an important source for novel chemical structures and biological mechanisms to be applied for the development of pest control agents. Here we review several of the natural products and their derivatives which contributed to shape crop protection research in past and present.

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

    CERN Document Server

    2006-01-01

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

  3. Financing drug discovery via dynamic leverage.

    Science.gov (United States)

    Montazerhodjat, Vahid; Frishkopf, John J; Lo, Andrew W

    2016-03-01

    We extend the megafund concept for funding drug discovery to enable dynamic leverage in which the portfolio of candidate therapeutic assets is predominantly financed initially by equity, and debt is introduced gradually as assets mature and begin generating cash flows. Leverage is adjusted so as to maintain an approximately constant level of default risk throughout the life of the fund. Numerical simulations show that applying dynamic leverage to a small portfolio of orphan drug candidates can boost the return on equity almost twofold compared with securitization with a static capital structure. Dynamic leverage can also add significant value to comparable all-equity-financed portfolios, enhancing the return on equity without jeopardizing debt performance or increasing risk to equity investors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Chemoselective enrichment for natural products discovery.

    Science.gov (United States)

    Odendaal, Antoinette Y; Trader, Darci J; Carlson, Erin E

    2011-04-01

    Natural products account for a significant proportion of modern day therapeutic agents. However, the discovery of novel compounds is hindered by the isolation process, which often relies upon extraction and chromatographic separation techniques. These methods, which are dependent upon the physicochemical properties of the compounds, have a limited ability to both purify and concentrate the minor components of a biological extract. We have devised an isolation strategy based upon an orthogonal chemical feature, namely, functional group composition. Development of a functional group-targeted method is expected to achieve exceptional resolution given the large number of distinct moieties present in natural product extracts. Here, we describe the generation of controllably reversible covalent enrichment tags for the chemoselective isolation of alcohol-containing natural products from complex mixtures.

  5. Single feature polymorphism discovery in rice.

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar

    Full Text Available The discovery of nucleotide diversity captured as single feature polymorphism (SFP by using the expression array is a high-throughput and effective method in detecting genome-wide polymorphism. The efficacy of such method was tested in rice, and the results presented in the paper indicate high sensitivity in predicting SFP. The sensitivity of polymorphism detection was further demonstrated by the fact that no biasness was observed in detecting SFP with either single or multiple nucleotide polymorphisms. The high density SFP data that can be generated quite effectively by the current method has promise for high resolution genetic mapping studies, as physical location of features are well-defined on rice genome.

  6. Recent discoveries of Uruguayan Mesozoic vertebrates

    International Nuclear Information System (INIS)

    Soto, M.; Perea, D.; Rinderknetch, A.; Ubilla, M.; Da Silva, J.

    2007-01-01

    Recently, new discoveries of Uruguayan Mesozoic vertebrates have been made, as well as the reinterpretation of already known remains. Its taxonomical and biostratigraphical significance justifies this communication. Concerning the Tacuarembo Formation, on one hand a dipnoan prearticular tooth plate has been reinterpreted as belonging to Ceratodus africanus Haug 1905, a species typical of Late Jurassic-Late Cretaceous deposits of Saharan Africa. This is the second dipnoan taxon recorded in the Tacuarembo Formation, uncovering a previously unrecognized dipnoan diversity in the mid-Mesozoic of South America. On the other hand, a few theropod tooth were confidently identified at the familial level for the first time in our country. The remains include two striated premaxillary tooth crowns, the characters of which, close to Ceratosaurus Marsh 1884, allow to refer them to the family Ceratosauridae, this being the oldest South American record of the family. The striated teeth show strong affinities with those of Late Jurassic ceratosaurids from North America, Iberian Peninsula and Tanzania, which is in accordance with recent proposals about the age of the Lower Member of the Tacuarembo Formation. Concerning the Guichon Formation, we comunicate here in the most important discovery of dinosaur remains in Uruguay. It consist in spatially associated remains from several individuals, including fifty caudal vertebra and several epiphysis, metatarsals and astragali. These materials belong to a titanosaurid sauropod, the characters of which are similar to those of certain Campanian-Maastrichtian titanosaurids. Close to the bones, several eggshell fragments referable to Sphaerovum Mones 1980 - a typical Campanian-Maastrichtian oogenus- were found. This finding represents the first record of sauropod dinosaurs from the Guichon Formation, and suggests a younger age for this unit than early proposed

  7. The Process Chain for Peptidomic Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Michael Schrader

    2006-01-01

    Full Text Available Over the last few years the interest in diagnostic markers for specific diseases has increased continuously. It is expected that they not only improve a patient's medical treatment but also contribute to accelerating the process of drug development. This demand for new biomarkers is caused by a lack of specific and sensitive diagnosis in many diseases. Moreover, diseases usually occur in different types or stages which may need different diagnostic and therapeutic measures. Their differentiation has to be considered in clinical studies as well. Therefore, it is important to translate a macroscopic pathological or physiological finding into a microscopic view of molecular processes and vice versa, though it is a difficult and tedious task. Peptides play a central role in many physiological processes and are of importance in several areas of drug research. Exploration of endogenous peptides in biologically relevant sources may directly lead to new drug substances, serve as key information on a new target and can as well result in relevant biomarker candidates. A comprehensive analysis of peptides and small proteins of a biological system corresponding to the respective genomic information (peptidomics®methods was a missing link in proteomics. A new peptidomic technology platform addressing peptides was recently presented, developed by adaptation of the striving proteomic technologies. Here, concepts of using peptidomics technologies for biomarker discovery are presented and illustrated with examples. It is discussed how the biological hypothesis and sample quality determine the result of the study. A detailed study design, appropriate choice and application of technology as well as thorough data interpretation can lead to significant results which have to be interpreted in the context of the underlying disease. The identified biomarker candidates will be characterised in validation studies before use. This approach for discovery of peptide

  8. Energy-Water Nexus Knowledge Discovery Framework

    Science.gov (United States)

    Bhaduri, B. L.; Foster, I.; Chandola, V.; Chen, B.; Sanyal, J.; Allen, M.; McManamay, R.

    2017-12-01

    As demand for energy grows, the energy sector is experiencing increasing competition for water. With increasing population and changing environmental, socioeconomic scenarios, new technology and investment decisions must be made for optimized and sustainable energy-water resource management. This requires novel scientific insights into the complex interdependencies of energy-water infrastructures across multiple space and time scales. An integrated data driven modeling, analysis, and visualization capability is needed to understand, design, and develop efficient local and regional practices for the energy-water infrastructure components that can be guided with strategic (federal) policy decisions to ensure national energy resilience. To meet this need of the energy-water nexus (EWN) community, an Energy-Water Knowledge Discovery Framework (EWN-KDF) is being proposed to accomplish two objectives: Development of a robust data management and geovisual analytics platform that provides access to disparate and distributed physiographic, critical infrastructure, and socioeconomic data, along with emergent ad-hoc sensor data to provide a powerful toolkit of analysis algorithms and compute resources to empower user-guided data analysis and inquiries; and Demonstration of knowledge generation with selected illustrative use cases for the implications of climate variability for coupled land-water-energy systems through the application of state-of-the art data integration, analysis, and synthesis. Oak Ridge National Laboratory (ORNL), in partnership with Argonne National Laboratory (ANL) and researchers affiliated with the Center for International Earth Science Information Partnership (CIESIN) at Columbia University and State University of New York-Buffalo (SUNY), propose to develop this Energy-Water Knowledge Discovery Framework to generate new, critical insights regarding the complex dynamics of the EWN and its interactions with climate variability and change. An overarching

  9. Transpressional Structure in Chiayi Area, Taiwan: Insight from the 2017 ML5.1 Zhongpu Earthquake Sequence

    Science.gov (United States)

    Feng, K. F.; Huang, H. H.

    2017-12-01

    The Chiayi area is located at the deformation front of active fold-and-thrust belt of Taiwan, where the fault system is composed primarily of a series of north-south-trending east-dipping thrusts and also an east-west-trending strike-slip fault (Meishan Fault, MSF) with right-lateral faulting. On 24th May 2017, a ML 5.1 earthquake occurred at Zhongpu, Chiayi (namely Zhongpu earthquake), however, shows a left-lateral strike-slip faulting distinct from the known structure in the area. The distribution of the reported aftershocks is difficult to distinguish the actual fault plane. To determine the fault plane of this abnormal earthquake and investigate its structural relationships to the regional tectonics, we relocate the earthquake sequence and estimate the rupture directivity of the mainshock by using the 3-D double difference hypocenter relocation method (Lin, 2013) and the 3-D directivity moment tensor inversion method (DMT, Huang et al., 2017, submitted). The DMT results show that the rupture directivity of the Zhongpu earthquake is west- and down-ward along the east-west fault plane, which also agrees with east-west-distributed aftershocks after relocation. As a result, the Zhongpu earthquake reveals an undiscovered east-west-trending structure which is sub-parallel with the MSF but with opposite faulting direction, exhibiting a complex transpressional tectonic regime in the Chiayi area.

  10. Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity.

    Science.gov (United States)

    Al-Aif, S; Alvaro, R; Manfreda, J; Kwiatkowski, K; Cates, D; Rigatto, H

    2001-04-01

    Apnea of prematurity is common and none of the treatments being used are fully effective and free of significant adverse side effects. We hypothesized that low concentrations of CO2 (apnea without causing discomfort from an increase in ventilation. We studied 10 preterm infants at a gestational age of 32+/-1 wk (mean +/- SEM) and birthweight 1.8+/-0.2 kg. After a control period of 1 hour, concentrations of CO2 were given (0.5%, 1%, and 1.5%) for 1 hour each, followed by a recovery period of 1 hour. Apnea number significantly decreased from 2.0+/-0.3 apneas/min during control to 1.0+/-0.1 apneas/min (0.5% CO2; P apnea time significantly decreased from 14.2+/-2.5 s/min during control to 5.2+/-0.8 (0.5% CO2; P apnea 1) decreases the number and time of apneas, 2) improves oxygenation, 3) increases ventilation, and 4) is effective even in such low concentrations as 0.5%. We speculate that inhalation of CO2 (treatment of apnea of prematurity.

  11. DInSAR Coseismic Deformation of the May 2011 Mw 5.1 Lorca Earthquake (southeastern Spain

    Directory of Open Access Journals (Sweden)

    F. Pérez

    2012-04-01

    Full Text Available The coseismic superficial deformation at the region of Lorca (Murcia, southeastern Spain due to the Mw 5.1 earthquake on 11 May 2011 was characterized by a multidisciplinary team, integrating information from DInSAR, GPS and numerical modelling techniques. Despite the moderate magnitude of the event, quantitative information was obtained from the interferometric study of a pair of TerraSAR-X images. The DinSAR results defined the trace of the fault plane and evidenced uplift of the hanging wall block in agreement with the estimated deformation obtained through an elastic rupture dislocation numerical model. Meanwhile for the footwall block, interferometric results showed that tectonic deformation is masked by an important subsidence related to groundwater extraction previously identified at the area of study. Horizontal crustal deformation rates and velocity vectors, obtained from GPS stations existent at the area, were also coherent with the tectonic setting of the southern margin of the Iberian Peninsula and with the focal mechanism calculated for the Lorca event. The analysis of a continuous GPS site in Lorca showed good agreement with the horizontal N–S direction component relative to the numerical model and tectonics of the region. This is the first time at this seismic active area that a multi-technique analysis has been performed immediately after the occurrence of a seismic event, comparing the existing deformation data with a theoretical numerical model based on estimated seismic rupture dislocation.

  12. Identification of road user related risk factors, Deliverable 5.1 of the H2020 project SafetyCube (Safety CaUsation, Benefits and Efficiency).

    NARCIS (Netherlands)

    Filtness, A. & Papadimitriou, E. (Eds.) Leskovšek, B. Focant, N. Martensen, H. Sgarra, V. Usami, D.S. Soteropoulos, A. Stadlbauer, S. Theofilatos, A. Yannis, G. Ziakopoulos, A. Diamandouros, K. Durso, C. Goldenbeld, C. Loenis, B. Schermers, G. Petegem, J.-H. van Elvik, R. Hesjevoll, I.S. Quigley, C. & Papazikou, E.

    2017-01-01

    The present Deliverable (D5.1) describes the identification and evaluation of infrastructure related risk factors. It outlines the results of Task 5.1 of WP5 of SafetyCube, which aimed to identify and evaluate infrastructure related risk factors and related road safety problems by (i) presenting a

  13. Polar Localization of the NIP5;1 Boric Acid Channel Is Maintained by Endocytosis and Facilitates Boron Transport in Arabidopsis Roots.

    Science.gov (United States)

    Wang, Sheliang; Yoshinari, Akira; Shimada, Tomoo; Hara-Nishimura, Ikuko; Mitani-Ueno, Namiki; Feng Ma, Jian; Naito, Satoshi; Takano, Junpei

    2017-04-01

    Boron uptake in Arabidopsis thaliana is mediated by nodulin 26-like intrinsic protein 5;1 (NIP5;1), a boric acid channel that is located preferentially on the soil side of the plasma membrane in root cells. However, the mechanism underlying this polar localization is poorly understood. Here, we show that the polar localization of NIP5;1 in epidermal and endodermal root cells is mediated by the phosphorylation of Thr residues in the conserved TPG (ThrProGly) repeat in the N-terminal region of NIP5;1. Although substitutions of Ala for three Thr residues in the TPG repeat did not affect lateral diffusion in the plasma membrane, these substitutions inhibited endocytosis and strongly compromised the polar localization of GFP-NIP5;1. Consistent with this, the polar localization was compromised in µ subunit mutants of the clathrin adaptor AP2. The Thr-to-Ala substitutions did not affect the boron transport activity of GFP-NIP5;1 in Xenopus laevis oocytes but did inhibit the ability to complement boron translocation to shoots and rescue growth defects in nip5;1-1 mutant plants under boron-limited conditions. These results demonstrate that the polar localization of NIP5;1 is maintained by clathrin-mediated endocytosis, is dependent on phosphorylation in the TPG repeat, and is necessary for the efficient transport of boron in roots. © 2017 American Society of Plant Biologists. All rights reserved.

  14. Patterns of species discovery in the Western Ghats, a megadiversity ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Ghats (Flora of Coorg, Flora of Hassan District, Flora of. Udupi, Flora of Tamil Nadu, Flora of Maharashtra, to name a few). Analysis of species discovery curves including four plant and four animal groups indicated a mixed set of patterns. For the charismatic animal species—birds and butterflies—the discovery curve was ...

  15. Evaluation and Comparison of Discovery Tools: An Update

    Directory of Open Access Journals (Sweden)

    F. William Chickering

    2014-06-01

    Full Text Available Abstract: Selection and implementation of a web scale Discovery tool by The Rider University Libraries (RUL in the 2011-2012 academic year revealed the practical complexity of the endeavor. Research into the state of adoption of Web-scale Discovery tools in North America and the evolution of product effectiveness provided a starting point. The study reported here evaluated a total of 14 major Discovery tools (3 open source and 10 proprietary. The evaluation involves a check list of 16 criteria recognized as the advanced features of a modern OPAC. Some of the features have been used in previous research on Discovery tools and the next generation catalog. The authors examined 5 to 7 library websites that deployed a Discovery tool before a determination is made as to the presence or absence of a feature for a particular Discovery tool. The purpose of the study is to evaluate and compare all the major Discovery tools. These findings will serve to update librarians on the latest development in the library user interface and assist them in their adoption of a Discovery tool.

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

    OpenAIRE

    Roberto Raieli

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    David Clark

    2012-01-01

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

  18. Genomics-Driven Natural Product Discovery in Actinomycetes.

    Science.gov (United States)

    Niu, Guoqing

    2018-03-01

    The prevalence of antimicrobial-resistant pathogens has highlighted the urgent need for new drugs. Actinomycetes have been the most prominent sources of natural products for drug discovery and development. Advances in genomics have inspired several emerging strategies to reinvigorate the field of natural product discovery, especially in actinomycete-derived natural products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 10 CFR 2.705 - Discovery-additional methods.

    Science.gov (United States)

    2010-01-01

    ..., or tangible thing. In a proceeding on an application for a construction permit or an operating license for a production or utilization facility, discovery begins only after the prehearing conference... importance of the issue in the proceeding, and the importance of the proposed discovery in resolving the...

  20. Scenario Educational Software: Design and Development of Discovery Learning.

    Science.gov (United States)

    Keegan, Mark

    This book shows how and why the computer is so well suited to producing discovery learning environments. An examination of the literature outlines four basic modes of instruction: didactic, Socratic, inquiry, and discovery. Research from the fields of education, psychology, and physiology is presented to demonstrate the many strengths of…

  1. DHO: Discovery--Stargazing from the Ground Up

    Science.gov (United States)

    O'Leary, Niall

    2013-01-01

    In 2008, the Digital Humanities Observatory was charged with creating an all-island gateway to Irish digital collections and resources. A key factor in the achievement of this goal was the development of the web application, "DHO: Discovery." This chapter will describe what "DHO: Discovery" was intended to be and to what extent…

  2. The rays of life, centennial of discovery of Radium

    International Nuclear Information System (INIS)

    Constantin, Enrique; Plazas, Maria C.

    1999-01-01

    The authors make a recount from the discovery of the rays X for William Conrad Roentgen, in November of 1.985, until our days of the main discoveries and advances in medicine, having like base the radium and their importance in the treatment of the cancer

  3. Promise Fulfilled? An EBSCO Discovery Service Usability Study

    Science.gov (United States)

    Williams, Sarah C.; Foster, Anita K.

    2011-01-01

    Discovery tools are the next phase of library search systems. Illinois State University's Milner Library implemented EBSCO Discovery Service in August 2010. The authors conducted usability studies on the system in the fall of 2010. The aims of the study were twofold: first, to determine how Milner users set about using the system in order to…

  4. Too New for Textbooks: The Biotechnology Discoveries & Applications Guidebook

    Science.gov (United States)

    Loftin, Madelene; Lamb, Neil E.

    2013-01-01

    The "Biotechnology Discoveries and Applications" guidebook aims to provide teachers with an overview of the recent advances in genetics and biotechnology, allowing them to share these findings with their students. The annual guidebook introduces a wealth of modern genomic discoveries and provides teachers with tools to integrate exciting…

  5. Context-aware, ontology-based, service discovery

    NARCIS (Netherlands)

    Broens, T.H.F.; Pokraev, S.; van Sinderen, Marten J.; Koolwaaij, Johan; Dockhorn Costa, P.; Markopoulos, Panos; Eggen, Berry; Aarts, Emile; Crowley, James L.

    2004-01-01

    Service discovery is a process of locating, or discovering, one or more documents, that describe a particular service. Most of the current service discovery approaches perform syntactic matching, that is, they retrieve services descriptions that contain particular keywords from the user’s query.

  6. Discovery-based strategies for studying platelet function.

    Science.gov (United States)

    Flaumenhaft, R; Dilks, J R

    2008-04-01

    The platelet is an anucleate cell, complicating efforts to study platelet function by traditional genetic means. Discovery-based strategies have lead to the identification of pharmacological agents capable of targeting specific proteins critical for platelet activation. This review will address the evolution of discovery-based strategies to identify probes that are at once useful reagents for studying platelet activation and effective therapeutics.

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

    Science.gov (United States)

    Stansfield, William D.

    2012-01-01

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

  8. Discovery Mondays - Neutrinos: journeying with the phantom particles

    CERN Multimedia

    2006-01-01

    There was a record attendance at the last Discovery Monday! Neutrinos and the CNGS facility (CERN Neutrinos to Gran Sasso). There was a record attendance at the last Discovery Monday! Neutrinos and the CNGS facility (CERN Neutrinos to Gran Sasso). A dozen physicists and engineers were stationed at six stands with models and posters.

  9. Delta: the first pion nucleon resonance - its discovery and applications

    International Nuclear Information System (INIS)

    Nagle, D.E.

    1984-07-01

    It is attempted to recapture some of the fun and excitement of the pion-scattering work that led to the discovery of what is now called the delta particle. How significant this discovery was became apparent only gradually. That the delta is alive today and thriving at Los Alamos (as well as other places) is described

  10. 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...

  11. Patterns of species discovery in the Western Ghats, a megadiversity ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    We discuss the trajectories of discovery with respect to rarity or endemicity of the species and life history features, and the ... [Aravind N A, Tambat B, Ravikanth G, Ganeshaiah K N and Uma Shaanker R 2007 Patterns of species discovery in the Western Ghats, a ... charismatic taxa (Tangley 1984; http://biology.usgs.gov/.

  12. A framework for expanding aqueous chemistry in the Community Multiscale Air Quality (CMAQ) model version 5.1

    Science.gov (United States)

    Fahey, Kathleen M.; Carlton, Annmarie G.; Pye, Havala O. T.; Baek, Jaemeen; Hutzell, William T.; Stanier, Charles O.; Baker, Kirk R.; Wyat Appel, K.; Jaoui, Mohammed; Offenberg, John H.

    2017-04-01

    This paper describes the development and implementation of an extendable aqueous-phase chemistry option (AQCHEM - KMT(I)) for the Community Multiscale Air Quality (CMAQ) modeling system, version 5.1. Here, the Kinetic PreProcessor (KPP), version 2.2.3, is used to generate a Rosenbrock solver (Rodas3) to integrate the stiff system of ordinary differential equations (ODEs) that describe the mass transfer, chemical kinetics, and scavenging processes of CMAQ clouds. CMAQ's standard cloud chemistry module (AQCHEM) is structurally limited to the treatment of a simple chemical mechanism. This work advances our ability to test and implement more sophisticated aqueous chemical mechanisms in CMAQ and further investigate the impacts of microphysical parameters on cloud chemistry. Box model cloud chemistry simulations were performed to choose efficient solver and tolerance settings, evaluate the implementation of the KPP solver, and assess the direct impacts of alternative solver and kinetic mass transfer on predicted concentrations for a range of scenarios. Month-long CMAQ simulations for winter and summer periods over the US reveal the changes in model predictions due to these cloud module updates within the full chemical transport model. While monthly average CMAQ predictions are not drastically altered between AQCHEM and AQCHEM - KMT, hourly concentration differences can be significant. With added in-cloud secondary organic aerosol (SOA) formation from biogenic epoxides (AQCHEM - KMTI), normalized mean error and bias statistics are slightly improved for 2-methyltetrols and 2-methylglyceric acid at the Research Triangle Park measurement site in North Carolina during the Southern Oxidant and Aerosol Study (SOAS) period. The added in-cloud chemistry leads to a monthly average increase of 11-18 % in cloud SOA at the surface in the eastern United States for June 2013.

  13. Science of the science, drug discovery and artificial neural networks.

    Science.gov (United States)

    Patel, Jigneshkumar

    2013-03-01

    Drug discovery process many times encounters complex problems, which may be difficult to solve by human intelligence. Artificial Neural Networks (ANNs) are one of the Artificial Intelligence (AI) technologies used for solving such complex problems. ANNs are widely used for primary virtual screening of compounds, quantitative structure activity relationship studies, receptor modeling, formulation development, pharmacokinetics and in all other processes involving complex mathematical modeling. Despite having such advanced technologies and enough understanding of biological systems, drug discovery is still a lengthy, expensive, difficult and inefficient process with low rate of new successful therapeutic discovery. In this paper, author has discussed the drug discovery science and ANN from very basic angle, which may be helpful to understand the application of ANN for drug discovery to improve efficiency.

  14. 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.

  15. Data mining-aided materials discovery and optimization

    Directory of Open Access Journals (Sweden)

    Wencong Lu

    2017-09-01

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

  16. Discovery Approaches for Novel Dyslipidemia Drugs.

    Science.gov (United States)

    Maqbool, Faheem; Safavi, Malihe; Bahadar, Haji; Rahimifard, Mahban; Niaz, Kamal; Abdollahi, Mohammad

    2015-01-01

    Dyslipidemia is increased fasting level of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), along with decreased levels of HDL cholesterol (HDL-C). Owing to effect on the cardiovascular system and increased chances of metabolic diseases, it is needed to review novel under development drugs and new approaches in drug discovery for dyslipidemia. This article reviews all phases I to IV clinical trials and preclinical trials with results associated with novel treatment of dyslipidemia. Drug discovery for dyslipidemia, toward newer targets has been addressed. Statins are, currently available, best choice of drugs for treating dyslipidemia and coronary diseases. In addition to this, lipid lowering drugs support treatment to a great extent, either as monotherapy or in combinations with other groups. Pravastatin used in combination with cholesteryl ester, transfers protein inhibitors (CETP) to produce efficient results. Peroxisome proliferator-activated receptor agonists (PPAR) like muraglitazar, aleglitazar and tesaglitazar are PPAR α/γ receptor agonist, dual in action performs better in phase 3 clinical study and reduces renal and cardiovascular events. By targeting both receptors, a better treatment for cardiovascular and diabetic problems can be achieved. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors like humanized monoclonal antibodies, are newly discovered inhibitors that reduce the risk of cardiovascular diseases. During the past few years, nucleic acid-based therapies targeting lipid and lipoprotein metabolism, such as microsomal TG transfer protein (MTP) may be a promising therapeutic approach to treat vascular diseases. Gene regulating transcription factors involved in bile acids and cholesterol metabolism can be controlled by FXR agonists in dyslipidemia. To overcome these drawbacks, many thyroid hormone analogues have been developed to lower down cholesterol level by targeting specifically thyroid hormone

  17. Using Concepts in Literature-based Discovery: Simulating Swanson's Raynaud-Fish Oil and Migraine-Magnesium Discoveries.

    Science.gov (United States)

    Weeber, Marc; Klein, Henny; de Jong-van den Berg, Lolkje T. W.; Vos, Rein

    2001-01-01

    Proposes a two-step model of discovery in which new scientific hypotheses can be generated and subsequently tested. Applying advanced natural language processing techniques to find biomedical concepts in text, the model is implemented in a versatile interactive discovery support tool. This tool is used to successfully simulate Don R. Swanson's…

  18. 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

  19. The centenary of the discovery of isotopes

    International Nuclear Information System (INIS)

    Soulie, Edgar

    2013-01-01

    This article recalls works performed by different scientists (Marckwald and Keetman, Stromholm and Svedberg, Soddy, Thompson, Aston) which resulted in the observation and identification of the existence of isotopes. The author also recalls various works related to mechanisms of production of isotopes, the discovery of uranium fission and the principle of chain reaction. The author notably evokes French scientists involved in the development of mass spectroscopy and in the research and applications on isotopes within the CEA after the Second World War. A bibliography of article and books published by one of them, Etienne Roth, is provided. References deal with nuclear applications of chemical engineering (heavy water and its production, chemical processes in fission reactors, tritium extraction and enrichment), isotopic fractioning and physical-chemical processes, mass spectrometry and isotopic analysis, isotopic geochemistry (on 07;Earth, search for deuterium in moon rocks and their consequences), first dating and the Oklo phenomenon, radioactive dating, water and climate (isotopic hydrology, isotopes and hailstone formation, the atmosphere), and miscellaneous scientific fields (nuclear measurements and radioactivity, isotopic abundances and atomic weight, isotopic separation and use of steady isotopes)

  20. Discovery Mondays - 'Globe-trotting detectors'

    CERN Multimedia

    2007-01-01

    Transportation of one of the ATLAS barrel toroids (Photo Peter Ginter). From Chicago to Athens via Liverpool, the detector components for the LHC experiments travel high and low before converging on Geneva for their final assembly at CERN. Thousands of scientists from 85 countries across the world are participating in the ALICE, ATLAS, CMS and LHCb experiments, each making their own contribution to the overall project, whether in the production of the sub-detectors, the preparation of the physics or the analysis of the data. At this Discovery Monday you will witness the collaborations' whistle-stop world tour and see some of the extraordinary means of transport that convey the detector parts all the way to CERN's doorstep. All aboard for this remarkable trip around the world in ninety minutes! The event will be conducted in French. Come to the Microcosm (Reception Building 33, Meyrin site) on Monday, 7 May from 7.30 p.m. to 9.00 p.m. Entrance Free http://www.cern.ch/LundisDecouverte/

  1. Discovery Mondays - 'Globe-trotting detectors'

    CERN Multimedia

    2007-01-01

    Transportation of one of the ATLAS barrel toroids (Photo Peter Ginter). From Chicago to Athens via Liverpool, the detector components for the LHC experiments travel high and low before converging on Geneva for their final assembly at CERN. Thousands of scientists from 85 countries across the world are participating in the ALICE, ATLAS, CMS and LHCb experiments, each making their own contribution to the overall project, whether in the production of the sub-detectors, the preparation of the physics or the analysis of the data. At this Discovery Monday you will witness the collaborations' whistle-stop world tour and see some of the extraordinary means of transport that convey the detector parts all the way to CERN's doorstep. All aboard for this remarkable trip around the world in ninety minutes ! The event will be conducted in French. Come to the Microcosm (Reception Building 33, Meyrin site) on Monday, 7 May from 7.30 p.m. to 9.00 p.m. Entrance Free http://www.cern.ch/LundisDecouverte/

  2. Discovery of two new satellites of Pluto.

    Science.gov (United States)

    Weaver, H A; Stern, S A; Mutchler, M J; Steffl, A J; Buie, M W; Merline, W J; Spencer, J R; Young, E F; Young, L A

    2006-02-23

    Pluto's first known satellite, Charon, was discovered in 1978. It has a diameter (approximately 1,200 km) about half that of Pluto, which makes it larger, relative to its primary, than any other moon in the Solar System. Previous searches for other satellites around Pluto have been unsuccessful, but they were not sensitive to objects less, similar150 km in diameter and there are no fundamental reasons why Pluto should not have more satellites. Here we report the discovery of two additional moons around Pluto, provisionally designated S/2005 P 1 (hereafter P1) and S/2005 P 2 (hereafter P2), which makes Pluto the first Kuiper belt object known to have multiple satellites. These new satellites are much smaller than Charon, with estimates of P1's diameter ranging from 60 km to 165 km, depending on the surface reflectivity; P2 is about 20 per cent smaller than P1. Although definitive orbits cannot be derived, both new satellites appear to be moving in circular orbits in the same orbital plane as Charon, with orbital periods of approximately 38 days (P1) and approximately 25 days (P2).

  3. Antimicrobial discovery inspired by ecological interactions.

    Science.gov (United States)

    Molloy, Evelyn M; Hertweck, Christian

    2017-10-01

    Bacteria represent an unparalleled source of antibiotics used to treat infectious diseases. Yet, genome analyses have revealed that their full biosynthetic potential is much larger than expected. Valuable strategies to unearth hidden antibiotics are genome mining, pathway engineering and triggering, as well as co-cultivation approaches. Nevertheless, there is growing understanding that it is often essential to consider the ecological context and that there is a great potential for antimicrobial discovery from bacteria engaged in well-defined interactions with other organisms. Various ecological scenarios involving antimicrobial agents are outlined in this review: predator-prey and pathogenic interactions, the protection of insect assets such as offspring and cultivars, as well as host protection in symbiotic relationships with plants, invertebrates and animals/humans. The illustrative examples given reinforce the idea that examination of interactions between organisms can yield new antimicrobial compounds, and ultimately further our understanding of the function of these molecules in the environment. Copyright © 2017. Published by Elsevier Ltd.

  4. STS-102 Space Shuttle Discovery Liftoff

    Science.gov (United States)

    2003-01-01

    The Space Shuttle Discovery, STS-102 mission, clears launch pad 39B at the Kennedy Space Center as the sun peers over the Atlantic Ocean on March 8, 2001. STS-102's primary cargo was the Leonardo, the Italian Space Agency built Multipurpose Logistics Module (MPLM). The Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS') moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. NASA's 103rd overall flight and the eighth assembly flight, STS-102 was also the first flight involved with Expedition Crew rotation. The Expedition Two crew was delivered to the station while Expedition One was returned home to Earth.

  5. AMS gets lift on space shuttle Discovery

    CERN Multimedia

    2009-01-01

    AMS-02, the CERN-recognized experiment that will seek dark matter, missing matter and antimatter in Space aboard the International Space Station (ISS), has recently got the green light to be part of the STS-134 NASA mission in 2010. Installation of AMS detectors in the Prévessin experiment hall.In a recent press release, NASA announced that the last or last-but-one mission of the Space Shuttle programme would be the one that will deliver AMS, the Alpha Magnetic Spectrometer, to the International Space Station. The Space Shuttle Discovery is due to lift off in July 2010 from Kennedy Space Center and its mission will include the installation of AMS to the exterior of the space station, using both the shuttle and station arms. "It wasn’t easy to get a lift on the Space Shuttle from the Bush administration," says professor Samuel Ting, spokesperson of the experiment, "since during his administration all the funds for space research w...

  6. Torpedo: topic periodicity discovery from text data

    Science.gov (United States)

    Wang, Jingjing; Deng, Hongbo; Han, Jiawei

    2015-05-01

    Although history may not repeat itself, many human activities are inherently periodic, recurring daily, weekly, monthly, yearly or following some other periods. Such recurring activities may not repeat the same set of keywords, but they do share similar topics. Thus it is interesting to mine topic periodicity from text data instead of just looking at the temporal behavior of a single keyword/phrase. Some previous preliminary studies in this direction prespecify a periodic temporal template for each topic. In this paper, we remove this restriction and propose a simple yet effective framework Torpedo to mine periodic/recurrent patterns from text, such as news articles, search query logs, research papers, and web blogs. We first transform text data into topic-specific time series by a time dependent topic modeling module, where each of the time series characterizes the temporal behavior of a topic. Then we use time series techniques to detect periodicity. Hence we both obtain a clear view of how topics distribute over time and enable the automatic discovery of periods that are inherent in each topic. Theoretical and experimental analyses demonstrate the advantage of Torpedo over existing work.

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

    CERN Multimedia

    2007-01-01

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

  8. Discovery Mondays: The very early Universe

    CERN Multimedia

    2003-01-01

    Copyright NASARetracing the very early Universe to understand why there is "something rather than nothing" is one of the challenges facing astrophysics today. It is also the theme of the third Discovery Monday, to be held in the Microcosm on 7 July, where you will be welcomed by a number of scientists. A professional astronomer will allow you to look through his telescope and explain how it works. A cosmologist will talk to you about the very early Universe and a CERN physicist will show you how it's possible to trap antimatter. The mirror of matter, antimatter should have existed in the same quantities as matter in the very early stages of the Universe but today it seems to have virtually disappeared. Perhaps the research being done at CERN will one day explain how an infinitesimal predominance of matter over antimatter resulted in such a richly structured Universe. Come along to the Microcosm on Monday, 7 July between 7.30 p.m. and 9.00 p.m. Entrance is free http://www.cern.ch/microcosm N.B.: The Discove...

  9. The discovery and characterization of riboflavin.

    Science.gov (United States)

    Northrop-Clewes, Christine A; Thurnham, David I

    2012-01-01

    The first observation of a pigment in milk with yellow-green fluorescence can be traced to the English chemist Alexander Wynter Blyth in 1872, but it was not until the early 1930s that the substance was characterized as riboflavin. Interest in accessory food factors began in the latter half of the 19th century with the discovery of the first vitamin, thiamin. Thiamin was water soluble and given the name vitamin B(1). However, researchers realized that there were one or more additional water-soluble factors and these were called the vitamin B-2 complex. The search to identify these accessory food factors in milk, whole wheat, yeast, and liver began in the early 1900s. As there is no classical nutritional disease attributable to riboflavin deficiency, it was the growth-stimulating properties of the food extracts given to young rats that provided the tool with which to investigate and eventually extract riboflavin. Riboflavin was the second vitamin to be isolated and the first from the vitamin B-2 complex; the essential nature of the vitamin as a food constituent for man was shown in 1939. Copyright © 2012 S. Karger AG, Basel.

  10. Targeted drug discovery for pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Andrew D Napper

    2013-07-01

    Full Text Available Despite dramatic advances in the treatment of pediatric leukemia over the past 50 years, there remain subsets of patients who respond poorly to treatment. Many of the high-risk cases of childhood leukemia with the poorest prognosis have been found to harbor specific genetic signatures, often resulting from chromosomal rearrangements. With increased understanding of the genetic and epigenetic makeup of high-risk pediatric leukemia has come the opportunity to develop targeted therapies that promise to be both more effective and less toxic than current chemotherapy. Of particular importance is an understanding of the interconnections between different targets within the same cancer, and observations of synergy between two different targeted therapies or between a targeted drug and conventional chemotherapy. It has become clear that many cancers are able to circumvent a single specific blockade, and pediatric leukemias are no exception in this regard. This review highlights the most promising approaches to new drugs and drug combinations for high-risk pediatric leukemia. Key biological evidence supporting selection of molecular targets is presented, together with a critical survey of recent progress towards the discovery, pre-clinical development, and clinical study of novel molecular therapeutics.

  11. Knowledge Discovery in Data in Construction Projects

    Directory of Open Access Journals (Sweden)

    Szelka J.

    2016-06-01

    Full Text Available Decision-making processes, including the ones related to ill-structured problems, are of considerable significance in the area of construction projects. Computer-aided inference under such conditions requires the employment of specific methods and tools (non-algorithmic ones, the best recognized and successfully used in practice represented by expert systems. The knowledge indispensable for such systems to perform inference is most frequently acquired directly from experts (through a dialogue: a domain expert - a knowledge engineer and from various source documents. Little is known, however, about the possibility of automating knowledge acquisition in this area and as a result, in practice it is scarcely ever used. It has to be noted that in numerous areas of management more and more attention is paid to the issue of acquiring knowledge from available data. What is known and successfully employed in the practice of aiding the decision-making is the different methods and tools. The paper attempts to select methods for knowledge discovery in data and presents possible ways of representing the acquired knowledge as well as sample tools (including programming ones, allowing for the use of this knowledge in the area under consideration.

  12. The discovery of isotopes a complete compilation

    CERN Document Server

    Thoennessen, Michael

    2016-01-01

    This book describes the exciting discovery of every isotope observed on earth to date, which currently numbers some 3000. For each isotope a short essay highlights the authors of the first publication for the isotope, the laboratory and year where and when the isotope was discovered, as well as details about the production and detection methods used. In controversial cases previously claims are also discussed. At the end a comprehensive table lists all isotopes sorted by elements and a complete list of references. Preliminary versions of these paragraphs have been published over the last few years as separate articles in the journal "Atomic Data and Nuclear Data Tables". The work re-evaluates all assignments judging them with a uniform set of criteria. In addition, the author includes over 100 new isotopes which have been discovered since the articles published. This book is a source of information for researchers as well as enthusiastic laymen alike. From the prepublication review: “The explanations focus ...

  13. Discovery Mondays - Mass: a question of weight?

    CERN Multimedia

    2006-01-01

    Mass and weight: two rather commonplace phenomena on the surface of it, but would you be able to explain the difference between them? And do you know how gravity works? If you let go of a paperclip and an apple at the same time, which of the two will hit the floor first? At the next Discovery Monday scientists will introduce you to these concepts that are often rather difficult to get to grips with. Find out what kind of particles are thought to be responsible for mass and gravity. Get to know the graviton, a particle that has yet to be observed, has no mass or charge but is thought to be a messenger particle for gravity. You will also encounter the famous Higgs boson, which scientists believe could elucidate the mystery of mass and hope to discover with the LHC. An evening for tackling some very weighty questions... The event will be conducted in French. Join us at Microcosm (Reception, Building 33, Meyrin site), on Monday 6 March from 7.30 p.m. to 9.00 p.m. Entrance Free http://www.cern.ch/LundisDeco...

  14. Faults Discovery By Using Mined Data

    Science.gov (United States)

    Lee, Charles

    2005-01-01

    Fault discovery in the complex systems consist of model based reasoning, fault tree analysis, rule based inference methods, and other approaches. Model based reasoning builds models for the systems either by mathematic formulations or by experiment model. Fault Tree Analysis shows the possible causes of a system malfunction by enumerating the suspect components and their respective failure modes that may have induced the problem. The rule based inference build the model based on the expert knowledge. Those models and methods have one thing in common; they have presumed some prior-conditions. Complex systems often use fault trees to analyze the faults. Fault diagnosis, when error occurs, is performed by engineers and analysts performing extensive examination of all data gathered during the mission. International Space Station (ISS) control center operates on the data feedback from the system and decisions are made based on threshold values by using fault trees. Since those decision-making tasks are safety critical and must be done promptly, the engineers who manually analyze the data are facing time challenge. To automate this process, this paper present an approach that uses decision trees to discover fault from data in real-time and capture the contents of fault trees as the initial state of the trees.

  15. The discovery and development of antiretroviral agents.

    Science.gov (United States)

    Lange, Joep M A; Ananworanich, Jintanat

    2014-01-01

    Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral replication to minimal levels. It was then widely felt, however, that HAART was too expensive and complex for low- and middle-income countries, and so, with the exception of a few of these countries, such as Brazil, a massive scale-up did not begin until the WHO launched its '3 by 5' initiative and sizeable funding mechanisms, such as the Global Fund to Fight AIDS, TB and Malaria and the US President's Emergency Plan for AIDS Relief (PEPFAR), came into existence. A pivotal enabler of the scale-up was a steady lowering of drug prices through entry of generic antiretrovirals, competition between generic manufacturers and the making of volume commitments. The WHO Prequalification of Medicines Programme and the Expedited Review Provision of the US Food and Drug Administration have been important for the assurance of quality standards. Antiretroviral drug development by research-based pharmaceutical companies continues, with several important innovative products, such as long-acting agents, in the pipeline.

  16. Asymmetric threat data mining and knowledge discovery

    Science.gov (United States)

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

    2001-03-01

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

  17. Discovery Mondays: 'The Grid: a universal computer'

    CERN Multimedia

    2006-01-01

    How can one store and analyse the 15 million billion pieces of data that the LHC will produce each year with a computer that isn't the size of a sky-scraper? The IT experts have found the answer: the Grid, which will harness the power of tens of thousands of computers in the world by putting them together on one network and making them work like a single computer achieving a power that has not yet been matched. The Grid, inspired from the Web, already exists - in fact, several of them exist in the field of science. The European EGEE project, led by CERN, contributes not only to the study of particle physics but to medical research as well, notably in the study of malaria and avian flu. The next Discovery Monday invites you to explore this futuristic computing technology. The 'Grid Masters' of CERN have prepared lively animations to help you understand how the Grid works. Children can practice saving the planet on the Grid video game. You will also discover other applications such as UNOSAT, a United Nations...

  18. Discovery of Allostery in PKA Signaling.

    Science.gov (United States)

    Zhang, Ping; Kornev, Alexandr P; Wu, Jian; Taylor, Susan S

    2015-06-01

    cAMP-dependent protein kinase (PKA) was the second protein kinase to be discovered and the PKA catalytic (C) subunit serves as a prototype for the large protein kinase superfamily that contains over 500 gene products. The protein kinases regulate much of biology in eukaryotic cells and they are now also a major therapeutic target. Although PKA was discovered nearly 50 years ago and the subsequent discovery of the regulatory subunits that bind cAMP and release the catalytic activity from the holoenzyme followed quickly. Thus in PKA we see the convergence of two major signaling mechanisms - protein phosphorylation and second messenger signaling through cAMP. Crystallography provides a foundation for understanding function, and the structure of the isolated regulatory (R) and C-subunits have been extremely informative. Yet it is the R 2 C 2 holoenzyme that predominates in cells, and one can only appreciate the allosteric features of PKA signaling by seeing the full length protein. The symmetry and the quaternary constraints that one R:C hetero-dimer exerts on the other in the holoenzyme simply are not present in the isolated subunits or even in the R:C hetero-dimer.

  19. Discovery Mondays: 'Separating science from fiction'

    CERN Document Server

    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/ ...

  20. Percolator: Scalable Pattern Discovery in Dynamic Graphs

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Sutanay; Purohit, Sumit; Lin, Peng; Wu, Yinghui; Holder, Lawrence B.; Agarwal, Khushbu

    2018-02-06

    We demonstrate Percolator, a distributed system for graph pattern discovery in dynamic graphs. In contrast to conventional mining systems, Percolator advocates efficient pattern mining schemes that (1) support pattern detection with keywords; (2) integrate incremental and parallel pattern mining; and (3) support analytical queries such as trend analysis. The core idea of Percolator is to dynamically decide and verify a small fraction of patterns and their in- stances that must be inspected in response to buffered updates in dynamic graphs, with a total mining cost independent of graph size. We demonstrate a) the feasibility of incremental pattern mining by walking through each component of Percolator, b) the efficiency and scalability of Percolator over the sheer size of real-world dynamic graphs, and c) how the user-friendly GUI of Percolator inter- acts with users to support keyword-based queries that detect, browse and inspect trending patterns. We also demonstrate two user cases of Percolator, in social media trend analysis and academic collaboration analysis, respectively.

  1. Discovery Mondays: "Robots: At your service!"

    CERN Multimedia

    2005-01-01

    Two of the ISOLDE robots. Robots at CERN? Yes, because their presence is essential for replacing human beings when some tasks are too difficult for them, for example when materials are too fragile or too risky to work with. Come and discover the ISOLDE robots. You will also be able to meet "the Crab", in charge of carrying the LHC magnets in its claws. EPFL engineers from Autonomous Systems Lab and the Laboratory of Intelligent Systems will introduce you to some of their creations, including a robot built for planetary exploration, an indoor flying robot and a microrobot as tiny as a lump of sugar. At the next Discovery Monday, you will have the opportunity to meet robots of many sizes and forms. You will be amazed by their diversity and their personalities. Join us at the Microcosm (Reception Building 33, Meyrin site) on Monday 4 April from 7.30 p.m. to 9.00 p.m. Entrance Free http://www.cern.ch/microcosm http://intranet.cern.ch/Microcosm/LundisDecouverte/

  2. Discovery Mondays: "Robots: At your service!"

    CERN Document Server

    2005-01-01

    Two of the ISOLDE robots. Robots at CERN? Yes, because their presence is essential for replacing human beings when some tasks are too difficult for them, for example when materials are too fragile or too risky to work with. Come and discover the ISOLDE robots. You will also be able to meet "the Crab", in charge of carrying the LHC magnets in its claws. EPFL engineers from Autonomous Systems Lab and the Laboratory of Intelligent Systems will introduce you to some of their creations, including a robot built for planetary exploration, an indoor flying robot and a microrobot as tiny as a lump of sugar. At the next Discovery Monday, you will have the opportunity to meet robots of many sizes and forms. You will be amazed by their diversity and their personalities. Join us at the Microcosm (Reception Building 33, Meyrin site) on Monday 4 April from 7.30 p.m. to 9.00 p.m. Entrance Free http://www.cern.ch/microcosm http://cern.ch/lundisdecouverte

  3. Discovery Monday: Much ado about nothing: vacuums

    CERN Multimedia

    2004-01-01

    Most people seem to agree that an empty space has nothing in it. But what about the physicists? "Wait a minute!", they will tell you, at the Microcosm's next Discovery Monday on 5th April, for they know that even interstellar space is not as empty as it might seem... Because particles, the tiny constituents of matter, are everywhere. Even the most sophisticated vacuum pumps cannot get rid of them all. What's more, energy is omnipresent in the Universe. Energy has the habit of turning itself into matter then disappearing, only to come back again as energy... and all this in the twinkling of an eye. Hence the term "virtual matter". A completely empty space simply does not exist. Vacuums are of vital importance to CERN's physicists. In the accelerators, it is essential to obtain the best possible vacuum inside the tube through which the particles travel, in order to avoid interference from other, stray particles. To this end they use "getter" strips, which act like fly traps. When these strip...

  4. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  5. The Higgs Boson Search and Discovery

    CERN Document Server

    Bernardi, Gregorio

    2016-01-01

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

  6. Knowledge Discovery in Literature Data Bases

    Science.gov (United States)

    Albrecht, Rudolf; Merkl, Dieter

    The concept of knowledge discovery as defined through ``establishing previously unknown and unsuspected relations of features in a data base'' is, cum grano salis, relatively easy to implement for data bases containing numerical data. Increasingly we find at our disposal data bases containing scientific literature. Computer assisted detection of unknown relations of features in such data bases would be extremely valuable and would lead to new scientific insights. However, the current representation of scientific knowledge in such data bases is not conducive to computer processing. Any correlation of features still has to be done by the human reader, a process which is plagued by ineffectiveness and incompleteness. On the other hand we note that considerable progress is being made in an area where reading all available material is totally prohibitive: the World Wide Web. Robots and Web crawlers mine the Web continuously and construct data bases which allow the identification of pages of interest in near real time. An obvious step is to categorize and classify the documents in the text data base. This can be used to identify papers worth reading, or which are of unexpected cross-relevance. We show the results of first experiments using unsupervised classification based on neural networks.

  7. Computational Analyses for Transplant Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Anyou eWang

    2015-09-01

    Full Text Available Translational medicine offers a rich promise for improved diagnostics and drug discovery for biomedical research in the field of transplantation, where continued unmet diagnostic and therapeutic needs persist. Current advent of genomics and proteomics profiling called omics provides new resources to develop novel biomarkers for clinical routine. Establishing such a marker system heavily depends on appropriate applications of computational algorithms and software, which are basically based on mathematical theories and models. Understanding these theories would help to apply appropriate algorithms to ensure biomarker systems successful. Here, we review the key advances in theories and mathematical models relevant to transplant biomarker developments. Advantages and limitations inherent inside these models are discussed. The principles of key computational approaches for selecting efficiently the best subset of biomarkers from high dimensional omics data are highlighted. Prediction models are also introduced and the integration of multi-microarray data is also discussed. Appreciating these key advances would help to accelerate the development of clinically reliable biomarker systems.

  8. Brivaracetam: a rational drug discovery success story

    Science.gov (United States)

    Rogawski, M A

    2008-01-01

    Levetiracetam, the α-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a ∼90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity in animal seizure models. Recent phase II clinical trials demonstrating that brivaracetam is efficacious and well tolerated in the treatment of partial onset seizures have validated the strategy of the discovery programme. Brivaracetam is among the first clinically effective AEDs to be discovered by optimization of pharmacodynamic activity at a molecular target. PMID:18552880

  9. Web proxy auto discovery for the WLCG

    CERN Document Server

    Dykstra, D; Blumenfeld, B; De Salvo, A; Dewhurst, A; Verguilov, V

    2017-01-01

    All four of the LHC experiments depend on web proxies (that is, squids) at each grid site to support software distribution by the CernVM FileSystem (CVMFS). CMS and ATLAS also use web proxies for conditions data distributed through the Frontier Distributed Database caching system. ATLAS & CMS each have their own methods for their grid jobs to find out which web proxies to use for Frontier at each site, and CVMFS has a third method. Those diverse methods limit usability and flexibility, particularly for opportunistic use cases, where an experiment’s jobs are run at sites that do not primarily support that experiment. This paper describes a new Worldwide LHC Computing Grid (WLCG) system for discovering the addresses of web proxies. The system is based on an internet standard called Web Proxy Auto Discovery (WPAD). WPAD is in turn based on another standard called Proxy Auto Configuration (PAC). Both the Frontier and CVMFS clients support this standard. The input into the WLCG system comes from squids regis...

  10. Discovery of Intrinsic Primitives on Triangle Meshes

    KAUST Repository

    Solomon, Justin

    2011-04-01

    The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones as the building blocks of shapes, and thus to discover parts by fitting such primitives to a given surface. This approach, however, will break down if primitive parts have undergone almost-isometric deformations, as is the case, for example, for articulated human models. We suggest that parts can be discovered instead by finding intrinsic primitives, which we define as parts that posses an approximate intrinsic symmetry. We employ the recently-developed method of computing discrete approximate Killing vector fields (AKVFs) to discover intrinsic primitives by investigating the relationship between the AKVFs of a composite object and the AKVFs of its parts. We show how to leverage this relationship with a standard clustering method to extract k intrinsic primitives and remaining asymmetric parts of a shape for a given k. We demonstrate the value of this approach for identifying the prominent symmetry generators of the parts of a given shape. Additionally, we show how our method can be modified slightly to segment an entire surface without marking asymmetric connecting regions and compare this approach to state-of-the-art methods using the Princeton Segmentation Benchmark. © 2011 The Author(s).

  11. Discovery of potassium salts deposits in colombia

    International Nuclear Information System (INIS)

    Gonzalez Oviedo Leopoldo; Espinosa Baquero Armando

    2012-01-01

    The first potassium salts ores found in Colombia are presented and described; they are located in the Santander province, in La Mesa de los Santos area, between Los Santos village and the rio Chicamocha Canyon. From a geological point of view, the mineralization is associated to the sediments of the Paja Formation, Early Cretaceous in age, and is located near the base of the formation. In the study area the main structure is the Villanueva syncline which involves, from bottom to top, Los Santos, Rosablanca, Paja, Tablazo and Simiti formations.The mineralization consists of small veins where the main mineral is singenite (K 2 Ca[SO4] 2- H 2 O) with small amounts of carbonates and accidental minerals. In the host rock, minerals like langbeinite (K 2 Mg 2 [SO4] 3) andrinneite (K 3 Na[Fe,Cl] 6) are present; they show that the rock was formed in an evaporitic environment and that detailed studies of that sequence may lead to the discovery of other mineralizations of economic interest.

  12. Impact of the CYP3A5*1 Allele on the Pharmacokinetics of Tacrolimus in Japanese Heart Transplant Patients.

    Science.gov (United States)

    Uno, Takaya; Wada, Kyoichi; Matsuda, Sachi; Terada, Yuka; Oita, Akira; Kawase, Atsushi; Takada, Mitsutaka

    2018-04-24

    Tacrolimus, a major immunosuppressant used after transplantation, is associated with large interindividual variation involving genetic polymorphisms in metabolic processes. A common variant of the cytochrome P450 (CYP) 3A5 gene, CYP3A5*3, affects blood concentrations of tacrolimus. However, tacrolimus pharmacokinetics at the early stage of transplantation have not been adequately studied in heart transplantation. We retrospectively examined the impact of the CYP3A5 genotype on tacrolimus pharmacokinetics at the early stage of heart transplantation. The tacrolimus pharmacokinetic profile was obtained from 65 patients during the first 5 weeks after heart transplantation. Differences in the patients' characteristics and tacrolimus pharmacokinetic parameters between the CYP3A5 expresser (*1/*1 or *1/*3 genotypes) and non-expresser (*3/*3 genotype) groups were assessed by the Chi-square test, Student's t test, or Mann-Whitney U test. The CYP3A5 *1/*1, *1/*3, and *3/*3 genotypes were detected in 5, 22, and 38 patients, respectively. All patients started clotrimazole therapy approximately 1 week after starting tacrolimus. Apparent clearance and dose/weight to reach the target trough concentration (C 0 ) were significantly higher in the expresser group than in the non-expresser group (0.32 vs. 0.19 L/h/kg, p = 0.0003; 0.052 vs. 0.034 mg/kg/day, p = 0.0002); there were no significant differences in the area under the concentration-time curve from 0 to 12 h (AUC 0-12 ) and concentrations at any sampling time point between the two groups. Similar concentration-time curves for tacrolimus were obtained in the expresser and non-expresser groups by dose adjustment based on therapeutic drug monitoring. These results demonstrate the importance of the CYP3A5 genotype in tacrolimus dose optimization based on therapeutic drug monitoring after heart transplantation.

  13. A brief history of the ''Delayed'' discovery of nuclear fission

    International Nuclear Information System (INIS)

    Holden, N.E.

    1989-08-01

    This year marks the Fiftieth Anniversary of the discovery of Nuclear Fission. In the early 1930's, the neutron was discovered, followed by the discovery of artificial radioactivity and then the use of the neutron to produce artificial radioactivity. The first experiments resulting in the fission of uranium took place in 1934. A paper which speculated on fission as an explanation was almost immediately published, yet no one took it seriously not even the author herself. Why did it take an additional five years before anyone realized what had occurred? This is an abnormally long time in a period when discoveries, particularly in nuclear physics, seemed to be almost a daily occurrence. The events which led up to the discovery are recounted, with an attempt made to put them into their historical perspective. The role played by Mendeleev's Periodic Table, the role of the natural radioactive decay chain of uranium, the discovery of protactinium, the apparent discovery of masurium (technetium) and a speculation on the reason why Irene Curie may have missed the discovery of nuclear fission will all be discussed. 43 refs

  14. 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.

  15. 4 km NODC/RSMAS AVHRR Pathfinder Version 5.0 and 5.1 Daily Harmonic Climatologies (1982-2008) (NODC Accession 0071181)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains a global, 4km daily sea surface temperature climatology derived from harmonic analysis of the AVHRR Pathfinder Version 5.0 and 5.1 sea...

  16. 4 km NODC/RSMAS AVHRR Pathfinder Version 5.0 and 5.1 Monthly Harmonic Climatologies (1982-2008) (NODC Accession 0075098)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains a global, 4km monthly sea surface temperature climatology derived from harmonic analysis of the AVHRR Pathfinder Version 5.0 and 5.1 sea...

  17. 4 km NODC/RSMAS AVHRR Pathfinder Version 5.0 and 5.1 5-day Harmonic Climatologies (1982-2008) (NODC Accession 0071182)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains a global, 4km 5-day sea surface temperature climatology derived from harmonic analysis of the AVHRR Pathfinder Version 5.0 and 5.1 sea...

  18. Space Shuttle Discovery on Launch Pad 39A

    Science.gov (United States)

    2000-01-01

    The flag at right identifies Space Shuttle Discovery on Launch Pad 39A after its rollout and before the Rotating Service Structure is moved around it. Scheduled to launch Oct. 5 at 9:38 p.m. EDT on mission STS-92, Discovery will be making the 100th Space Shuttle mission launched from Kennedy Space Center. Discovery also will be making its 28th flight into space, more than any of the other orbiters to date. STS-92 is a mission to the International Space Station, carrying the Z1 truss, which is the first of 10 trusses on the Station, and the third Pressurized Mating Adapter.

  19. Advancing Geoscience Resource Discovery with Cutting-Edge Cyberinfrastructure Technologies

    Science.gov (United States)

    Yang, C. P.

    2016-12-01

    Resources including data, facilities, experts, capabilities, and others are of critical importance to advance geosciences. Identify the most proper and available resource is part of the resource discovery field. This paper will report the experiences on how resource discovery has been advanced in the past decade using several experiences including FGDC NSDI, GEOSS Clearinghouse, NASA AIST MUDROD, and a Planetary Defense data archiving system. Technically, data quality, spatiotemporal matches, semantic based meaning discovery, and other factors will be discussed and are considered in the practices.

  20. 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...

  1. Planetary Sciences Literature - Access and Discovery

    Science.gov (United States)

    Henneken, Edwin A.; ADS Team

    2017-10-01

    The NASA Astrophysics Data System (ADS) has been around for over 2 decades, helping professional astronomers and planetary scientists navigate, without charge, through the increasingly complex environment of scholarly publications. As boundaries between disciplines dissolve and expand, the ADS provides powerful tools to help researchers discover useful information efficiently. In its new form, code-named ADS Bumblebee (https://ui.adsabs.harvard.edu), it may very well answer questions you didn't know you had! While the classic ADS (http://ads.harvard.edu) focuses mostly on searching basic metadata (author, title and abstract), today's ADS is best described as a an "aggregator" of scholarly resources relevant to the needs of researchers in astronomy and planetary sciences, and providing a discovery environment on top of this. In addition to indexing content from a variety of publishers, data and software archives, the ADS enriches its records by text-mining and indexing the full-text articles (about 4.7 million in total, with 130,000 from planetary science journals), enriching its metadata through the extraction of citations and acknowledgments. Recent technology developments include a new Application Programming Interface (API), a new user interface featuring a variety of visualizations and bibliometric analysis, and integration with ORCID services to support paper claiming. The new ADS provides powerful tools to help you find review papers on a given subject, prolific authors working on a subject and who they are collaborating with (within and outside their group) and papers most read by by people who read recent papers on the topic of your interest. These are just a couple of examples of the capabilities of the new ADS. We currently index most journals covering the planetary sciences and we are striving to include those journals most frequently cited by planetary science publications. The ADS is operated by the Smithsonian Astrophysical Observatory under NASA

  2. False discovery rates: a new deal.

    Science.gov (United States)

    Stephens, Matthew

    2017-04-01

    We introduce a new Empirical Bayes approach for large-scale hypothesis testing, including estimating false discovery rates (FDRs), and effect sizes. This approach has two key differences from existing approaches to FDR analysis. First, it assumes that the distribution of the actual (unobserved) effects is unimodal, with a mode at 0. This "unimodal assumption" (UA), although natural in many contexts, is not usually incorporated into standard FDR analysis, and we demonstrate how incorporating it brings many benefits. Specifically, the UA facilitates efficient and robust computation-estimating the unimodal distribution involves solving a simple convex optimization problem-and enables more accurate inferences provided that it holds. Second, the method takes as its input two numbers for each test (an effect size estimate and corresponding standard error), rather than the one number usually used ($p$ value or $z$ score). When available, using two numbers instead of one helps account for variation in measurement precision across tests. It also facilitates estimation of effects, and unlike standard FDR methods, our approach provides interval estimates (credible regions) for each effect in addition to measures of significance. To provide a bridge between interval estimates and significance measures, we introduce the term "local false sign rate" to refer to the probability of getting the sign of an effect wrong and argue that it is a superior measure of significance than the local FDR because it is both more generally applicable and can be more robustly estimated. Our methods are implemented in an R package ashr available from http://github.com/stephens999/ashr. © The Author 2016. Published by Oxford University Press.

  3. Error-free 5.1 Tbit/s data generation on a single-wavelength channel using a 1.28 Tbaud symbol rate

    DEFF Research Database (Denmark)

    Mulvad, Hans Christian Hansen; Galili, Michael; Oxenløwe, Leif Katsuo

    2009-01-01

    We demonstrate a record bit rate of 5.1 Tbit/s on a single wavelength using a 1.28 Tbaud OTDM symbol rate, DQPSK data-modulation, and polarisation-multiplexing. Error-free performance (BER......We demonstrate a record bit rate of 5.1 Tbit/s on a single wavelength using a 1.28 Tbaud OTDM symbol rate, DQPSK data-modulation, and polarisation-multiplexing. Error-free performance (BER...

  4. Theoretical reaction pathways for the formation of (Si(OH)5)(1-) and the deprotonation of orthosilicic acid in basic solution

    Science.gov (United States)

    Kubicki, J. D.; Xiao, Y.; Lasaga, A. C.

    1993-01-01

    The stability of (Si(OH)5)(1-) is predicted by means of molecular orbital calculations. Si is predicted to be as stable in basic aqueous solutions as hydrated (/OH/3SiO)(1-) and more stable than Si(OH)4 + (OH)(1-). Vibrational analysis of (Si(OH)5)(1-) predicts Raman and IR spectra that are not compatible with the presence of Si in some silicate glasses under ambient temperature compression.

  5. Challenges of manpower in nursing | Bola | Discovery and Innovation

    African Journals Online (AJOL)

    Discovery and Innovation. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 17 (2005) >. Log in or Register to get access to full text downloads.

  6. Open discovery: An integrated live Linux platform of Bioinformatics tools.

    Science.gov (United States)

    Vetrivel, Umashankar; Pilla, Kalabharath

    2008-01-01

    Historically, live linux distributions for Bioinformatics have paved way for portability of Bioinformatics workbench in a platform independent manner. Moreover, most of the existing live Linux distributions limit their usage to sequence analysis and basic molecular visualization programs and are devoid of data persistence. Hence, open discovery - a live linux distribution has been developed with the capability to perform complex tasks like molecular modeling, docking and molecular dynamics in a swift manner. Furthermore, it is also equipped with complete sequence analysis environment and is capable of running windows executable programs in Linux environment. Open discovery portrays the advanced customizable configuration of fedora, with data persistency accessible via USB drive or DVD. The Open Discovery is distributed free under Academic Free License (AFL) and can be downloaded from http://www.OpenDiscovery.org.in.

  7. Biomarker discovery in high grade sarcomas by mass spectrometry imaging

    OpenAIRE

    Lou, S.

    2017-01-01

    This thesis demonstrates a detailed biomarker discovery Mass Spectrometry Imaging workflow for histologically heterogeneous high grade sarcomas. Panels of protein and metabolite signatures were discovered either distinguishing different histological subtypes or stratifying high risk patients with poor survival.

  8. J.J. Thompson and the discovery of the electron

    CERN Document Server

    Davis, E A

    2002-01-01

    This historical survey of the discovery of the electron has been published to coincide with the centenary of the discovery. The text maps the life and achievements of J.J. Thomson, with particular focus on his ideas and experiments leading to the discovery. It describes Thomson''s early years and education. It then considers his career at Cambridge, first as a fellow of Trinity, later as the head of the Cavendish Laboratory and finally as Master of Trinity and national spokesman for science. The core of the book is concerned with the work undertaken at the Cavendish, culminating in the discovery of "corpuscles", later named "electrons".; In the final two chapters, the immediate aftermath and implications of the work are described. These include the creation of the subject of atomic physics as well as the broader long term developments which can be traced from vacuum valves and the transistor through to the microelectronics revolution.

  9. ASTEROID NAMES AND DISCOVERY V7.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set lists name, designation(s), and discovery circumstances for all asteroids numbered as of the given stop date. It is compiled and maintain by David...

  10. ASTEROID NAMES AND DISCOVERY V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes names, designations, and discovery circumstances for the numbered asteroids, sorted in order of catalog number. A similar file sorted in...

  11. 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

  12. Advances in Chance Discovery : Extended Selection from International Workshops

    CERN Document Server

    Abe, Akinori

    2013-01-01

    Since year 2000, scientists on artificial and natural intelligences started to study chance discovery - methods for discovering events/situations that significantly affect decision making. Partially because the editors Ohsawa and Abe are teaching at schools of Engineering and of Literature with sharing the interest in chance discovery, this book reflects interdisciplinary aspects of progress: First, as an interdisciplinary melting pot of cognitive science, computational intelligence, data mining/visualization, collective intelligence, … etc, chance discovery came to reach new application domains e.g. health care, aircraft control, energy plant, management of technologies, product designs, innovations, marketing, finance etc. Second, basic technologies and sciences including sensor technologies, medical sciences, communication technologies etc. joined this field and interacted with cognitive/computational scientists in workshops on chance discovery, to obtain breakthroughs by stimulating each other. Third, �...

  13. Effectiveness of discovery learning model on mathematical problem solving

    Science.gov (United States)

    Herdiana, Yunita; Wahyudin, Sispiyati, Ririn

    2017-08-01

    This research is aimed to describe the effectiveness of discovery learning model on mathematical problem solving. This research investigate the students' problem solving competency before and after learned by using discovery learning model. The population used in this research was student in grade VII in one of junior high school in West Bandung Regency. From nine classes, class VII B were randomly selected as the sample of experiment class, and class VII C as control class, which consist of 35 students every class. The method in this research was quasi experiment. The instrument in this research is pre-test, worksheet and post-test about problem solving of mathematics. Based on the research, it can be conclude that the qualification of problem solving competency of students who gets discovery learning model on level 80%, including in medium category and it show that discovery learning model effective to improve mathematical problem solving.

  14. Context-sensitive service discovery experimental prototype and evaluation

    DEFF Research Database (Denmark)

    Balken, Robin; Haukrogh, Jesper; L. Jensen, Jens

    2007-01-01

    The amount of different networks and services available to users today are increasing. This introduces the need for a way to locate and sort out irrelevant services in the process of discovering available services to a user. This paper describes and evaluates a prototype of an automated discovery...... and selection system, which locates services relevant to a user, based on his/her context and the context of the available services. The prototype includes a multi-level, hierarchical system approach and the introduction of entities called User-nodes, Super-nodes and Root-nodes. These entities separate...... the network in domains that handle the complex distributed service discovery, which is based on dynamically changing context information. In the prototype, a method for performing context-sensitive service discovery has been realised. The service discovery part utilizes UPnP, which has been expanded in order...

  15. 5 CFR 1201.72 - Explanation and scope of discovery.

    Science.gov (United States)

    2010-01-01

    ... information is obtained to assist the parties in preparing and presenting their cases. The Federal Rules of... discovery methods permitted by these regulations. Such limitations may be imposed if the judge finds that...

  16. 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,

  17. Integration of distributed computing into the drug discovery process.

    Science.gov (United States)

    von Korff, Modest; Rufener, Christian; Stritt, Manuel; Freyss, Joel; Bär, Roman; Sander, Thomas

    2011-02-01

    Grid computing offers an opportunity to gain massive computing power at low costs. We give a short introduction into the drug discovery process and exemplify the use of grid computing for image processing, docking and 3D pharmacophore descriptor calculations. The principle of a grid and its architecture are briefly explained. More emphasis is laid on the issues related to a company-wide grid installation and embedding the grid into the research process. The future of grid computing in drug discovery is discussed in the expert opinion section. Most needed, besides reliable algorithms to predict compound properties, is embedding the grid seamlessly into the discovery process. User friendly access to powerful algorithms without any restrictions, that is, by a limited number of licenses, has to be the goal of grid computing in drug discovery.

  18. ASTEROID NAMES AND DISCOVERY V4.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes names, designations, and discovery circumstances for the numbered asteroids, sorted in order of number. This data set supercedes past versions...

  19. Astronauts Culbertson and Bursch brush their teeth on Discovery's middeck

    Science.gov (United States)

    1993-01-01

    Astronauts Frank L. Culbertson (right), mission commander, and Daniel W. Bursch, mission specialist, brush their teeth on Discovery's middeck. Two sleep restraints form part of the backdrop for the photograph.

  20. Computer-aided discovery of antimicrobial agents as potential enoyl ...

    African Journals Online (AJOL)

    Computer-aided discovery of antimicrobial agents as potential enoyl acyl carrier protein reductase inhibitors. Mohammad A Ghattas, Nermin A Eissa, Sanaa K Bardaweel, Abdallah Abu Mellal, Noor Atatreh ...