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Sample records for challenges predicting ligand-receptor

  1. Challenges predicting ligand-receptor interactions of promiscuous proteins: the nuclear receptor PXR.

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2009-12-01

    Full Text Available Transcriptional regulation of some genes involved in xenobiotic detoxification and apoptosis is performed via the human pregnane X receptor (PXR which in turn is activated by structurally diverse agonists including steroid hormones. Activation of PXR has the potential to initiate adverse effects, altering drug pharmacokinetics or perturbing physiological processes. Reliable computational prediction of PXR agonists would be valuable for pharmaceutical and toxicological research. There has been limited success with structure-based modeling approaches to predict human PXR activators. Slightly better success has been achieved with ligand-based modeling methods including quantitative structure-activity relationship (QSAR analysis, pharmacophore modeling and machine learning. In this study, we present a comprehensive analysis focused on prediction of 115 steroids for ligand binding activity towards human PXR. Six crystal structures were used as templates for docking and ligand-based modeling approaches (two-, three-, four- and five-dimensional analyses. The best success at external prediction was achieved with 5D-QSAR. Bayesian models with FCFP_6 descriptors were validated after leaving a large percentage of the dataset out and using an external test set. Docking of ligands to the PXR structure co-crystallized with hyperforin had the best statistics for this method. Sulfated steroids (which are activators were consistently predicted as non-activators while, poorly predicted steroids were docked in a reverse mode compared to 5alpha-androstan-3beta-ol. Modeling of human PXR represents a complex challenge by virtue of the large, flexible ligand-binding cavity. This study emphasizes this aspect, illustrating modest success using the largest quantitative data set to date and multiple modeling approaches.

  2. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre

    2008-01-01

    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  3. Ligand-receptor Interactions by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Novak. P.

    2008-04-01

    Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

  4. Challenges in Aircraft Noise Prediction

    OpenAIRE

    Filippone A

    2014-01-01

    This contribution addresses the problem of aircraft noise prediction using theoretical methods. The problem is set in context with the needs at several levels to produce noise characterisation from commercial aircraft powered by gas turbine engines. We describe very briefly the computational model (whilst referring the reader to the appropriate literature), and provide examples of noise predictions and comparisons with measured data, where possible. We focus on the issue of stochastic analysi...

  5. Capacity of Diffusion-based Molecular Communication with Ligand Receptors

    CERN Document Server

    Einolghozati, Arash; Fekri, Faramarz

    2012-01-01

    A diffusion-based molecular communication system has two major components: the diffusion in the medium, and the ligand-reception. Information bits, encoded in the time variations of the concentration of molecules, are conveyed to the receiver front through the molecular diffusion in the medium. The receiver, in turn, measures the concentration of the molecules in its vicinity in order to retrieve the information. This is done via ligand-reception process. In this paper, we develop models to study the constraints imposed by the concentration sensing at the receiver side and derive the maximum rate by which a ligand-receiver can receive information. Therefore, the overall capacity of the diffusion channel with the ligand receptors can be obtained by combining the results presented in this paper with our previous work on the achievable information rate of molecular communication over the diffusion channel.

  6. Inside job: ligand-receptor pharmacology beneath the plasma membrane

    Science.gov (United States)

    Babcock, Joseph J; Li, Min

    2013-01-01

    Most drugs acting on the cell surface receptors are membrane permeable and thus able to engage their target proteins in different subcellular compartments. However, these drugs' effects on cell surface receptors have historically been studied on the plasma membrane alone. Increasing evidence suggests that small molecules may also modulate their targeted receptors through membrane trafficking or organelle-localized signaling inside the cell. These additional modes of interaction have been reported for functionally diverse ligands of GPCRs, ion channels, and transporters. Such intracellular drug-target engagements affect cell surface expression. Concurrent intracellular and cell surface signaling may also increase the complexity and therapeutic opportunities of small molecule modulation. Here we discuss examples of ligand-receptor interactions that are present in both intra- and extracellular sites, and the potential therapeutic opportunities presented by this phenomenon. PMID:23685953

  7. Inside job: ligand-receptor pharmacology beneath the plasma membrane

    Institute of Scientific and Technical Information of China (English)

    Joseph J BABCOCK; Min LI

    2013-01-01

    Most drugs acting on the cell surface receptors are membrane permeable and thus able to engage their target proteins in different subcellular compartments.However,these drugs' effects on cell surface receptors have historically been studied on the plasma membrane alone.Increasing evidence suggests that small molecules may also modulate their targeted receptors through membrane trafficking or organelle-localized signaling inside the cell.These additional modes of interaction have been reported for functionally diverse ligands of GPCRs,ion channels,and transporters.Such intracellular drug-target engagements affect cell surface expression.Concurrent intracellular and cell surface signaling may also increase the complexity and therapeutic opportunities of small molecule modulation.Here we discuss examples of ligand-receptor interactions that are present in both intra- and extracellular sites,and the potential therapeutic opportunities presented by this phenomenon.

  8. Bioluminescent Ligand-Receptor Binding Assays for Protein or Peptide Hormones.

    Science.gov (United States)

    Liu, Ya-Li; Guo, Zhan-Yun

    2016-01-01

    Bioluminescence has been widely used in biomedical research due to its high sensitivity, low background, and broad linear range. In recent studies, we applied bioluminescence to ligand-receptor binding assays for some protein or peptide hormones based on a newly developed small monomeric Nanoluciferase (NanoLuc) reporter that has the so far brightest bioluminescence. The conventional ligand-receptor binding assays rely on radioligands that have drawbacks, such as radioactive hazards and short shelf lives. In contrast, the novel bioluminescent binding assays use the NanoLuc-based protein or peptide tracers that are safe, stable, and ultrasensitive. Thus, the novel bioluminescent ligand-receptor binding assay would be applied to more and more protein or peptide hormones for ligand-receptor interaction studies in future. In the present article, we provided detailed protocols for setting up the novel bioluminescent ligand-receptor binding assays using two representative protein hormones as examples. PMID:27424896

  9. Monitoring ligand-receptor interactions by photonic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Jeney, Sylvia [M E Mueller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, Basel, 4056 (Switzerland); Mor, Flavio; Forro, Laszlo [Laboratory of Complex Matter Physics (LPMC), Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland); Koszali, Roland [Institute for Information and Communication Technologies (IICT), University of Applied Sciences of Western Switzerland (HEIG-VD), Rue Galilee 15, CH 1401 Yverdon-les-bains (Switzerland); Moy, Vincent T, E-mail: sylvia.jeney@unibas.ch, E-mail: vmoy@miami.edu [Department of Physiology and Biophysics, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136 (United States)

    2010-06-25

    We introduce a method for the acquisition of single molecule force measurements of ligand-receptor interactions using the photonic force microscope (PFM). Biotin-functionalized beads, manipulated with an optical trap, and a streptavidin-functionalized coverslip were used to measure the effect of different pulling forces on the lifetime of individual streptavidin-biotin complexes. By optimizing the design of the optical trap and selection of the appropriate bead size, pulling forces in excess of 50 pN were achieved. Based on the amplitude of three-dimensional (3D) thermal position fluctuations of the attached bead, we were able to select for a bead-coverslip interaction that was mediated by a single streptavidin-biotin complex. Moreover, the developed experimental system was greatly accelerated by automation of data acquisition and analysis. In force-dependent kinetic measurements carried out between streptavidin and biotin, we observed that the streptavidin-biotin complex exhibited properties of a catch bond, with the lifetime increasing tenfold when the pulling force increased from 10 to 20 pN. We also show that silica beads were more appropriate than polystyrene beads for the force measurements, as tethers, longer than 200 nm, could be extracted from polystyrene beads.

  10. Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution

    OpenAIRE

    Park, Yoonseong; KIM, YOUNG-JOON; Adams, Michael E.

    2002-01-01

    G-protein coupled receptors (GPCRs) are ancient, ubiquitous sensors vital to environmental and physiological signaling throughout organismal life. With the publication of the Drosophila genome, numerous “orphan” GPCRs have become available for functional analysis. Here we characterize two groups of GPCRs predicted as receptors for peptides with a C-terminal amino acid sequence motif consisting of −PRXamide (PRXa). Assuming ligand-receptor coevolution, two alternative hypotheses were construct...

  11. Predicting nutrient responses in poultry: future challenges.

    Science.gov (United States)

    Gous, R M

    2007-02-01

    Predicting the response of poultry to nutrients has progressed to a stage where it is now not only possible to predict voluntary feed intake accurately, but broiler feeds and feeding programmes may now be optimised using the more advanced simulation models. Development of such prediction models has stimulated useful and purposeful research targeted at filling the gaps in our knowledge of critical aspects of the theory incorporated into these models. The aim of this paper was to review some of these past developments, discuss the controversy that exists in designing and interpreting response experiments, and highlight some of the most recent challenges related to the prediction of responses to nutrients by poultry. These latter include differences, brought about by selection for diverse goals, that have become apparent between modern broiler strains in their responses in feed intake and mortality, which are not independent of level of feeding or strain of broiler, as was previously believed. Uniformity, an important quality criterion in broiler processing, is also not independent of level of feeding, and the effect may now be predicted using stochastic models. It is not yet clear whether breast meat yield, the carcass component of broilers yielding the highest returns, is a function of the strain of broiler or simply that of the protein weight of the bird when processed. An important aspect of response prediction is dealing with constraints to performance: whereas it is relatively straightforward to simulate the potential performance of a broiler, such performance is often constrained by the physical, social and infectious environment, among others, providing a challenge to modellers attempting to predict actual performance. Some of these constraints to potential performance have not yet been adequately described, but are now receiving attention, suggesting that nutrient responses in poultry have the potential to be more accurately predicted in the future. PMID

  12. Functional phylogenetics reveals contributions of pleiotropic peptide action to ligand-receptor coevolution

    Science.gov (United States)

    The evolution of peptidergic signaling has been accompanied by a significant degree of ligand-receptor coevolution. Closely related clusters of peptide signaling molecules are observed to activate related groups of receptors, implying that genes encoding these ligands may orchestrate an array of fu...

  13. Unnatural amino acids as probes of ligand-receptor interactions and their conformational consequences

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Ahern, Christopher A

    2013-01-01

    -edge synthetic and chemical biological approaches. Here we summarize recent advances in the use of site-directed incorporation of unnatural amino acids and chemical probes to study ligand-receptor interactions, determine the location of binding sites, and examine the downstream conformational consequences of...

  14. Sliding tethered ligands add topological interactions to the toolbox of ligand-receptor design

    Science.gov (United States)

    Bauer, Martin; Kékicheff, Patrick; Iss, Jean; Fajolles, Christophe; Charitat, Thierry; Daillant, Jean; Marques, Carlos M.

    2015-09-01

    Adhesion in the biological realm is mediated by specific lock-and-key interactions between ligand-receptor pairs. These complementary moieties are ubiquitously anchored to substrates by tethers that control the interaction range and the mobility of the ligands and receptors, thus tuning the kinetics and strength of the binding events. Here we add sliding anchoring to the toolbox of ligand-receptor design by developing a family of tethered ligands for which the spacer can slide at the anchoring point. Our results show that this additional sliding degree of freedom changes the nature of the adhesive contact by extending the spatial range over which binding may sustain a significant force. By introducing sliding tethered ligands with self-regulating length, this work paves the way for the development of versatile and reusable bio-adhesive substrates with potential applications for drug delivery and tissue engineering.

  15. The evolution of the ligand/receptor couple: a long road from comparative endocrinology to comparative genomics

    OpenAIRE

    Markov, Gabriel V.; Paris, Mathilde; Bertrand, Stephanie; Laudet, Vincent

    2008-01-01

    The evolution of the ligand/receptor couple: a long road from comparative endocrinology to comparative genomics FRANCE (Markov, Gabriel V.) FRANCE Received: 2008-02-11 Revised: 2008-05-14 Accepted: 2008-06-11

  16. Yelp Dataset Challenge: Review Rating Prediction

    OpenAIRE

    Asghar, Nabiha

    2016-01-01

    Review websites, such as TripAdvisor and Yelp, allow users to post online reviews for various businesses, products and services, and have been recently shown to have a significant influence on consumer shopping behaviour. An online review typically consists of free-form text and a star rating out of 5. The problem of predicting a user's star rating for a product, given the user's text review for that product, is called Review Rating Prediction and has lately become a popular, albeit hard, pro...

  17. CLE Peptides in Plants: Proteolytic Processing,Structure-Activity Relationship, and Ligand-Receptor Interaction

    Institute of Scientific and Technical Information of China (English)

    Xiaoming Gao; Yongfeng Guo

    2012-01-01

    Ligand-receptor signaling initiated by the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) family peptides is critical in regulating cell division and differentiation in meristematic tissues in plants.Biologically active CLE peptides are released from precursor proteins via proteolytic processing.The mature form of CLE ligands consists of 12-13 amino acids with several post-translational modifications.This review summarizes recent progress toward understanding the proteolytic activities that cleave precursor proteins to release CLE peptides,the molecular structure and function of mature CLE ligands,and interactions between CLE ligands and corresponding leucine-rich repeat (LRR) receptor-like kinases (RLKs).

  18. Lipid domain formation and ligand-receptor distribution in lipid bilayer membranes investigated by atomic force microscopy

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Mouritsen, O.G.; Jørgensen, K.

    A novel experimental technique, based on atomic force microscopy (AFM), is proposed to visualize the lateral organization of membrane systems in the nanometer range. The technique involves the use of a ligand-receptor pair, biotin-avidin, which introduces a height variation on a solid-supported l......A novel experimental technique, based on atomic force microscopy (AFM), is proposed to visualize the lateral organization of membrane systems in the nanometer range. The technique involves the use of a ligand-receptor pair, biotin-avidin, which introduces a height variation on a solid...

  19. Large Hadron Collider (LHC) phenomenology, operational challenges and theoretical predictions

    CERN Document Server

    Gilles, Abelin R

    2013-01-01

    The Large Hadron Collider (LHC) is the highest-energy particle collider ever constructed and is considered "one of the great engineering milestones of mankind." It was built by the European Organization for Nuclear Research (CERN) from 1998 to 2008, with the aim of allowing physicists to test the predictions of different theories of particle physics and high-energy physics, and particularly prove or disprove the existence of the theorized Higgs boson and of the large family of new particles predicted by supersymmetric theories. In this book, the authors study the phenomenology, operational challenges and theoretical predictions of LHC. Topics discussed include neutral and charged black hole remnants at the LHC; the modified statistics approach for the thermodynamical model of multiparticle production; and astroparticle physics and cosmology in the LHC era.

  20. Feedback, receptor clustering, and receptor restriction to single cells yield large Turing spaces for ligand-receptor-based Turing models

    Science.gov (United States)

    Kurics, Tamás; Menshykau, Denis; Iber, Dagmar

    2014-08-01

    Turing mechanisms can yield a large variety of patterns from noisy, homogenous initial conditions and have been proposed as patterning mechanism for many developmental processes. However, the molecular components that give rise to Turing patterns have remained elusive, and the small size of the parameter space that permits Turing patterns to emerge makes it difficult to explain how Turing patterns could evolve. We have recently shown that Turing patterns can be obtained with a single ligand if the ligand-receptor interaction is taken into account. Here we show that the general properties of ligand-receptor systems result in very large Turing spaces. Thus, the restriction of receptors to single cells, negative feedbacks, regulatory interactions among different ligand-receptor systems, and the clustering of receptors on the cell surface all greatly enlarge the Turing space. We further show that the feedbacks that occur in the FGF10-SHH network that controls lung branching morphogenesis are sufficient to result in large Turing spaces. We conclude that the cellular restriction of receptors provides a mechanism to sufficiently increase the size of the Turing space to make the evolution of Turing patterns likely. Additional feedbacks may then have further enlarged the Turing space. Given their robustness and flexibility, we propose that receptor-ligand-based Turing mechanisms present a general mechanism for patterning in biology.

  1. Dual-point competition association assay: a fast and high-throughput kinetic screening method for assessing ligand-receptor binding kinetics.

    Science.gov (United States)

    Guo, Dong; van Dorp, Erika J H; Mulder-Krieger, Thea; van Veldhoven, Jacobus P D; Brussee, Johannes; Ijzerman, Adriaan P; Heitman, Laura H

    2013-03-01

    The concept of ligand-receptor binding kinetics is emerging as an important parameter in the early phase of drug discovery. Since the currently used kinetic assays are laborious and low throughput, we developed a method that enables fast and large format screening. It is a so-called dual-point competition association assay, which measures radioligand binding at two different time points in the absence or presence of unlabeled competitors. Specifically, this assay yields the kinetic rate index (KRI), which is a measure for the binding kinetics of the unlabeled ligands screened. As a prototypical drug target, the adenosine A(1) receptor (A(1)R) was chosen for assay validation and optimization. A screen with 35 high-affinity A(1)R antagonists yielded seven compounds with a KRI value above 1.0, which indicated a relatively slow dissociation from the target. All other compounds had a KRI value below or equal to 1.0, predicting a relatively fast dissociation rate. Several compounds were selected for follow-up kinetic quantifications in classical kinetic assays and were shown to have kinetic rates that corresponded to their KRI values. The dual-point assay and KRI value may have general applicability at other G-protein-coupled receptors, as well as at drug targets from other protein families. PMID:23093571

  2. Application of the novel bioluminescent ligand-receptor binding assay to relaxin-RXFP1 system for interaction studies.

    Science.gov (United States)

    Wu, Qing-Ping; Zhang, Lei; Shao, Xiao-Xia; Wang, Jia-Hui; Gao, Yu; Xu, Zeng-Guang; Liu, Ya-Li; Guo, Zhan-Yun

    2016-04-01

    Relaxin is a prototype of the relaxin family peptide hormones and plays important biological functions by binding and activating the G protein-coupled receptor RXFP1. To study their interactions, in the present work, we applied the newly developed bioluminescent ligand-receptor binding assay to the relaxin-RXFP1 system. First, a fully active easily labeled relaxin, in which three Lys residues of human relaxin-2 were replaced by Arg, was prepared through overexpression of a single-chain precursor in Pichia pastoris and in vitro enzymatic maturation. Thereafter, the B-chain N-terminus of the easily labeled relaxin was chemically cross-linked with a C-terminal cysteine residue of an engineered NanoLuc through a disulfide linkage. Receptor-binding assays demonstrated that the NanoLuc-conjugated relaxin retained high binding affinity with the receptor RXFP1 (K d = 1.11 ± 0.08 nM, n = 3) and was able to sensitively monitor binding of a variety of ligands with RXFP1. Using the novel bioluminescent binding assay, we demonstrated that three highly conserved B-chain Arg residues of relaxin-3 had distinct contributions to binding of the receptor RXFP1. In summary, our present work provides a novel bioluminescent ligand-receptor binding assay for the relaxin-RXFP1 system to facilitate their interaction studies, such as characterization of relaxin analogues or screening novel agonists or antagonists of RXFP1. PMID:26767372

  3. Challenges in Lagrangian transport and predictability in 3D flows

    Science.gov (United States)

    Branicki, M.; Wiggins, S.; Kirwan, A. D.; Malek-Madani, R.

    2011-12-01

    The interplay between the geometrical theory of dynamical systems and the trajectory-based description of aperiodically time-dependent fluid flows has led to significant advances in understanding the role of chaotic transport in geophysical flows at scales dominated by advection. Lagrangian transport analysis utilizing either the time-dependent geometry of intersecting stable and unstable manifolds of the so-called Distinguished Hyperbolic Trajectories (DHT), or ridges of finite-time Lyapunov exponent fields (LCS), provide a much needed and complementary insight into ephemeral mechanisms responsible for the existence of `leaky' transport barriers and 'leaky' mesoscale eddies. However, to date most oceanic applications have been confined to 2D analysis of near surface regions in 'perfect' flows not accounting for model or measurement error, and with the tacit assumption of negligible vertical velocities. I will systematically address issues concerning the regimes of applicability of two-dimensional analysis in 3D aperiodically time-dependent flows, as well as outstanding challenges in fully 3D Lagrangian transport analysis. Even for perfect horizontal velocities, little is known about the vertical extent of stable/unstable manifolds associated with DHTs and/or other special structures relevant to stratified 3D flows. In particular, their sensitivity to errors in the vertical velocities and data assimilation methods has been little studied. Rigorous results regarding the above issues will be illustrated by revealing and mathematically tractable toy models, as well as examples from a detailed study in an eddy-rich region from the Gulf of Mexico and the Mediterranean. New ways of quantifying the uncertainty in Lagrangian predictions will also be presented.

  4. Wildfire Prediction to Inform Fire Management: Statistical Science Challenges

    CERN Document Server

    Taylor, S W; Dean, C B; Martell, David L

    2013-01-01

    Wildfire is an important system process of the earth that occurs across a wide range of spatial and temporal scales. A variety of methods have been used to predict wildfire phenomena during the past century to better our understanding of fire processes and to inform fire and land management decision-making. Statistical methods have an important role in wildfire prediction due to the inherent stochastic nature of fire phenomena at all scales. Predictive models have exploited several sources of data describing fire phenomena. Experimental data are scarce; observational data are dominated by statistics compiled by government fire management agencies, primarily for administrative purposes and increasingly from remote sensing observations. Fires are rare events at many scales. The data describing fire phenomena can be zero-heavy and nonstationary over both space and time. Users of fire modeling methodologies are mainly fire management agencies often working under great time constraints, thus, complex models have t...

  5. Stamping Vital Cells—a Force-Based Ligand Receptor Assay

    OpenAIRE

    Wienken, Uta; Gaub, Hermann E.

    2013-01-01

    Gaining information about receptor profiles on cells, and subsequently finding the most efficient ligands for these signaling receptors, remain challenging tasks in stem cell and cancer research as well as drug development. We introduce a live-cell method with great potential in both screening for surface receptors and analysing binding forces of different ligands. The technique is based on the molecular force assay, a parallel-format, high-throughput experiment on a single-molecule level. On...

  6. Prediction Models and Decision Support: Chances and Challenges

    OpenAIRE

    Kappen, T.H.

    2015-01-01

    A clinical prediction model can assist doctors in arriving at the most likely diagnosis or estimating the prognosis. By utilizing various patient- and disease-related properties, such models can yield objective estimations of the risk of a disease or the probability of a certain disease course for individual patients. Doctors can then use this individual probability in their decision making process, thereby (hopefully) improving patient outcome. However, even when its probability estimates ar...

  7. Predictive models for nanotoxicology: current challenges and future opportunities.

    OpenAIRE

    Clark Katherine A.; White Ronald H.; Silbergeld Ellen K

    2011-01-01

    Characterizing the risks posed by nanomaterials is extraordinarily complex because these materials can have a wide range of sizes, shapes, chemical compositions and surface modifications, all of which may affect toxicity. There is an urgent need for a testing strategy that can rapidly and efficiently provide a screening approach for evaluating the potential hazard of nanomaterials and inform the prioritization of additional toxicological testing where necessary. Predictive toxicity models cou...

  8. The Challenge of Predicting the Occurrence of Intense Storms

    Indian Academy of Sciences (India)

    Nandita Srivastava

    2006-06-01

    Geomagnetic super-storms of October and November 2003 are compared in order to identify solar and interplanetary variables that influence the magnitude of geomagnetic storms. Although these super-storms (DST < -300 nT) are associated with high speed CMEs, their DST indices show large variation. The most intense storm of November 20, 2003 (DST ∼ -472 nT) had its source in a comparatively small active region and was associated with a relatively weaker, M-class flare, while the others had their origins in large active regions and were associated with strong X-class flares. An attempt has been made to implement a logistic regression model for the prediction of the occurrence of intense/super-intense geomagnetic storms. The model parameters (regression coefficients) were estimated from a training data-set extracted from a data-set of 64 geo-effective CMEs observed during 1996–2002. The results indicate that logistic regression models can be effectively used for predicting the occurrence of major geomagnetic storms from a set of solar and interplanetary factors. The model validation shows that 100% of the intense storms (-200 nT < DST < -100 nT) and only 50% of the super-intense (DST < -200 nT) storms could be correctly predicted.

  9. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Monine, Michael [Los Alamos National Laboratory; Posner, Richard [TRANSLATION GENOMICS RESAEARCH INSTITUTE; Savage, Paul [BYU; Faeder, James [UNIV OF PITTSBURGH; Hlavacek, William S [UNM

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  10. Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

    Science.gov (United States)

    Liang, Junshi; Chen, Pengyu; Dong, Bojun; Huang, Zihan; Zhao, Kongyin; Yan, Li-Tang

    2016-05-01

    Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications. PMID:27049403

  11. Challenges, basic principles and methodologies for decadal predictability and forecasts

    International Nuclear Information System (INIS)

    Within the framework of the 5. coupled model inter-comparison project, an ensemble of coordinated decadal forecast simulations have been carried out, for the first time, by the climate community. This new initiative first aims at better understanding the decadal modulations that are superimposed on the anthropogenic-forced warming tendency and that are mostly explained, at such a timescale, by the internal variability in the ocean. The goal of this initiative is then to provide a first assessment of the climate predictability at decadal timescale. Forecasts differ from climate projections by the mandatory step of initialization of the model components either to direct observations or their reconstruction via the reanalyzes. They aim at simulating at best the observed fluctuations whereas projections and historical simulations only estimate the climate response to so-called external forcings such as solar activity, volcanism and anthropogenic perturbations. The goal of this article is primarily to review the basics of the decadal forecasts (concepts, methodologies, difficulties and limits) and to present preliminary and simple results on predictive skill estimated from hind-casts over 1960-2010. (authors)

  12. Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles

    OpenAIRE

    Gibon, Emmanuel; Ma, Ting; Ren, Pei-Gen; Fritton, Kate; Biswal, Sandip; Yao, Zhenyu; Smith, Lane; Goodman, Stuart B.

    2011-01-01

    The biological mechanisms leading to periprosthetic osteolysis involve both chemokines and the monocyte/macrophage cell lineage. Whether MCP-1 plays a major role in macrophage recruitment in the presence of wear particles is unknown. We tested two hypotheses: (1) that exogenous local delivery of MCP-1 induces systematic macrophage recruitment and (2) that blockade of the MCP-1 ligand-receptor axis decreases macrophage recruitment and osteolysis in the presence of UHMWPE particles. Six groups ...

  13. WScore: A Flexible and Accurate Treatment of Explicit Water Molecules in Ligand-Receptor Docking.

    Science.gov (United States)

    Murphy, Robert B; Repasky, Matthew P; Greenwood, Jeremy R; Tubert-Brohman, Ivan; Jerome, Steven; Annabhimoju, Ramakrishna; Boyles, Nicholas A; Schmitz, Christopher D; Abel, Robert; Farid, Ramy; Friesner, Richard A

    2016-05-12

    We have developed a new methodology for protein-ligand docking and scoring, WScore, incorporating a flexible description of explicit water molecules. The locations and thermodynamics of the waters are derived from a WaterMap molecular dynamics simulation. The water structure is employed to provide an atomic level description of ligand and protein desolvation. WScore also contains a detailed model for localized ligand and protein strain energy and integrates an MM-GBSA scoring component with these terms to assess delocalized strain of the complex. Ensemble docking is used to take into account induced fit effects on the receptor conformation, and protein reorganization free energies are assigned via fitting to experimental data. The performance of the method is evaluated for pose prediction, rank ordering of self-docked complexes, and enrichment in virtual screening, using a large data set of PDB complexes and compared with the Glide SP and Glide XP models; significant improvements are obtained. PMID:27054459

  14. Energetics of ligand-receptor binding affinity on endothelial cells: An in vitro model.

    Science.gov (United States)

    Fotticchia, Iolanda; Guarnieri, Daniela; Fotticchia, Teresa; Falanga, Andrea Patrizia; Vecchione, Raffaele; Giancola, Concetta; Netti, Paolo Antonio

    2016-08-01

    Targeted therapies represent a challenge in modern medicine. In this contest, we propose a rapid and reliable methodology based on Isothermal Titration Calorimetry (ITC) coupled with confluent cell layers cultured around biocompatible templating microparticles to quantify the number of overexpressing receptors on cell membrane and study the energetics of receptor-ligand binding in near-physiological conditions. In the in vitro model here proposed we used the bEnd3 cell line as brain endothelial cells to mimic the blood brain barrier (BBB) cultured on dextran microbeads ranging from 67μm to 80μm in size (Cytodex) and the primary human umbilical vein cells (HUVEC) for comparison. The revealed affinity between transferrin (Tf) and transferrin receptor (TfR) in both systems is very high, Kd values are in the order of nM. Conversely, the value of TfRs/cell reveals a 100-fold increase in the number of TfRs per bEnd3 cells compared to HUVEC cells. The presented methodology can represent a novel and helpful strategy to identify targets, to address drug design and selectively deliver therapeutics that can cross biological barriers such as the blood brain barrier. PMID:27100851

  15. The predictive value of bronchial histamine challenge in the diagnosis of bronchial asthma

    DEFF Research Database (Denmark)

    Madsen, F; Holstein-Rathlou, N H; Mosbech, H;

    1985-01-01

    A prospective survey aiming to study the predictive value of bronchial histamine challenge was performed on 151 patients with a forced expiratory volume1 (FEV1) above 60% of predicted. According to variations in peak expiratory flow rate (PEFR) and medical history the patients were classified as...... below 0.125 mg/ml the predictive value of a positive test was 1.00, but an increase in PC20 in the range from 4.00 to 16 mg/ml did not increase the predictive value of a negative test. In this study the prevalence of asthma was about 0.6. We therefore conclude that bronchial histamine challenge is a...... valuable test for detection and exclusion of bronchial asthma, when the prevalence of the disease is high. In populations with a lower frequency of bronchial asthma the diagnostic value of a positive bronchial challenge will be negligible....

  16. Applying predictive clustering trees to the inductive logic programming 2005 challenge data

    OpenAIRE

    Struyf, Jan; Vens, Celine; Croonenborghs, Tom; Džeroski, Sašo; Blockeel, Hendrik

    2005-01-01

    This paper presents our submission to the Inductive Logic Programming 2005 Challenge. The goal of this challenge is to build accurate models predicting gene function in the genome of the yeast Saccharomyces cerevisiae based on relational homology and secondary structure data. The approach that we follow consists of two steps. In the first step, the data is propositionalized by constructing features with the relational frequent pattern mining system WARMR (relational features including aggrega...

  17. The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis.

    Science.gov (United States)

    Duncan, Rony E; Gillam, Lynn; Savulescu, Julian; Williamson, Robert; Rogers, John G; Delatycki, Martin B

    2010-03-01

    Predictive genetic tests for familial adenomatous polyposis (FAP) are routinely offered to young people during early adolescence. While this is not controversial, due to the medical benefit conferred by the test, it is nonetheless challenging as a consequence of the stage of life of the young people, and the simultaneous involvement of multiple family members. Despite these challenges, it is possible to ensure that the test is offered in such a way that it actively acknowledges and facilitates young people's developing autonomy and psychosocial well-being. In this paper we present findings from ten in-depth interviews with young people who have undergone predictive genetic testing for FAP (four male, six female; five gene-positive, five gene-negative; aged 10-17 years at the time of their predictive test; aged 12-25 years at the time of their research interview). We present five themes that emerged from the interviews which highlight key ethical challenges associated with such testing. These are: (1) the significance of the test; (2) young people's lack of involvement in the decision to be tested; (3) young people's limited understanding; (4) provision of the blood test at the first visit; and (5) group testing of family members. We draw on these themes to make eight recommendations for future practice. Together, these recommendations highlight the importance of providing developmentally appropriate care to young people undergoing predictive genetic testing for FAP. PMID:19760114

  18. Toward a Predictive Understanding of Earth’s Microbiomes to Address 21st Century Challenges

    Science.gov (United States)

    Blaser, Martin J.; Cardon, Zoe G.; Cho, Mildred K.; Dangl, Jeffrey L.; Green, Jessica L.; Knight, Rob; Maxon, Mary E.; Northen, Trent R.; Pollard, Katherine S.

    2016-01-01

    ABSTRACT Microorganisms have shaped our planet and its inhabitants for over 3.5 billion years. Humankind has had a profound influence on the biosphere, manifested as global climate and land use changes, and extensive urbanization in response to a growing population. The challenges we face to supply food, energy, and clean water while maintaining and improving the health of our population and ecosystems are significant. Given the extensive influence of microorganisms across our biosphere, we propose that a coordinated, cross-disciplinary effort is required to understand, predict, and harness microbiome function. From the parallelization of gene function testing to precision manipulation of genes, communities, and model ecosystems and development of novel analytical and simulation approaches, we outline strategies to move microbiome research into an era of causality. These efforts will improve prediction of ecosystem response and enable the development of new, responsible, microbiome-based solutions to significant challenges of our time. PMID:27178263

  19. Toward a Predictive Understanding of Earth's Microbiomes to Address 21st Century Challenges.

    Science.gov (United States)

    Blaser, Martin J; Cardon, Zoe G; Cho, Mildred K; Dangl, Jeffrey L; Donohue, Timothy J; Green, Jessica L; Knight, Rob; Maxon, Mary E; Northen, Trent R; Pollard, Katherine S; Brodie, Eoin L

    2016-01-01

    Microorganisms have shaped our planet and its inhabitants for over 3.5 billion years. Humankind has had a profound influence on the biosphere, manifested as global climate and land use changes, and extensive urbanization in response to a growing population. The challenges we face to supply food, energy, and clean water while maintaining and improving the health of our population and ecosystems are significant. Given the extensive influence of microorganisms across our biosphere, we propose that a coordinated, cross-disciplinary effort is required to understand, predict, and harness microbiome function. From the parallelization of gene function testing to precision manipulation of genes, communities, and model ecosystems and development of novel analytical and simulation approaches, we outline strategies to move microbiome research into an era of causality. These efforts will improve prediction of ecosystem response and enable the development of new, responsible, microbiome-based solutions to significant challenges of our time. PMID:27178263

  20. Predictions for the Future World of Work: Challenges for Information Professionals

    OpenAIRE

    Ashcroft, Linda

    2008-01-01

    There are challenges for the new information professional. In recent years technological development and changes in the quantity of and access to information has influenced the nature of information work. Predictions for the future include the ‘cybrarian’. Yet various studies demonstrate the continuing need for a physical place which plays a vital role in the informal gathering of community members. While traditional library support functions may continue, there are many changes to the natur...

  1. Software Design Challenges in Time Series Prediction Systems Using Parallel Implementation of Artificial Neural Networks

    OpenAIRE

    Narayanan Manikandan; Srinivasan Subha

    2016-01-01

    Software development life cycle has been characterized by destructive disconnects between activities like planning, analysis, design, and programming. Particularly software developed with prediction based results is always a big challenge for designers. Time series data forecasting like currency exchange, stock prices, and weather report are some of the areas where an extensive research is going on for the last three decades. In the initial days, the problems with financial analysis and predi...

  2. Attracted to power: Challenge / threat and promotion / prevention focus differentially predict the attractiveness of group power

    Directory of Open Access Journals (Sweden)

    Annika eScholl

    2015-04-01

    Full Text Available Depending on their motivation, individuals prefer different group contexts for social interactions. The present research sought to provide more insight into this relationship. More specifically, we tested how challenge / threat and a promotion / prevention focus predict attraction to groups with high or low power. As such, we examined differential outcomes of threat and prevention focus as well as challenge and promotion focus that have often been regarded as closely related. According to regulatory focus, individuals should prefer groups that they expect to feel right for them to join: Low-power groups should be more attractive in a prevention (than a promotion focus, as these groups suggest security-oriented strategies, which fit a prevention focus. High-power groups should be more attractive in a promotion (rather than a prevention focus, as these groups are associated with promotion strategies fitting a promotion focus (Sassenberg, Jonas, Shah, & Brazy, 2007. In contrast, under threat (vs. challenge, groups that allow individuals to restore their (perceived lack of control should be preferred: Low-power groups should be less attractive under threat (than challenge because they provide low resources which threatened individuals already perceive as insufficient and high-power groups might be more attractive under threat (than under challenge, because their high resources allow individuals to restore control. Two experiments (N = 140 supported these predictions. The attractiveness of a group often depends on the motivation to engage in what fits (i.e., prefer a group that feels right in the light of one’s regulatory focus. However, under threat the striving to restore control (i.e., prefer a group allowing them to change the statuts quo under threat vs. challenge overrides the fit effect, which may in turn guide individuals’ behavior in social interactions.

  3. Challenges in Real-Time Prediction of Infectious Disease: A Case Study of Dengue in Thailand.

    Science.gov (United States)

    Reich, Nicholas G; Lauer, Stephen A; Sakrejda, Krzysztof; Iamsirithaworn, Sopon; Hinjoy, Soawapak; Suangtho, Paphanij; Suthachana, Suthanun; Clapham, Hannah E; Salje, Henrik; Cummings, Derek A T; Lessler, Justin

    2016-06-01

    Epidemics of communicable diseases place a huge burden on public health infrastructures across the world. Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks. However, scientists and public health officials face many obstacles in trying to create such real-time forecasts of infectious disease incidence. Dengue is a mosquito-borne virus that annually infects over 400 million people worldwide. We developed a real-time forecasting model for dengue hemorrhagic fever in the 77 provinces of Thailand. We created a practical computational infrastructure that generated multi-step predictions of dengue incidence in Thai provinces every two weeks throughout 2014. These predictions show mixed performance across provinces, out-performing seasonal baseline models in over half of provinces at a 1.5 month horizon. Additionally, to assess the degree to which delays in case reporting make long-range prediction a challenging task, we compared the performance of our real-time predictions with predictions made with fully reported data. This paper provides valuable lessons for the implementation of real-time predictions in the context of public health decision making. PMID:27304062

  4. Software Design Challenges in Time Series Prediction Systems Using Parallel Implementation of Artificial Neural Networks

    Science.gov (United States)

    Manikandan, Narayanan; Subha, Srinivasan

    2016-01-01

    Software development life cycle has been characterized by destructive disconnects between activities like planning, analysis, design, and programming. Particularly software developed with prediction based results is always a big challenge for designers. Time series data forecasting like currency exchange, stock prices, and weather report are some of the areas where an extensive research is going on for the last three decades. In the initial days, the problems with financial analysis and prediction were solved by statistical models and methods. For the last two decades, a large number of Artificial Neural Networks based learning models have been proposed to solve the problems of financial data and get accurate results in prediction of the future trends and prices. This paper addressed some architectural design related issues for performance improvement through vectorising the strengths of multivariate econometric time series models and Artificial Neural Networks. It provides an adaptive approach for predicting exchange rates and it can be called hybrid methodology for predicting exchange rates. This framework is tested for finding the accuracy and performance of parallel algorithms used. PMID:26881271

  5. Software Design Challenges in Time Series Prediction Systems Using Parallel Implementation of Artificial Neural Networks.

    Science.gov (United States)

    Manikandan, Narayanan; Subha, Srinivasan

    2016-01-01

    Software development life cycle has been characterized by destructive disconnects between activities like planning, analysis, design, and programming. Particularly software developed with prediction based results is always a big challenge for designers. Time series data forecasting like currency exchange, stock prices, and weather report are some of the areas where an extensive research is going on for the last three decades. In the initial days, the problems with financial analysis and prediction were solved by statistical models and methods. For the last two decades, a large number of Artificial Neural Networks based learning models have been proposed to solve the problems of financial data and get accurate results in prediction of the future trends and prices. This paper addressed some architectural design related issues for performance improvement through vectorising the strengths of multivariate econometric time series models and Artificial Neural Networks. It provides an adaptive approach for predicting exchange rates and it can be called hybrid methodology for predicting exchange rates. This framework is tested for finding the accuracy and performance of parallel algorithms used. PMID:26881271

  6. Software Design Challenges in Time Series Prediction Systems Using Parallel Implementation of Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Narayanan Manikandan

    2016-01-01

    Full Text Available Software development life cycle has been characterized by destructive disconnects between activities like planning, analysis, design, and programming. Particularly software developed with prediction based results is always a big challenge for designers. Time series data forecasting like currency exchange, stock prices, and weather report are some of the areas where an extensive research is going on for the last three decades. In the initial days, the problems with financial analysis and prediction were solved by statistical models and methods. For the last two decades, a large number of Artificial Neural Networks based learning models have been proposed to solve the problems of financial data and get accurate results in prediction of the future trends and prices. This paper addressed some architectural design related issues for performance improvement through vectorising the strengths of multivariate econometric time series models and Artificial Neural Networks. It provides an adaptive approach for predicting exchange rates and it can be called hybrid methodology for predicting exchange rates. This framework is tested for finding the accuracy and performance of parallel algorithms used.

  7. Typology of Hydrologic Prediction Challenges and Implications for Trustworthy Model Development

    Science.gov (United States)

    Kumar, P.

    2011-12-01

    Traditional classification of predictability challenges are based under the assumption of a static landscape that doesn't change under the influence of the dynamics it supports. Further, it is largely targeted to address the problem of predicting an observed trajectory. Characterizing the behavioral space of possible outcomes, possibly leading to the discovery of new phenomenon is an important dual problem. This problem is particularly relevant for situations where landscape organization is subject to change either in response to slow modes of the dynamics or due to exogenous factors such as human impact or environmental change. Under these circumstances, new connectivity patterns may arise leading to ephemeral or persistent new interactions. The connectivity patterns enslave the short-term dynamics typically resulting in threshold type responses and alternate dynamic regimes. The problem of representing the co-evolution of systems with vastly different time scales of feedbacks is an open challenging problem. However, this is the type of interaction that leads to non-stationary as well as catastrophic responses. Given this categorization, new challenges emerge for formulating a suitable model diagnostics that attempts to find those components of the model that can explain the observed discrepancy between observation and prediction. For appropriate attribution, the model diagnostics need to consider prediction errors in conjunction with the model structure error arising from the attributes for facilitating emergent connectivity patterns and co-evolutionary dynamics across space and time scales involving a hierarchy of processes representations. This requires novelty in defining predictable structure(s) in a model's behavioral space and developing quantitative methodologies for detection and attribution. New observational and interpretation framework may need to be devised to disentangle the fast and slow dynamics and their coupled behavior so that suitable framework

  8. Challenges of using model predictive control for active demand side management

    DEFF Research Database (Denmark)

    Zong, Yi; You, Shi; Hu, Junjie;

    2015-01-01

    When there is a high penetration of renewables in the power system, it requires coordinated management of large numbers of distributed and demand response resources, intermittent resources to maintain the grid reliability and improve operational economics. This paper presents a hierarchical...... architecture design for Model Predictive Controller (MPC), and discusses the challenges encountered during the implementation of MPC for active demand side management. The two different pilot case studies show that energy savings and load shifting can be achieved by applying MPC with weather forecast and...

  9. The missing link: delayed emotional development predicts challenging behavior in adults with intellectual disability.

    Science.gov (United States)

    Sappok, Tanja; Budczies, Jan; Dziobek, Isabel; Bölte, Sven; Dosen, Anton; Diefenbacher, Albert

    2014-04-01

    Individuals with intellectual disability (ID) show high rates of challenging behavior (CB). The aim of this retrospective study was to assess the factors underlying CB in an adult, clinical ID sample (n = 203). Low levels of emotional development (ED), as measured by the Scheme of Appraisal of ED, predicted overall CB, specifically irritability and self-injury, high unemployment and low occupation rates, while severity of ID controlled for ED did not. Autism was the only mental disorder associated with overall CB, stereotypy, lethargy, and predicted antipsychotic drug usage. Given the persistence and clinical significance of CB, evaluation of autism and ED may suggest priority areas for diagnostics and therapy, to provide the prerequisites for participation in society and living up one's potentials. PMID:24002416

  10. Consensus Statement on Electronic Health Predictive Analytics: A Guiding Framework to Address Challenges

    Science.gov (United States)

    Amarasingham, Ruben; Audet, Anne-Marie J.; Bates, David W.; Glenn Cohen, I.; Entwistle, Martin; Escobar, G. J.; Liu, Vincent; Etheredge, Lynn; Lo, Bernard; Ohno-Machado, Lucila; Ram, Sudha; Saria, Suchi; Schilling, Lisa M.; Shahi, Anand; Stewart, Walter F.; Steyerberg, Ewout W.; Xie, Bin

    2016-01-01

    Context: The recent explosion in available electronic health record (EHR) data is motivating a rapid expansion of electronic health care predictive analytic (e-HPA) applications, defined as the use of electronic algorithms that forecast clinical events in real time with the intent to improve patient outcomes and reduce costs. There is an urgent need for a systematic framework to guide the development and application of e-HPA to ensure that the field develops in a scientifically sound, ethical, and efficient manner. Objectives: Building upon earlier frameworks of model development and utilization, we identify the emerging opportunities and challenges of e-HPA, propose a framework that enables us to realize these opportunities, address these challenges, and motivate e-HPA stakeholders to both adopt and continuously refine the framework as the applications of e-HPA emerge. Methods: To achieve these objectives, 17 experts with diverse expertise including methodology, ethics, legal, regulation, and health care delivery systems were assembled to identify emerging opportunities and challenges of e-HPA and to propose a framework to guide the development and application of e-HPA. Findings: The framework proposed by the panel includes three key domains where e-HPA differs qualitatively from earlier generations of models and algorithms (Data Barriers, Transparency, and Ethics) and areas where current frameworks are insufficient to address the emerging opportunities and challenges of e-HPA (Regulation and Certification; and Education and Training). The following list of recommendations summarizes the key points of the framework: Data Barriers: Establish mechanisms within the scientific community to support data sharing for predictive model development and testing.Transparency: Set standards around e-HPA validation based on principles of scientific transparency and reproducibility.Ethics: Develop both individual-centered and society-centered risk-benefit approaches to evaluate

  11. Prediction of cerebral hyperperfusion syndrome after carotid artery stenting by CT perfusion imaging with acetazolamide challenge

    Energy Technology Data Exchange (ETDEWEB)

    Yoshie, Tomohide; Ueda, Toshihiro; Takada, Tatsuro; Nogoshi, Shinji; Fukano, Takayuki [St. Marianna University Toyoko Hospital, Department of Strokology, Stroke Center, Kawasaki (Japan); Hasegawa, Yasuhiro [St. Marianna University School of Medicine, Department of Internal Medicine, Division of Neurology, Kawasaki (Japan)

    2016-03-15

    Cerebral hyperperfusion syndrome (HPS) is an uncommon but serious complication of carotid artery stenting (CAS). The purpose of this study was to investigate the efficacy of CT perfusion imaging (CTP) with acetazolamide challenge to identify patients at risk for HPS after CAS. We retrospectively analyzed 113 patients who underwent CTP with rest and acetazolamide challenge before CAS. CTP maps were assessed for absolute and relative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and change of each parameter before and after acetazolamide challenge. Patients were divided into two groups according to the HPS after the CAS. Receiver-operating characteristic (ROC) curve analysis was performed to determine the most accurate CTP parameter for the prediction of HPS. Nine of 113 patients had HPS. There were significant differences for absolute and relative values of resting CBF (p = 0.001 and p = 0.026), resting MTT (p < 0.001 and p = 0.004), post-acetazolamide CBF (p < 0.001 and p = 0.001), post-acetazolamide MTT (p < 0.001 and p = 0.002), and %changes of CBF (p = 0.009) between the HPS and non-HPS groups. ROC curve analysis showed that the CTP parameters with the maximal area under the receiver-operating characteristic curve (AUC) for HPS was the absolute value of post-acetazolamide MTT (AUC 0.909) and the absolute value of resting MTT (AUC 0.896). Pretreatment CTP with acetazolamide challenge could identify patients at risk for HPS after CAS. Although the CTP parameter that most accurately identified patients at risk for HPS was the absolute value of post-acetazolamide MTT, resting MTT was sufficiently accurate. (orig.)

  12. Link Prediction by De-anonymization: How We Won the Kaggle Social Network Challenge

    CERN Document Server

    Narayanan, Arvind; Rubinstein, Benjamin I P

    2011-01-01

    This paper describes the winning entry to the IJCNN 2011 Social Network Challenge run by Kaggle.com. The goal of the contest was to promote research on real-world link prediction, and the dataset was a graph obtained by crawling the popular Flickr social photo sharing website, with user identities scrubbed. By de-anonymizing much of the competition test set using our own Flickr crawl, we were able to effectively game the competition. Our attack represents a new application of de-anonymization to gaming machine learning contests, suggesting changes in how future competitions should be run. We introduce a new simulated annealing-based weighted graph matching algorithm for the seeding step of de-anonymization. We also show how to combine de-anonymization with link prediction---the latter is required to achieve good performance on the portion of the test set not de-anonymized---for example by training the predictor on the de-anonymized portion of the test set, and combining probabilistic predictions from de-anony...

  13. Prediction

    OpenAIRE

    Woollard, W.J.

    2006-01-01

    In this chapter we will look at the ways in which you can use ICT in the classroom to support hypothesis and prediction and how modern technology is enabling: pattern seeking, extrapolation and interpolation to meet the challenges of the information explosion of the 21st century.

  14. Challenges in the Tracking and Prediction of Scheduled-Vehicle Journeys

    DEFF Research Database (Denmark)

    Jensen, Christian Søndergaard; Tiesyte, Dalia

    2007-01-01

    vehicles deviate from their schedules. At the same time, there is a need for the infrastructure surrounding the vehicles to continually know the actual status of the vehicles. For example, anticipated arrival times of buses may have to be displayed at bus stops. It is a fundamental challenge to maintain......A number of applications in areas such as logistics, cargo delivery, and collective transport involve the management of fleets of vehicles that are expected to travel along known routes according to fixed schedules. Due to road construction, accidents, and other unanticipated conditions, the...... this type of knowledge with minimal cost. This paper characterizes the problem of real-time vehicle tracking using wireless communication, and of predicting the future status of the vehicles when their movements are restricted to given routes and when they follow schedules with a best effort. The paper...

  15. Response to challenging dose of x-rays as a predictive assay for molecular epidemiology

    International Nuclear Information System (INIS)

    Human biomonitoring, as a tool to identify or quantify the potential risk from genotoxic exposures, has gained increasing interest especially in the areas of cancer risk assessment and diseases treatment. Chromosome aberrations resulting from direct DNA breakage or from inhibition of DNA repair or synthesis, measured in peripheral blood lymphocytes have been used in occupational health surveillance programs in order to assess risks from exposures. Many results in our human monitoring studies have shown influence of the environmental or occupational exposure on the cytogenetic damage detected in lymphocytes, confirming both, the association with adverse health outcome and the influence of life style related confounding factors. Susceptibility to the environmental agent actions was also evaluated in lymphocytes in the studies of variation between responses to the challenging dose of UV or X-rays followed by the evaluation of the repair capacity of the DNA damage induced by a challenging dose. The induced and residual DNA damage was analyzed with the use of SCGE assay. Susceptibility and repair capacities of healthy donors and cancer patients were compared. Studies have shown a good correlation between DNA damage induced in vivo or in vitro and cytogenetic measures. Results from studies on susceptibilities and repair competence performed in occupationally exposed and unexposed 475 healthy donors and patients with diagnosed cancer are discussed. Significantly lower efficiency of repair process was observed in cancer patients. The possible effects on repair competency of various occupational exposures and influence of the diet and other confounding factors is shown. Although in our preliminary studies comet assay failed to detect DNA damage repair disorders in a teratoma immature infant, though, prospective use of a challenging dose of radiation combined with the comet assay as a predictive assay is suggested and limitation discussed

  16. Towards a predictive systems-level model of the human microbiome: progress, challenges, and opportunities.

    Science.gov (United States)

    Greenblum, Sharon; Chiu, Hsuan-Chao; Levy, Roie; Carr, Rogan; Borenstein, Elhanan

    2013-08-01

    The human microbiome represents a vastly complex ecosystem that is tightly linked to our development, physiology, and health. Our increased capacity to generate multiple channels of omic data from this system, brought about by recent advances in high throughput molecular technologies, calls for the development of systems-level methods and models that take into account not only the composition of genes and species in a microbiome but also the interactions between these components. Such models should aim to study the microbiome as a community of species whose metabolisms are tightly intertwined with each other and with that of the host, and should be developed with a view towards an integrated, comprehensive, and predictive modeling framework. Here, we review recent work specifically in metabolic modeling of the human microbiome, highlighting both novel methodologies and pressing challenges. We discuss various modeling approaches that lay the foundation for a full-scale predictive model, focusing on models of interactions between microbial species, metagenome-scale models of community-level metabolism, and models of the interaction between the microbiome and the host. Continued development of such models and of their integration into a multi-scale model of the microbiome will lead to a deeper mechanistic understanding of how variation in the microbiome impacts the host, and will promote the discovery of clinically relevant and ecologically relevant insights from the rich trove of data now available. PMID:23623295

  17. Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

    Science.gov (United States)

    Mangoni, Arduino A

    2012-05-01

    Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings. PMID:22512705

  18. Network discovery, characterization, and prediction : a grand challenge LDRD final report.

    Energy Technology Data Exchange (ETDEWEB)

    Kegelmeyer, W. Philip, Jr.

    2010-11-01

    This report is the final summation of Sandia's Grand Challenge LDRD project No.119351, 'Network Discovery, Characterization and Prediction' (the 'NGC') which ran from FY08 to FY10. The aim of the NGC, in a nutshell, was to research, develop, and evaluate relevant analysis capabilities that address adversarial networks. Unlike some Grand Challenge efforts, that ambition created cultural subgoals, as well as technical and programmatic ones, as the insistence on 'relevancy' required that the Sandia informatics research communities and the analyst user communities come to appreciate each others needs and capabilities in a very deep and concrete way. The NGC generated a number of technical, programmatic, and cultural advances, detailed in this report. There were new algorithmic insights and research that resulted in fifty-three refereed publications and presentations; this report concludes with an abstract-annotated bibliography pointing to them all. The NGC generated three substantial prototypes that not only achieved their intended goals of testing our algorithmic integration, but which also served as vehicles for customer education and program development. The NGC, as intended, has catalyzed future work in this domain; by the end it had already brought in, in new funding, as much funding as had been invested in it. Finally, the NGC knit together previously disparate research staff and user expertise in a fashion that not only addressed our immediate research goals, but which promises to have created an enduring cultural legacy of mutual understanding, in service of Sandia's national security responsibilities in cybersecurity and counter proliferation.

  19. Challenges in Downscaling Surge and Flooding Predictions Associated with Major Coastal Storm Events

    Science.gov (United States)

    Bowman, M. J.

    2015-12-01

    Coastal zone managers, elected officials and emergency planning personnel are continually seeking more reliable estimates of storm surge and inundation for better land use planning, the design, construction and operation of coastal defense systems, resilience evaluation and evacuation planning. Customers of modern regional weather and storm surge prediction models demand high resolution, speed, accuracy, with informative, interactive graphics and easy evaluation of potentially dangerous threats to life and property. These challenges continue to get more difficult as the demand for street-scale and even building-scale predictions increase. Fluctuations in sub-grid-scale wind and water velocities can lead to unsuspected, unanticipated and dangerous flooding in local communities. But how reliable and believable are these models given the inherent natural uncertainty and chaotic behavior in the underlying dynamics, which can lead to rapid and unexpected perturbations in the wind and pressure fields and hence coastal flooding? Traditionally this uncertainty has been quantified by the use of the ensemble method, where a suite of model runs are made with varying physics and initial conditions, presenting the mean and variance of the ensemble as the best metrics possible. But this assumes that each component is equally possible and is statistically independent of the others. But this is rarely true, although the "safety in numbers" approach is comforting to those faced with life and death decisions. An example of the ensemble method is presented for the trajectory of superstorm Sandy's storm center as it approached coastal New Jersey. If one were to ask the question "was Sandy a worst case scenario", the answer would be "no: small variations in the timing (vis-à-vis tide phase) and location of landfall could easily have led to an additional surge of +50 cm at The Battery NY with even more catastrophic consequences to those experienced".

  20. Gene Expression Prediction by Soft Integration and the Elastic Net—Best Performance of the DREAM3 Gene Expression Challenge

    OpenAIRE

    Mika Gustafsson; Michael Hörnquist

    2010-01-01

    Background: To predict gene expressions is an important endeavour within computational systems biology. It can both be a way to explore how drugs affect the system, as well as providing a framework for finding which genes are interrelated in a certain process. A practical problem, however, is how to assess and discriminate among the various algorithms which have been developed for this purpose. Therefore, the DREAM project invited the year 2008 to a challenge for predicting gene expression va...

  1. The Markyt visualisation, prediction and benchmark platform for chemical and gene entity recognition at BioCreative/CHEMDNER challenge.

    Science.gov (United States)

    Pérez-Pérez, Martin; Pérez-Rodríguez, Gael; Rabal, Obdulia; Vazquez, Miguel; Oyarzabal, Julen; Fdez-Riverola, Florentino; Valencia, Alfonso; Krallinger, Martin; Lourenço, Anália

    2016-01-01

    Biomedical text mining methods and technologies have improved significantly in the last decade. Considerable efforts have been invested in understanding the main challenges of biomedical literature retrieval and extraction and proposing solutions to problems of practical interest. Most notably, community-oriented initiatives such as the BioCreative challenge have enabled controlled environments for the comparison of automatic systems while pursuing practical biomedical tasks. Under this scenario, the present work describes the Markyt Web-based document curation platform, which has been implemented to support the visualisation, prediction and benchmark of chemical and gene mention annotations at BioCreative/CHEMDNER challenge. Creating this platform is an important step for the systematic and public evaluation of automatic prediction systems and the reusability of the knowledge compiled for the challenge. Markyt was not only critical to support the manual annotation and annotation revision process but also facilitated the comparative visualisation of automated results against the manually generated Gold Standard annotations and comparative assessment of generated results. We expect that future biomedical text mining challenges and the text mining community may benefit from the Markyt platform to better explore and interpret annotations and improve automatic system predictions.Database URL: http://www.markyt.org, https://github.com/sing-group/Markyt. PMID:27542845

  2. Low cost prediction of relative stabilities of hydrogen bonded complexes from atomic multipole moments for overly short intermolecular distances.

    Science.gov (United States)

    Beker, Wiktor; Langner, Karol M; Dyguda-Kazimierowicz, Edyta; Feliks, Mikołaj; Sokalski, W Andrzej

    2013-08-01

    The relative stability of biologically relevant, hydrogen bonded complexes with shortened distances can be assessed at low cost by the electrostatic multipole term alone more successfully than by ab initio methods. These results imply that atomic multipole moments may help improve ligand-receptor ranking predictions, particularly in cases where accurate structural data are not available. PMID:23696072

  3. 78 FR 70303 - Announcement of Requirements and Registration for the Predict the Influenza Season Challenge

    Science.gov (United States)

    2013-11-25

    ..., targeting resources and therefore reducing costs associated with influenza prevention and control, and... contest. Information is not collected for commercial marketing. Registering through the Challenge.gov...

  4. Blind prediction of host-guest binding affinities: A new SAMPL3 challenge

    OpenAIRE

    Muddana, Hari S.; Varnado, C. Daniel; Bielawski, Christopher W.; Urbach, Adam R.; Isaacs, Lyle; Geballe, Matthew T; Gilson, Michael K.

    2012-01-01

    The computational prediction of protein-ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands—i.e. host-guest systems – represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challe...

  5. Attracted to power: challenge/threat and promotion/prevention focus differentially predict the attractiveness of group power.

    Science.gov (United States)

    Scholl, Annika; Sassenrath, Claudia; Sassenberg, Kai

    2015-01-01

    Depending on their motivation, individuals prefer different group contexts for social interactions. The present research sought to provide more insight into this relationship. More specifically, we tested how challenge/threat and a promotion/prevention focus predict attraction to groups with high- or low-power. As such, we examined differential outcomes of threat and prevention focus as well as challenge and promotion focus that have often been regarded as closely related. According to regulatory focus, individuals should prefer groups that they expect to "feel right" for them to join: Low-power groups should be more attractive in a prevention (than a promotion) focus, as these groups suggest security-oriented strategies, which fit a prevention focus. High-power groups should be more attractive in a promotion (rather than a prevention) focus, as these groups are associated with promotion strategies fitting a promotion focus (Sassenberg et al., 2007). In contrast, under threat (vs. challenge), groups that allow individuals to restore their (perceived) lack of control should be preferred: Low-power groups should be less attractive under threat (than challenge) because they provide low resources which threatened individuals already perceive as insufficient and high-power groups might be more attractive under threat (than under challenge), because their high resources allow individuals to restore control. Two experiments (N = 140) supported these predictions. The attractiveness of a group often depends on the motivation to engage in what fits (i.e., prefer a group that feels right in the light of one's regulatory focus). However, under threat the striving to restore control (i.e., prefer a group allowing them to change the status quo under threat vs. challenge) overrides the fit effect, which may in turn guide individuals' behavior in social interactions. PMID:25904887

  6. State of the art and challenges in sequence based T-cell epitope prediction

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Hoof, Ilka; Lund, Ole;

    2010-01-01

    field has evolved significantly. Methods have now been developed that produce highly accurate binding predictions for many alleles and integrate both proteasomal cleavage and transport events. Moreover have so-called pan-specific methods been developed, which allow for prediction of peptide binding to......Sequence based T-cell epitope predictions have improved immensely in the last decade. From predictions of peptide binding to major histocompatibility complex molecules with moderate accuracy, limited allele coverage, and no good estimates of the other events in the antigen-processing pathway, the...... MHC alleles characterized by limited or no peptide binding data. Most of the developed methods are publicly available, and have proven to be very useful as a shortcut in epitope discovery. Here, we will go through some of the history of sequence-based predictions of helper as well as cytotoxic T cell...

  7. Assertiveness predicts threat and challenge reactions to potential stress among women.

    Science.gov (United States)

    Tomaka, J; Palacios, R; Schneider, K T; Colotla, M; Concha, J B; Herrald, M M

    1999-06-01

    In this study assertiveness as a moderator of stress reactions among women was examined. Specifically, the experimenters examined how high and low assertive women cognitively appraised, affectively and physiologically responded to, and behaviorally coped with the stress of giving an impromptu speech. High assertive women appraised the speech stressor as challenging, whereas low assertive women appraised the stressor as threatening. High assertive women also had a challenge pattern of autonomic response during the task, compared with the threat response of low assertive women. Afterward, the high assertive women reported experiencing less stress and negative emotion and greater positive emotion than did the low assertive women. Overall, the high assertive women's stress-related reactions indicated challenge, whereas the low assertive women's reactions indicated threat (see J. Tomaka, J. Blascovich, R. M. Kelsey, & C. L. Leitten, 1993). PMID:10402683

  8. Predicted and observed growth of Listeria monocytogenes in seafood challenge tests and in naturally contaminated cold smoked salmon

    DEFF Research Database (Denmark)

    Dalgaard, Paw; Jørgensen, Lasse Vigel

    1998-01-01

    The performance of the Pathogen Modelling Program, the Food MicroModel, the Murphy-model and the Ross-model for growth of L. monocytogenes was evaluated by comparison with data from 100 seafood challenge tests and data from 13 storage trials with naturally contaminated sliced vacuum-packed cold......-smoked salmon. Challenge tests with both cured and noncured products were studied, and graphs as well as the bias-and the accuracy factors were used for comparison of the observed and predicted growth. The Pathogen Modelling Program could not be successfully validated in seafood challenge tests. Growth rates...... were markedly overestimated and the mu(max)-bias factor was as high as 3.9 in challenge tests with cured products. On the basis of the effect of temperature, NaCl/a(w) and pH, the mu(max)-bias factor of the other three models studied, varied between 1.0 and 2.3 in the challenge tests with cured and...

  9. Development of patient specific cardiovascular models predicting dynamics in response to orthostatic stress challenges

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.

    2013-01-01

    Physiological realistic models of the controlled cardiovascular system are constructed and validated against clinical data. Special attention is paid to the control of blood pressure, cerebral blood flow velocity, and heart rate during postural challenges, including sit-to-stand and head-up tilt....

  10. Predictive models for the assessment of occupational exposure to chemicals: A new challenge for employers

    Directory of Open Access Journals (Sweden)

    Jan Piotr Gromiec

    2013-10-01

    Full Text Available Employers are obliged to carry out and document the risk associated with the use of chemical substances. The best but the most expensive method is to measure workplace concentrations of chemicals. At present no "measureless" method for risk assessment is available in Poland, but predictive models for such assessments have been developed in some countries. The purpose of this work is to review and evaluate the applicability of selected predictive methods for assessing occupational inhalation exposure and related risk to check the compliance with Occupational Exposure Limits (OELs, as well as the compliance with REACH obligations. Based on the literature data HSE COSHH Essentials, EASE, ECETOC TRA, Stoffenmanager, and EMKG-Expo-Tool were evaluated. The data on validation of predictive models were also examined. It seems that predictive models may be used as a useful method for Tier 1 assessment of occupational exposure by inhalation. Since the levels of exposure are frequently overestimated, they should be considered as "rational worst cases" for selection of proper control measures. Bearing in mind that the number of available exposure scenarios and PROC categories is limited, further validation by field surveys is highly recommended. Predictive models may serve as a good tool for preliminary risk assessment and selection of the most appropriate risk control measures in Polish small and medium size enterprises (SMEs providing that they are available in the Polish language. This also requires an extensive training of their future users. Med Pr 2013;64(5:699–716

  11. Predictive Control Strategies Used to Solve Challenges Related to Modern Railway Vehicles

    OpenAIRE

    Ngigi, R. W.; Pislaru, Crinela; Ball, Andrew; Fengshou, Gu; Anyakwo, Arthur

    2011-01-01

    This paper is an attempt to collate and critically appraise the recent advances in control strategies used to solve challenges related to railway vehicles which present nonlinearities and uncertainties. These strategies concentrate on stability of solid axle-wheelsets, guidance for wheelsets to provide the function of track following and curving to reduce all unnecessary creep forces and associated wear/noise. The focus is on active primary and secondary suspensions, braking and trac...

  12. The unexpected structure of the designed protein Octarellin V.1 forms a challenge for protein structure prediction tools.

    Science.gov (United States)

    Figueroa, Maximiliano; Sleutel, Mike; Vandevenne, Marylene; Parvizi, Gregory; Attout, Sophie; Jacquin, Olivier; Vandenameele, Julie; Fischer, Axel W; Damblon, Christian; Goormaghtigh, Erik; Valerio-Lepiniec, Marie; Urvoas, Agathe; Durand, Dominique; Pardon, Els; Steyaert, Jan; Minard, Philippe; Maes, Dominique; Meiler, Jens; Matagne, André; Martial, Joseph A; Van de Weerdt, Cécile

    2016-07-01

    Despite impressive successes in protein design, designing a well-folded protein of more 100 amino acids de novo remains a formidable challenge. Exploiting the promising biophysical features of the artificial protein Octarellin V, we improved this protein by directed evolution, thus creating a more stable and soluble protein: Octarellin V.1. Next, we obtained crystals of Octarellin V.1 in complex with crystallization chaperons and determined the tertiary structure. The experimental structure of Octarellin V.1 differs from its in silico design: the (αβα) sandwich architecture bears some resemblance to a Rossman-like fold instead of the intended TIM-barrel fold. This surprising result gave us a unique and attractive opportunity to test the state of the art in protein structure prediction, using this artificial protein free of any natural selection. We tested 13 automated webservers for protein structure prediction and found none of them to predict the actual structure. More than 50% of them predicted a TIM-barrel fold, i.e. the structure we set out to design more than 10years ago. In addition, local software runs that are human operated can sample a structure similar to the experimental one but fail in selecting it, suggesting that the scoring and ranking functions should be improved. We propose that artificial proteins could be used as tools to test the accuracy of protein structure prediction algorithms, because their lack of evolutionary pressure and unique sequences features. PMID:27181418

  13. Predicting volume responsiveness in spontaneously breathing patients: still a challenging problem

    OpenAIRE

    Magder, S

    2006-01-01

    The prediction of which patients respond to fluid infusion and which patients do not is an important issue in the intensive care setting. Assessment of this response by monitoring changes in some hemodynamic characteristics in relation to spontaneous breathing efforts would be very helpful for the management of the critically ill. This unfortunately remains a difficult clinical problem, as discussed in the previous issue of the journal. Technical factors and physiological factors limit the us...

  14. Panic Reactivity to Voluntary Hyperventilation Challenge Predicts Distress Tolerance to Bodily Sensations among Daily Cigarette Smokers

    OpenAIRE

    Marshall, Erin C.; Zvolensky, Michael J.; Vujanovic, Anka A.; Gregor, Kristin; Gibson, Laura E.; Leyro, Teresa M.

    2008-01-01

    The present investigation examined the extent to which panic reactivity to bodily sensations is related to distress tolerance (DT) among daily smokers. It was hypothesized that panic reactivity to an initial voluntary hyperventilation (i.e., whether participants met criteria for a DSM-IV panic attack; PA) would predict the relative degree of task persistence on a second hyperventilation trial (DT) above and beyond the variance accounted for by anxiety sensitivity (AS), negative affectivity (N...

  15. Predicting heart failure decompensation using cardiac implantable electronic devices: a review of practices and challenges.

    Science.gov (United States)

    Hawkins, Nathaniel M; Virani, Sean A; Sperrin, Matthew; Buchan, Iain E; McMurray, John J V; Krahn, Andrew D

    2016-08-01

    Cardiac implantable electronic devices include remote monitoring tools intended to guide heart failure management. The monitoring focus has been on averting hospitalizations by predicting worsening heart failure. However, although device measurements including intrathoracic impedance correlate with risk of decompensation, they individually predict hospitalizations with limited accuracy. Current 'crisis detection' methods involve repeatedly screening for impending decompensation, and do not adhere to the principles of diagnostic testing. Complex substrate, limited test performance, low outcome incidence, and long test to outcome times inevitably generate low positive and high negative predictive values. When combined with spectrum bias, the generalizability, incremental value, and cost-effectiveness of device algorithms are questionable. To avoid these pitfalls, remote monitoring may need to shift from crisis detection to health maintenance, keeping the patient within an ideal physiological range through continuous 'closed loop' interaction and dynamic therapy adjustment. Test performance must also improve, possibly through combination with physiological sensors in different dimensions, static baseline characteristics, and biomarkers. Complex modelling may tailor monitoring to individual phenotypes, and thus realize a personalized medicine approach. Future randomized controlled trials should carefully consider these issues, and ensure that the interventions tested are generalizable to clinical practice. PMID:26663507

  16. Last 20 years of gas hydrates in the oil industry : challenges and achievements in predicting pipeline blockage

    Energy Technology Data Exchange (ETDEWEB)

    Estanga, D.A.; Creek, J.; Subramanian, S.; Kini, R.A. [Chevron Energy Technology Co., Houston, TX (United States)

    2008-07-01

    This paper reviewed how the successes of the past 20 years have shaped the new hydrate focus. It also outlined innovative tools for hydrate plugging prediction. Tools such as CSMHyK-OLGA were developed to address the design and operational challenges associated with offshore production regarding flow assurance in the area of gas hydrates. The effort to understand the complex behavior of gas hydrates in multiphase flow has resulted in new hydrate blockage models. Although the hydrate community continues to debate the impact of kinetics, agglomeration, and oil chemistry effects on hydrate blockage formation in pipelines and wellbores, the petroleum industry still relies on thermodynamic strategies that completely prevent hydrates in production systems. However, these complex strategies such as thermal insulation, electric heating, dead oil displacement, and methanol injection are costly, particularly for marginal fields. As such, research continues in developing a comprehensive multiphase flow simulator capable of handling the transient aspects of production operations, notably shut-in, restart, blowdown and blockage prediction. Model predictions are leading to new operating strategies based on risk management approach. This paper discussed the challenges and opportunities that have shifted the focus from prevention of hydrates to prevention of blockage. Some initial successes in the development of a first generation empirical tool for the prediction of hydrate blockages in flow lines were also presented along with new experimental data that explained how hydrate blockages can manifest in the field. It was concluded that additional research is needed to solve the problem of hydrate plugging mechanism. 12 refs., 6 figs.

  17. Challenges in Dynamic Pressure and Stress Predictions at No-Load Operation in Hydraulic Turbines

    Science.gov (United States)

    Nennemann, B.; Morissette, J. F.; Chamberland-Lauzon, J.; Monette, C.; Braun, O.; Melot, M.; Coutu, A.; Nicolle, J.; Giroux, A. M.

    2014-03-01

    Some of the potentially most damaging continuous operating conditions for hydraulic turbines are the no-load (NL) conditions. At NL conditions the flow passes through the turbine without power generation, but with non-negligible flow rate, and therefore all the potential energy in the flow has to be dissipated. This takes place through a mechanism where the runner channels are partially pumping, thus generating large scale unsteady vortex structures which, by their nature, break down into smaller and smaller vortices until energy dissipation occurs at the smallest scales. This type of flow, dominated by its turbulent character, is inherently difficult to simulate by means of numerical methods since turbulence model and numerical dissipation have a major influence. The resulting dynamic loads on the runner are largely of stochastic nature, exciting a broad band of frequencies and thus, almost always interact with at least one deformation mode. The presented investigations are aimed at predicting the effect of the unsteady NL pressure loads on the fatigue life of a Francis turbine runner. A combination of computational fluid dynamics (CFD) and finite element analysis (FEA) methods has been employed. The results from transient CFD simulations are presented. Comparison of the results with prototype strain gauge measurements at no load conditions shows that the stochastic nature and the approximate range of the dynamic stresses can be predicted.

  18. Challenges in Dynamic Pressure and Stress Predictions at No-Load Operation in Hydraulic Turbines

    International Nuclear Information System (INIS)

    Some of the potentially most damaging continuous operating conditions for hydraulic turbines are the no-load (NL) conditions. At NL conditions the flow passes through the turbine without power generation, but with non-negligible flow rate, and therefore all the potential energy in the flow has to be dissipated. This takes place through a mechanism where the runner channels are partially pumping, thus generating large scale unsteady vortex structures which, by their nature, break down into smaller and smaller vortices until energy dissipation occurs at the smallest scales. This type of flow, dominated by its turbulent character, is inherently difficult to simulate by means of numerical methods since turbulence model and numerical dissipation have a major influence. The resulting dynamic loads on the runner are largely of stochastic nature, exciting a broad band of frequencies and thus, almost always interact with at least one deformation mode. The presented investigations are aimed at predicting the effect of the unsteady NL pressure loads on the fatigue life of a Francis turbine runner. A combination of computational fluid dynamics (CFD) and finite element analysis (FEA) methods has been employed. The results from transient CFD simulations are presented. Comparison of the results with prototype strain gauge measurements at no load conditions shows that the stochastic nature and the approximate range of the dynamic stresses can be predicted

  19. The admixed population structure in Danish Jersey dairy cattle challenges accurate genomic predictions

    DEFF Research Database (Denmark)

    Thomasen, Jørn Rind; Sørensen, Anders Christian; Su, Guosheng; Madsen, Per; Lund, Mogens Sandø; Guldbrandtsen, Bernt

    2013-01-01

    The main purpose of this study is to evaluate whether the population structure in Danish Jersey known from the history of the breed also is reflected in the markers. This is done by comparing the linkage disequilibrium and persistence of phase for subgroups of Jersey animals with high proportions...... structure incorporated 1,730 genotyped Jersey animals. In total 39,542 SNP markers were included in the analysis. The 1,079 genotyped bulls with de-regressed proof for udder health were used in the analysis for the predictions of the genomic breeding values. A range of random regressions models that...... included the breed origin were analyzed and compared to a basic genomic model that assumes a homogeneous breed structure. The main finding in this study is that the importation of germ plasma from the US Jersey population is readily reflected in the genomes of modern Danish Jersey animals. Firstly, linkage...

  20. Current Challenges in Glioblastoma: Intratumour Heterogeneity, Residual Disease, and Models to Predict Disease Recurrence.

    Science.gov (United States)

    Ellis, Hayley P; Greenslade, Mark; Powell, Ben; Spiteri, Inmaculada; Sottoriva, Andrea; Kurian, Kathreena M

    2015-01-01

    Glioblastoma (GB) is the most common primary malignant brain tumor, and despite the availability of chemotherapy and radiotherapy to combat the disease, overall survival remains low with a high incidence of tumor recurrence. Technological advances are continually improving our understanding of the disease, and in particular, our knowledge of clonal evolution, intratumor heterogeneity, and possible reservoirs of residual disease. These may inform how we approach clinical treatment and recurrence in GB. Mathematical modeling (including neural networks) and strategies such as multiple sampling during tumor resection and genetic analysis of circulating cancer cells, may be of great future benefit to help predict the nature of residual disease and resistance to standard and molecular therapies in GB. PMID:26636033

  1. Challenges in reactive transport modeling for prediction of geometry evolution in fractured carbonate rocks

    Science.gov (United States)

    Peters, C. A.; Deng, H.; Guo, B.; Fitts, J. P.

    2014-12-01

    Carbonate minerals are common in sedimentary rocks including in formations that serve as caprock seals. These formations are intended to stop migration of injected fluids, such as CO2 in the context of geologic carbon sequestration, ensuring permanent isolation from the atmosphere. Fractures in caprocks may allow injected CO2 and pressurized brine to escape. If the caprock contains substantial amounts of carbonates, flow of acidified fluids may cause substantial mineral dissolution which would increase the leakiness over time. Our research seeks to understand this process with particular attention to the evolution of fracture geometry and the implications for flow permeability. Our work combines high-pressure core flow experiments, x-ray imaging methods, reactive transport modeling, and computational fluid dynamics simulations. We have found that fracture permeability can increase substantially as a result of calcite dissolution. However, the extent of permeability increase is affected by complex alterations in fracture geometry. Newly-formed surface roughness and microporosity diminishes flow relative to what would be predicted by conventional practical models such as the local cubic law model. In contrast, channelization could lead to higher-than-expected flow rates because such fractures would stabilize open flow paths against geomechanical closure forces. Modeling these processes requires fine-scale 2D, if not 3D, reactive transport flow models that simulate not only the increase in fracture aperture but also the evolution in fracture geometry. Development of computationally-tractable reactive transport models that accurately predict reaction-induced changes in fracture permeability is an ongoing research priority in our lab.

  2. Prediction of Canopy Heights over a Large Region Using Heterogeneous Lidar Datasets: Efficacy and Challenges

    Directory of Open Access Journals (Sweden)

    Ranjith Gopalakrishnan

    2015-08-01

    Full Text Available Generating accurate and unbiased wall-to-wall canopy height maps from airborne lidar data for large regions is useful to forest scientists and natural resource managers. However, mapping large areas often involves using lidar data from different projects, with varying acquisition parameters. In this work, we address the important question of whether one can accurately model canopy heights over large areas of the Southeastern US using a very heterogeneous dataset of small-footprint, discrete-return airborne lidar data (with 76 separate lidar projects. A unique aspect of this effort is the use of nationally uniform and extensive field data (~1800 forested plots from the Forest Inventory and Analysis (FIA program of the US Forest Service. Preliminary results are quite promising: Over all lidar projects, we observe a good correlation between the 85th percentile of lidar heights and field-measured height (r = 0.85. We construct a linear regression model to predict subplot-level dominant tree heights from distributional lidar metrics (R2 = 0.74, RMSE = 3.0 m, n = 1755. We also identify and quantify the importance of several factors (like heterogeneity of vegetation, point density, the predominance of hardwoods or softwoods, the average height of the forest stand, slope of the plot, and average scan angle of lidar acquisition that influence the efficacy of predicting canopy heights from lidar data. For example, a subset of plots (coefficient of variation of vegetation heights <0.2 significantly reduces the RMSE of our model from 3.0–2.4 m (~20% reduction. We conclude that when all these elements are factored into consideration, combining data from disparate lidar projects does not preclude robust estimation of canopy heights.

  3. Gene expression prediction by soft integration and the elastic net-best performance of the DREAM3 gene expression challenge.

    Directory of Open Access Journals (Sweden)

    Mika Gustafsson

    Full Text Available BACKGROUND: To predict gene expressions is an important endeavour within computational systems biology. It can both be a way to explore how drugs affect the system, as well as providing a framework for finding which genes are interrelated in a certain process. A practical problem, however, is how to assess and discriminate among the various algorithms which have been developed for this purpose. Therefore, the DREAM project invited the year 2008 to a challenge for predicting gene expression values, and here we present the algorithm with best performance. METHODOLOGY/PRINCIPAL FINDINGS: We develop an algorithm by exploring various regression schemes with different model selection procedures. It turns out that the most effective scheme is based on least squares, with a penalty term of a recently developed form called the "elastic net". Key components in the algorithm are the integration of expression data from other experimental conditions than those presented for the challenge and the utilization of transcription factor binding data for guiding the inference process towards known interactions. Of importance is also a cross-validation procedure where each form of external data is used only to the extent it increases the expected performance. CONCLUSIONS/SIGNIFICANCE: Our algorithm proves both the possibility to extract information from large-scale expression data concerning prediction of gene levels, as well as the benefits of integrating different data sources for improving the inference. We believe the former is an important message to those still hesitating on the possibilities for computational approaches, while the latter is part of an important way forward for the future development of the field of computational systems biology.

  4. LNG fires: A review of experimental results, models and hazard prediction challenges

    International Nuclear Information System (INIS)

    A number of experimental investigations of LNG fires (of sizes 35 m diameter and smaller) were undertaken, world wide, during the 1970s and 1980s to study their physical and radiative characteristics. This paper reviews the published data from several of these tests including from the largest test to date, the 35 m, Montoir tests. Also reviewed in this paper is the state of the art in modeling LNG pool and vapor fires, including thermal radiation hazard modeling. The review is limited to considering the integral and semi-empirical models (solid flame and point source); CFD models are not reviewed. Several aspects of modeling LNG fires are reviewed including, the physical characteristics, such as the (visible) fire size and shape, tilt and drag in windy conditions, smoke production, radiant thermal output, etc., and the consideration of experimental data in the models. Comparisons of model results with experimental data are indicated and current deficiencies in modeling are discussed. The requirements in the US and European regulations related to LNG fire hazard assessment are reviewed, in brief, in the light of model inaccuracies, criteria for hazards to people and structures, and the effects of mitigating circumstances. The paper identifies: (i) critical parameters for which there exist no data, (ii) uncertainties and unknowns in modeling and (iii) deficiencies and gaps in current regulatory recipes for predicting hazards

  5. Predicting malaria vector distribution under climate change scenarios in China: Challenges for malaria elimination

    Science.gov (United States)

    Ren, Zhoupeng; Wang, Duoquan; Ma, Aimin; Hwang, Jimee; Bennett, Adam; Sturrock, Hugh J. W.; Fan, Junfu; Zhang, Wenjie; Yang, Dian; Feng, Xinyu; Xia, Zhigui; Zhou, Xiao-Nong; Wang, Jinfeng

    2016-02-01

    Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control activities for sustaining elimination and preventing reintroduction of malaria. In China, however, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of climate change on four dominant malaria vectors (An. dirus, An. minimus, An. lesteri and An. sinensis) using species distribution models for two future decades: the 2030 s and the 2050 s. Simulation-based estimates suggest that the environmentally suitable area (ESA) for An. dirus and An. minimus would increase by an average of 49% and 16%, respectively, under all three scenarios for the 2030 s, but decrease by 11% and 16%, respectively in the 2050 s. By contrast, an increase of 36% and 11%, respectively, in ESA of An. lesteri and An. sinensis, was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios. in the 2050 s. In total, we predict a substantial net increase in the population exposed to the four dominant malaria vectors in the decades of the 2030 s and 2050 s, considering land use changes and urbanization simultaneously. Strategies to achieve and sustain malaria elimination in China will need to account for these potential changes in vector distributions and receptivity.

  6. Concepts and challenges in cancer risk prediction for the space radiation environment.

    Science.gov (United States)

    Barcellos-Hoff, Mary Helen; Blakely, Eleanor A; Burma, Sandeep; Fornace, Albert J; Gerson, Stanton; Hlatky, Lynn; Kirsch, David G; Luderer, Ulrike; Shay, Jerry; Wang, Ya; Weil, Michael M

    2015-07-01

    Cancer is an important long-term risk for astronauts exposed to protons and high-energy charged particles during travel and residence on asteroids, the moon, and other planets. NASA's Biomedical Critical Path Roadmap defines the carcinogenic risks of radiation exposure as one of four type I risks. A type I risk represents a demonstrated, serious problem with no countermeasure concepts, and may be a potential "show-stopper" for long duration spaceflight. Estimating the carcinogenic risks for humans who will be exposed to heavy ions during deep space exploration has very large uncertainties at present. There are no human data that address risk from extended exposure to complex radiation fields. The overarching goal in this area to improve risk modeling is to provide biological insight and mechanistic analysis of radiation quality effects on carcinogenesis. Understanding mechanisms will provide routes to modeling and predicting risk and designing countermeasures. This white paper reviews broad issues related to experimental models and concepts in space radiation carcinogenesis as well as the current state of the field to place into context recent findings and concepts derived from the NASA Space Radiation Program. PMID:26256633

  7. Predicted and observed growth of Listeria monocytogenes in seafood challenge tests and in naturally contaminated cold smoked salmon

    DEFF Research Database (Denmark)

    Dalgaard, Paw; Jørgensen, Lasse Vigel

    The performance of the Pathogen Modelling Program, the Food MicroModel, the Murphy-model and the Ross-model for growth of L. monocytogenes was evaluated by comparison with data from 100 seafood challenge tests and data from 13 storage trials with naturally contaminated sliced vacuum-packed cold...... products. Temperature, pH, NaCl/a(w) and lactate were measured in the storage trials and on the basis of these parameters, the Food MicroModel mu(max)-bias factor was 5.2. Clearly, the model could not be successfully validated with naturally contaminated cold-smoked salmon. To improve the applicability of...... predictive models to fish products, it is suggested to include studies with naturally contaminated products in the development and validation of models with seafood pathogens. (C) 1998 Elsevier Science B.V...

  8. The Challenges of Developing a Framework for Global Water Cycle Monitoring and Prediction (Alfred Wegener Medal Lecture)

    Science.gov (United States)

    Wood, Eric F.

    2014-05-01

    The Global Earth Observation System of Systems (GEOSS) Water Strategy ("From Observations to Decisions") recognizes that "water is essential for ensuring food and energy security, for facilitating poverty reduction and health security, and for the maintenance of ecosystems and biodiversity", and that water cycle data and observations are critical for improved water management and water security - especially in less developed regions. The GEOSS Water Strategy has articulated a number of goals for improved water management, including flood and drought preparedness, that include: (i) facilitating the use of Earth Observations for water cycle observations; (ii) facilitating the acquisition, processing, and distribution of data products needed for effective management; (iii) providing expertise, information systems, and datasets to the global, regional, and national water communities. There are several challenges that must be met to advance our capability to provide near real-time water cycle monitoring, early warning of hydrological hazards (floods and droughts) and risk assessment under climate change, regionally and globally. Current approaches to monitoring and predicting hydrological hazards are limited in many parts of the world, and especially in developing countries where national capacity is limited and monitoring networks are inadequate. This presentation describes the developments at Princeton University towards a seamless monitoring and prediction framework at all time scales that allows for consistent assessment of water variability from historic to current conditions, and from seasonal and decadal predictions to climate change projections. At the center of the framework is an experimental, global water cycle monitoring and seasonal forecast system that has evolved out of regional and continental systems for the US and Africa. The system is based on land surface hydrological modeling that is driven by satellite remote sensing precipitation to predict

  9. Advances and Challenges In Uncertainty Quantification with Application to Climate Prediction, ICF design and Science Stockpile Stewardship

    Science.gov (United States)

    Klein, R.; Woodward, C. S.; Johannesson, G.; Domyancic, D.; Covey, C. C.; Lucas, D. D.

    2012-12-01

    Uncertainty Quantification (UQ) is a critical field within 21st century simulation science that resides at the very center of the web of emerging predictive capabilities. The science of UQ holds the promise of giving much greater meaning to the results of complex large-scale simulations, allowing for quantifying and bounding uncertainties. This powerful capability will yield new insights into scientific predictions (e.g. Climate) of great impact on both national and international arenas, allow informed decisions on the design of critical experiments (e.g. ICF capsule design, MFE, NE) in many scientific fields, and assign confidence bounds to scientifically predictable outcomes (e.g. nuclear weapons design). In this talk I will discuss a major new strategic initiative (SI) we have developed at Lawrence Livermore National Laboratory to advance the science of Uncertainty Quantification at LLNL focusing in particular on (a) the research and development of new algorithms and methodologies of UQ as applied to multi-physics multi-scale codes, (b) incorporation of these advancements into a global UQ Pipeline (i.e. a computational superstructure) that will simplify user access to sophisticated tools for UQ studies as well as act as a self-guided, self-adapting UQ engine for UQ studies on extreme computing platforms and (c) use laboratory applications as a test bed for new algorithms and methodologies. The initial SI focus has been on applications for the quantification of uncertainty associated with Climate prediction, but the validated UQ methodologies we have developed are now being fed back into Science Based Stockpile Stewardship (SSS) and ICF UQ efforts. To make advancements in several of these UQ grand challenges, I will focus in talk on the following three research areas in our Strategic Initiative: Error Estimation in multi-physics and multi-scale codes ; Tackling the "Curse of High Dimensionality"; and development of an advanced UQ Computational Pipeline to enable

  10. Electronic coarse graining enhances the predictive power of molecular simulation allowing challenges in water physics to be addressed

    CERN Document Server

    Cipcigan, Flaviu S; Crain, Jason; Martyna, Glenn J

    2016-01-01

    One key factor that limits the predictive power of molecular dynamics simulations is the accuracy and transferability of the input force field. Force fields are challenged by heterogeneous environments, where electronic responses give rise to biologically important forces such as many-body polarisation and dispersion. The importance of polarisation was recognised early-on and described by Cochran in 1959 [Philosophical Magazine 4 (1959) 1082-1086]. However, dispersion forces are still treated at the two-body level and in the dipole limit, although the importance of three-body terms in the condensed phase was demonstrated by Barker in the 1980s [Phys. Rev. Lett. 57 (1986) 230-233]. A way of treating both polarisation and dispersion on an equal basis is to coarse grain the electrons a molecular moiety to a single quantum harmonic oscillator, as suggested as early as the 1960s by Hirschfelder, Curtiss and Bird [The Molecular Theory of Gases and Liquids (1954)]. This treatment, when solved in the strong coupling ...

  11. Radio-ligand receptor binding assay in vitro and animal biodistribution in vivo of 99Tccm-N-ethyl-N2S2-memantine as a potential NMDA receptor imaging agent

    International Nuclear Information System (INIS)

    The pharmacologic characteristics of 99Tcm-N-ethyl-N2S2-memantine, an NMDA receptor imaging agent, was investigated. It was prepared by a one-step reaction from N-ethyl-N2S2-memantine. The affinity and specificity were determined by radio-ligand receptor binding assay(RRA). Biodistribution in vivo in mice was performed. The results showed that 99Tcm-N-ethyl-N2S2-memantine bound to a single site on NMDA receptor with a Kd of 584.32 nmol/L and a Bmax of 267.05 nmol/mg. A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor, such as ketamine and (+) -MK-801. The biodistribution exhibited rapid uptake and favorable retention in mice brains. The major radioactivity was metabolized by the hepatic system. A two-compartment model of C=4.49e-0.083t + 1.42e-0.0016twas established, and the half life was 8.35 min in blood. In conclusion, the new radio-ligand 99Tcm-N-ethyl-N2S2-Memantine has a moderate affinity and specific binding to NMDA receptor, and can easily cross the blood-brain barrier (BBB). Therefore, it may be a potential NMDA receptor imaging agent. (authors)

  12. Prediction

    CERN Document Server

    Sornette, Didier

    2010-01-01

    This chapter first presents a rather personal view of some different aspects of predictability, going in crescendo from simple linear systems to high-dimensional nonlinear systems with stochastic forcing, which exhibit emergent properties such as phase transitions and regime shifts. Then, a detailed correspondence between the phenomenology of earthquakes, financial crashes and epileptic seizures is offered. The presented statistical evidence provides the substance of a general phase diagram for understanding the many facets of the spatio-temporal organization of these systems. A key insight is to organize the evidence and mechanisms in terms of two summarizing measures: (i) amplitude of disorder or heterogeneity in the system and (ii) level of coupling or interaction strength among the system's components. On the basis of the recently identified remarkable correspondence between earthquakes and seizures, we present detailed information on a class of stochastic point processes that has been found to be particu...

  13. Predicting tumor sizes of ductal carcinoma in situ from immunohistochemical images using a novel approach of mathematical pathology: preliminary results, potentials and challenges ahead

    Science.gov (United States)

    Chuang, Yao-Li; Edgerton, Mary; Macklin, Paul; Yang, Wei; Bearer, Elaine; Cristini, Vittorio

    2012-02-01

    Differential equation models have recently drawn increasing attentions as a useful tool to help advance the knowledge in cancer research. However, challenges remain for applying such models to clinical practices on a patient-specific basis to assist surgical decisions. Clinical diagnoses essentially at a single time point are often insufficient to fully constrain the time-dependent differential equations. Here we present a novel mathematical pathology approach, identifying robust indicators for time-invariant predictions of the model that can be used for surgical planning. We demonstrate this approach by predicting the sizes of ductal carcinoma in situ by calibrating model parameters from immunohistochemical images. Our preliminary studies of 17 excised tumor cases resulted in a better agreement with the actual measured sizes than the other estimates available to us, showing the potential of our approach for patient-specific cancer diagnosis. Conversely, our studies also revealed challenges to overcome before we can take this approach to the next level.

  14. Bronchial histamine challenge in the diagnosis of asthma. The predictive value of changes in airway resistance determined by the interrupter method

    DEFF Research Database (Denmark)

    Madsen, F; Holstein-Rathlou, N H; Frølund, L;

    1986-01-01

    The predictive value of a bronchial challenge with histamine was determined in a prospective survey on a population with a high prevalence of asthma (0.62). Without knowledge of the bronchial responsiveness 133 patients were classified as asthmatics (83) or non-asthmatics (50) according to...... variation in peak expiratory flow rate and medical history. Response to challenge was determined by the interrupter method, and the concentration of histamine inducing a 40% increase in resistance to breathing (PC40-Rt) was calculated from the log dose response curve. When defining a positive test as a test....../ml the predictive value of a negative test in the diagnosis of asthma was increased to 0.81. The interrupter technique is suitable for diagnostic purposes in the detection and exclusion of bronchial asthma....

  15. Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

    Science.gov (United States)

    The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

  16. Challenging the state-of-the-art in protein structure prediction: Highlights of experimental target structures for the 10th Critical Assessment of Techniques for Protein Structure Prediction Experiment CASP10

    Science.gov (United States)

    Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J. Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V.; Craig, Timothy K.; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut; Ma, Xiaolei; Nelson, Daniel C.; van Raaij, Mark J.; Rohwer, Forest; Segall, Anca; Seguritan, Victor; Zeth, Kornelius; Schwede, Torsten

    2014-01-01

    For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, over 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this paper, authors of some of the most challenging targets discuss which specific scientific question motivated the experimental structure determination of the target protein, which structural features were especially interesting from a structural or functional perspective, and to what extent these features were correctly reproduced in the predictions submitted to CASP10. Specifically, the following targets will be presented: the acid-gated urea channel, a difficult to predict trans-membrane protein from the important human pathogen Helicobacter pylori; the structure of human interleukin IL-34, a recently discovered helical cytokine; the structure of a functionally uncharacterized enzyme OrfY from Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan domain of mimivirus sulfhydryl oxidase R596; the fibre protein gp17 from bacteriophage T7; the Bacteriophage CBA-120 tailspike protein; a virus coat protein from metagenomic samples of the marine environment; and finally an unprecedented class of structure prediction targets based on engineered disulfide-rich small proteins. PMID:24318984

  17. The Interaction of Nicotine Withdrawal and Panic Disorder in the Prediction of Panic-relevant Responding to a Biological Challenge

    OpenAIRE

    Leyro, Teresa M.; Zvolensky, Michael J.

    2012-01-01

    The current investigation evaluated nicotine withdrawal symptoms elicited by 12 hours of smoking deprivation on anxious and fearful responding to bodily sensations among daily smokers with and without Panic Disorder (PD). It was hypothesized that smokers with PD who were experiencing greater levels of nicotine withdrawal would experience the greatest levels of fearful responding to, and delayed recovery from, a 10% carbon dioxide-enriched air (CO2) biological challenge procedure. Participants...

  18. Evaluating Emotional Sensitivity and Tolerance Factors in the Prediction of Panic-Relevant Responding to a Biological Challenge

    OpenAIRE

    Kutz, Amanda; Marshall, Erin; Bernstein, Amit; Zvolensky, Michael J.

    2010-01-01

    The current study investigated anxiety sensitivity, distress tolerance (Simons & Gaher, 2005), and discomfort intolerance (Schmidt, Richey, Cromer, & Buckner, 2007) in relation to panic-relevant responding (i.e., panic attack symptoms and panic-relevant cognitions) to a 10% carbon-dioxide enriched air challenge. Participants were 216 adults (52.6% female; M age = 22.4, SD = 9.0). A series of hierarchical multiple regressions was conducted with covariates of negative affectivity and past-year ...

  19. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group

    DEFF Research Database (Denmark)

    Thunnissen, Erik; Kerr, Keith M; Herth, Felix J F;

    2012-01-01

    Until recently, the division of pulmonary carcinomas into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection. Due to the emergence of new treatment options subtyping of NSCLC and predictive testing have become mandatory. A practical approach to...... NSCLC subtype (squamous cell vs. adenocarcinoma), as in small diagnostic samples specific subtyping is frequently on morphological grounds alone not feasible (NSCLC-NOS), (iii) molecular testing. To allow the extended diagnostic and predictive examination (i) tissue sampling should be maximized whenever...

  20. End point prick test: could this new test be used to predict the outcome of oral food challenge in children with cow's milk allergy?

    OpenAIRE

    Bellini Federica; Ricci Giampaolo; Dondi Arianna; Piccinno Valentina; Angelini Federico; Pession Andrea

    2011-01-01

    Abstract Background Cow's milk allergy (CMA) is the most frequent food allergy in childhood; the trend of CMA is often characterized by a progressive improvement to achieve tolerance in the first 4 to 5 years of life. It has been observed that specific IgE (sIgE) towards cow's milk proteins decrease when the age increases. Although food allergy can be easily diagnosed, it is difficult to predict the outcome of the oral food challenge (OFC), that remains the gold standard in the diagnosis of f...

  1. Safety Evaluation of Sous Vide-Processed Products with Respect to Nonproteolytic Clostridium botulinum by Use of Challenge Studies and Predictive Microbiological Models

    OpenAIRE

    Hyytiä-Trees, Eija; Skyttä, Eija; Mokkila, Mirja; Kinnunen, Arvo; Lindström, Miia; Lähteenmäki, Liisa; Ahvenainen, Raija; Korkeala, Hannu

    2000-01-01

    Sixteen different types of sous vide-processed products were evaluated for safety with respect to nonproteolytic group II Clostridium botulinum by using challenge tests with low (2.0-log-CFU/kg) and high (5.3-log-CFU/kg) inocula and two currently available predictive microbiological models, Food MicroModel (FMM) and Pathogen Modeling Program (PMP). After thermal processing, the products were stored at 4 and 8°C and examined for the presence of botulinal spores and neurotoxin on the sell-by da...

  2. The prediction of PAHs bioavailability in soils using chemical methods: state of the art and future challenges.

    Science.gov (United States)

    Cachada, A; Pereira, R; da Silva, E Ferreira; Duarte, A C

    2014-02-15

    The evaluation of the available fraction of hydrophobic organic contaminants (HOCs) is extremely important for assessing their risk to the environment and human health. This available fraction, which can be solubilized and/or easily extracted, is believed to be the most accessible for bioaccumulation, biosorption and/or transformation by organisms. Based on this, two main types of chemical methods have been developed, closely related to the concepts of bioaccessibility and freely available concentrations: non-exhaustive extractions and biomimetic methods. Since bioavailability is species and compound specific, this work focused only in one of the most widespread group of HOCs in soils: polycyclic aromatic hydrocarbons (PAHs). This study aims at producing a state of the art knowledge base on bioavailability and chemical availability of PAHs in soils, clarifying which chemical methods can provide a better prediction of an organism exposure, and which are the most promising ones. Therefore, a review of the processes involved on PAHs availability to microorganisms, earthworms and plants was performed and the outputs given by the different chemical methods were evaluated. The suitability of chemical methods to predict bioavailability of the 16 US EPA PAHs in dissimilar naturally contaminated soils was not yet demonstrated, being especially difficult for high molecular weight compounds. Even though the potential to predict microbial mineralization using non-exhaustive extractions is promising, it will be very difficult to achieve for earthworms and plants, due to the complexity of accumulation mechanisms which are not taken into account by chemical methods. Yet, the existing models could be improved by determining compound, species and site specific parameters. Moreover, chemical availability can be very useful to understand the bioavailability processes and the behavior of PAHs in soils. The inclusion of chemical methods on risk assessment has been suggested and it is

  3. Use of systolic pressure variation to predict the cardiovascular response to mini-fluid challenge in anaesthetised dogs.

    Science.gov (United States)

    Rabozzi, R; Franci, P

    2014-11-01

    Systolic pressure variation (SPV), the maximum variation in systolic pressure values following a single positive pressure breath delivered by controlled mechanical ventilation (CMV), is highly correlated with volaemia in dogs. The aim of this study was to determine an SPV value that would indicate when fluid administration would be beneficial in clinical practice. Twenty-six client-owned dogs were anaesthetised, following which CMV with a peak inspiratory pressure (PIP) of 8 cmH2O was applied. After SPV measurement and recording of heart rate (HR) and blood pressure (BP), 3 mL/kg fluid were administered, then HR and BP were recorded again. Dogs exhibiting a 10% decrease in HR and/or an increase in BP were defined as responders, and their SPV pre-bolus was analysed retrospectively. SPV values > 4 mmHg or >4.5% predicted haemodynamic improvement in dogs with normal cardiovascular function, with a sensitivity of 90% and a specificity of 87%. The area under the curve receiver operating characteristic value for SPV was 0.931 mmHg (95% confidence interval, CI, 0.76-0.99 mmHg) and 0.944% (95% CI 0.78-0.99%). It is proposed that SPV values > 4.5% in dogs with a normal cardiovascular function, anaesthetised with isoflurane in oxygen and air, and on CMV (PIP 8 cmH2O), can be used to predict a cardiovascular response (>10% increase in mean arterial BP and/or >10% decrease in heart rate). PMID:25199508

  4. Safety Evaluation of Sous Vide-Processed Products with Respect to Nonproteolytic Clostridium botulinum by Use of Challenge Studies and Predictive Microbiological Models

    Science.gov (United States)

    Hyytiä-Trees, Eija; Skyttä, Eija; Mokkila, Mirja; Kinnunen, Arvo; Lindström, Miia; Lähteenmäki, Liisa; Ahvenainen, Raija; Korkeala, Hannu

    2000-01-01

    Sixteen different types of sous vide-processed products were evaluated for safety with respect to nonproteolytic group II Clostridium botulinum by using challenge tests with low (2.0-log-CFU/kg) and high (5.3-log-CFU/kg) inocula and two currently available predictive microbiological models, Food MicroModel (FMM) and Pathogen Modeling Program (PMP). After thermal processing, the products were stored at 4 and 8°C and examined for the presence of botulinal spores and neurotoxin on the sell-by date and 7 days after the sell-by date. Most of the thermal processes were found to be inadequate for eliminating spores, even in low-inoculum samples. Only 2 of the 16 products were found to be negative for botulinal spores and neurotoxin at both sampling times. Two products at the high inoculum level showed toxigenesis during storage at 8°C, one of them at the sell-by date. The predictions generated by both the FMM thermal death model and the FMM and PMP growth models were found to be inconsistent with the observed results in a majority of the challenges. The inaccurate predictions were caused by the limited number and range of the controlling factors in the models. Based on this study, it was concluded that the safety of sous vide products needs to be carefully evaluated product by product. Time-temperature combinations used in thermal treatments should be reevaluated to increase the efficiency of processing, and the use of additional antibotulinal hurdles, such as biopreservatives, should be assessed. PMID:10618228

  5. Skin prick testing with extensively heated milk or egg products helps predict the outcome of an oral food challenge: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Faraj Zein

    2012-07-01

    Full Text Available Abstract Background Cow’s milk and hen’s egg are the most frequently encountered food allergens in the pediatric population. Skin prick testing (SPT with commercial extracts followed by an oral food challenge (OFC are routinely performed in the diagnostic investigation of these children. Recent evidence suggests that milk-allergic and/or egg-allergic individuals can often tolerate extensively heated (EH forms of these foods. This study evaluated the predictive value of a negative SPT with EH milk or egg in determining whether a child would tolerate an OFC to the EH food product. Methods Charts from a single allergy clinic were reviewed for any patient with a negative SPT to EH milk or egg, prepared in the form of a muffin. Data collected included age, sex, symptoms of food allergy, co-morbidities and the success of the OFC to the muffin. Results Fifty-eight patients had negative SPTs to the EH milk or egg in a muffin and underwent OFC to the appropriate EH food in the outpatient clinic. Fifty-five of these patients tolerated the OFC. The negative predictive value for the SPT with the EH food product was 94.8%. Conclusions SPT with EH milk or egg products was predictive of a successful OFC to the same food. Larger prospective studies are required to substantiate these findings.

  6. International challenge to predict the impact of radioxenon releases from medical isotope production on a comprehensive nuclear test ban treaty sampling station.

    Science.gov (United States)

    Eslinger, Paul W; Bowyer, Ted W; Achim, Pascal; Chai, Tianfeng; Deconninck, Benoit; Freeman, Katie; Generoso, Sylvia; Hayes, Philip; Heidmann, Verena; Hoffman, Ian; Kijima, Yuichi; Krysta, Monika; Malo, Alain; Maurer, Christian; Ngan, Fantine; Robins, Peter; Ross, J Ole; Saunier, Olivier; Schlosser, Clemens; Schöppner, Michael; Schrom, Brian T; Seibert, Petra; Stein, Ariel F; Ungar, Kurt; Yi, Jing

    2016-06-01

    The International Monitoring System (IMS) is part of the verification regime for the Comprehensive Nuclear-Test-Ban-Treaty Organization (CTBTO). At entry-into-force, half of the 80 radionuclide stations will be able to measure concentrations of several radioactive xenon isotopes produced in nuclear explosions, and then the full network may be populated with xenon monitoring afterward. An understanding of natural and man-made radionuclide backgrounds can be used in accordance with the provisions of the treaty (such as event screening criteria in Annex 2 to the Protocol of the Treaty) for the effective implementation of the verification regime. Fission-based production of (99)Mo for medical purposes also generates nuisance radioxenon isotopes that are usually vented to the atmosphere. One of the ways to account for the effect emissions from medical isotope production has on radionuclide samples from the IMS is to use stack monitoring data, if they are available, and atmospheric transport modeling. Recently, individuals from seven nations participated in a challenge exercise that used atmospheric transport modeling to predict the time-history of (133)Xe concentration measurements at the IMS radionuclide station in Germany using stack monitoring data from a medical isotope production facility in Belgium. Participants received only stack monitoring data and used the atmospheric transport model and meteorological data of their choice. Some of the models predicted the highest measured concentrations quite well. A model comparison rank and ensemble analysis suggests that combining multiple models may provide more accurate predicted concentrations than any single model. None of the submissions based only on the stack monitoring data predicted the small measured concentrations very well. Modeling of sources by other nuclear facilities with smaller releases than medical isotope production facilities may be important in understanding how to discriminate those releases from

  7. End point prick test: could this new test be used to predict the outcome of oral food challenge in children with cow's milk allergy?

    Directory of Open Access Journals (Sweden)

    Bellini Federica

    2011-11-01

    Full Text Available Abstract Background Cow's milk allergy (CMA is the most frequent food allergy in childhood; the trend of CMA is often characterized by a progressive improvement to achieve tolerance in the first 4 to 5 years of life. It has been observed that specific IgE (sIgE towards cow's milk proteins decrease when the age increases. Although food allergy can be easily diagnosed, it is difficult to predict the outcome of the oral food challenge (OFC, that remains the gold standard in the diagnosis of food allergy, by allergometric tests. Methods We considered 44 children with CMA diagnosed through OFC who returned to our Allergy and Immunology Pediatric Department between January to December 2010 to evaluate the persistence of allergy or the achievement of tolerance. On the basis of the history, we performed both allergometric skin tests and OFC in children that were still following a milk-free diet, whereas only allergometric skin tests those that had already undergone spontaneous introduction of milk protein at home without presenting symptoms. Objective The aim of this study was to investigate the relationship between the persistence of CMA or the acquisition of tolerance and the results of the end point prick test (EPT. Results and Discussion The OFC with cow's milk was performed on 30 children, 4 children were excluded because of a history of severe reactions to cow's milk, and 10 because they had spontaneously already taken milk food derivates at home without problems. 16/30 (53% children showed clinical reactions and the challenge was stopped, 14/30 (47% did not have any reaction. Comparing the mean wheal diameter of every EPT's dilution between the group of allergic children and the tolerant ones, we obtained a significant difference (p We have also calculated sensitivity (SE, specificity (SP, the positive predictive value (PPV and the negative predictive value (NPV for each EPT dilution. Conclusions EPT is a safe and cheap test, easy to be executed

  8. Predictive validity of a MK-801-induced cognitive impairment model in mice: implications on the potential limitations and challenges of modeling cognitive impairment associated with schizophrenia preclinically.

    Science.gov (United States)

    Brown, Jordan W; Rueter, Lynne E; Zhang, Min

    2014-03-01

    Cognitive impairment associated with schizophrenia (CIAS) is a major and disabling symptom domain of the disease that is generally unresponsive to current pharmacotherapies. Critically important to the discovery of novel therapeutics for CIAS is the utilization of preclinical models with robust predictive validity. We investigated the predictive validity of MK-801-induced memory impairments in mouse inhibitory avoidance (MK-IA) as a preclinical model for CIAS by investigating compounds that have been tested in humans, including antipsychotics, sodium channel blocker mood stabilizers, and putative cognitive enhancers. The atypical antipsychotic clozapine, as well as risperidone and olanzapine (see Brown et al., 2013), had no effect on MK-801-induced memory impairments. For sodium channel blockers, carbamazepine significantly attenuated memory impairments induced by MK-801, whereas lamotrigine had no effect. Nicotine, donepezil, modafinil, and xanomeline all significantly attenuated MK-801-induced memory impairments, but the magnitude of effects and the dose-responses observed varied across compounds. Clinically, only acute administration of nicotine has demonstrated consistent positive effects on CIAS, while inconsistent results have been reported for lamotrigine, donepezil, and modafinil; atypical antipsychotics produce only moderate improvements at best. A positive clinical signal has been observed with xanomeline, but only in a small pilot trial. The results presented here suggest that the MK-IA model lacks robust predictive validity for CIAS as the model is likely permissive and may indicate false positive signals for compounds and mechanisms that lack clear clinical efficacy for CIAS. Our findings also highlight the potential limitations and challenges of using NMDA receptor antagonists in rodents to model CIAS. PMID:24269664

  9. Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

    Science.gov (United States)

    Unachukwu, Uchenna John; Warren, Alice; Li, Ze; Mishra, Shawn; Zhou, Jing; Sauane, Moira; Lim, Hyungsik; Vazquez, Maribel; Redenti, Stephen

    2016-03-01

    To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

  10. Responses to microbial challenges by SLAMF receptors

    Directory of Open Access Journals (Sweden)

    Boaz Job Van Driel

    2016-01-01

    Full Text Available The SLAMF Family (SLAMF of cell surface glycoproteins is comprised of nine glycoproteins and whilst SLAMF1, 3, 5, 6, 7, 8, 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other. Their interactions induce signal transduction networks in trans, thereby shaping immune cell-cell communications. Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development and, T and B cell responses to microbes and parasites. In addition, several SLAMF receptors serve as microbial sensors, which either positively or negatively modulate the function of macrophages, dendritic cells, neutrophils and NK cells in response to microbial challenges. The SLAMF receptor-microbe interactions contribute both to intracellular microbicidal activity as well as to migration of phagocytes to the site of inflammation. In this review, we describe the current knowledge on how the SLAMF receptors and their specific adapters SAP and EAT-2 regulate innate and adaptive immune responses to microbes.

  11. Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors

    DEFF Research Database (Denmark)

    Nguyen, E.D.; Meiler, J.; Norn, C.; Frimurer, T.M.

    2013-01-01

    The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs) creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual...... screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone and...... identification of correct ligand-receptor interactions. On average, top ranked receptor models built on template structures over 50% sequence identity are within 2.9 Å of the experimental structure, with an average root mean square deviation (RMSD) of 2.2 Å for the transmembrane region and 5 Å for the second...

  12. KiDoQ: using docking based energy scores to develop ligand based model for predicting antibacterials

    Directory of Open Access Journals (Sweden)

    Tewari Rupinder

    2010-03-01

    Full Text Available Abstract Background Identification of novel drug targets and their inhibitors is a major challenge in the field of drug designing and development. Diaminopimelic acid (DAP pathway is a unique lysine biosynthetic pathway present in bacteria, however absent in mammals. This pathway is vital for bacteria due to its critical role in cell wall biosynthesis. One of the essential enzymes of this pathway is dihydrodipicolinate synthase (DHDPS, considered to be crucial for the bacterial survival. In view of its importance, the development and prediction of potent inhibitors against DHDPS may be valuable to design effective drugs against bacteria, in general. Results This paper describes a methodology for predicting novel/potent inhibitors against DHDPS. Here, quantitative structure activity relationship (QSAR models were trained and tested on experimentally verified 23 enzyme's inhibitors having inhibitory value (Ki in the range of 0.005-22(mM. These inhibitors were docked at the active site of DHDPS (1YXD using AutoDock software, which resulted in 11 energy-based descriptors. For QSAR modeling, Multiple Linear Regression (MLR model was engendered using best four energy-based descriptors yielding correlation values R/q2 of 0.82/0.67 and MAE of 2.43. Additionally, Support Vector Machine (SVM based model was developed with three crucial descriptors selected using F-stepping remove-one approach, which enhanced the performance by attaining R/q2 values of 0.93/0.80 and MAE of 1.89. To validate the performance of QSAR models, external cross-validation procedure was adopted which accomplished high training/testing correlation values (q2/r2 in the range of 0.78-0.83/0.93-0.95. Conclusions Our results suggests that ligand-receptor binding interactions for DHDPS employing QSAR modeling seems to be a promising approach for prediction of antibacterial agents. To serve the experimentalist to develop novel/potent inhibitors, a webserver "KiDoQ" has been developed http

  13. Challenging the state-of-the-art in protein structure prediction: Highlights of experimental target structures for the 10th Critical Assessment of Techniques for Protein Structure Prediction Experiment CASP10

    OpenAIRE

    Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J. Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V; Craig, Timothy K.; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut

    2014-01-01

    For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, over 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this paper, authors of some of the most ...

  14. Progress and challenges in the computational prediction of gene function using networks [v1; ref status: indexed, http://f1000r.es/SqmJUM

    Directory of Open Access Journals (Sweden)

    Paul Pavlidis

    2012-09-01

    Full Text Available In this opinion piece, we attempt to unify recent arguments we have made that serious confounds affect the use of network data to predict and characterize gene function. The development of computational approaches to determine gene function is a major strand of computational genomics research. However, progress beyond using BLAST to transfer annotations has been surprisingly slow. We have previously argued that a large part of the reported success in using "guilt by association" in network data is due to the tendency of methods to simply assign new functions to already well-annotated genes. While such predictions will tend to be correct, they are generic; it is true, but not very helpful, that a gene with many functions is more likely to have any function. We have also presented evidence that much of the remaining performance in cross-validation cannot be usefully generalized to new predictions, making progressive improvement in analysis difficult to engineer. Here we summarize our findings about how these problems will affect network analysis, discuss some ongoing responses within the field to these issues, and consolidate some recommendations and speculation, which we hope will modestly increase the reliability and specificity of gene function prediction.

  15. Moderation of Stimulus Material on the Prediction of IQ with Infants' Performance in the Visual Expectation Paradigm: Do Greebles Make the Task More Challenging?

    Science.gov (United States)

    Teubert, Manuel; Lohaus, Arnold; Fassbender, Ina; Vöhringer, Isabel A.; Suhrke, Janina; Poloczek, Sonja; Freitag, Claudia; Lamm, Bettina; Teiser, Johanna; Keller, Heidi; Knopf, Monika; Schwarzer, Gudrun

    2015-01-01

    The objective of this study was to examine the role of the stimulus material for the prediction of later IQ by early learning measures in the Visual Expectation Paradigm (VExP). The VExP was assessed at 9?months using two types of stimuli, Greebles and human faces. Greebles were assumed to be associated with a higher load on working memory in…

  16. Localization of Wnt1 and Frizzled 2 and identification of their ligand-receptor relationship in the ovary tissue of immature mice%Wnt1和Frizzled2在性成熟前小鼠卵巢组织织定位及配受体关系鉴定

    Institute of Scientific and Technical Information of China (English)

    庞训胜; 林春联; 许雪萍; 王正朝

    2011-01-01

    In order to reveal the mechanism of Wnt1 and Frizzled (Fzd) 2 in the regulation of ovarian and follicular development, twelve 3-week old mice were used to investigate the localization of Wnt1 and Fzd2 in the ovary by immunohistochemistry (IHC) and their ligand-receptor relationship by coimmunoprecipitation (Co-IP). The results showed that a strong immunostaining of Wnt1 was found in the cytoplasm and on the member of oocytes of health primary and secondary follicles, as well as that in the granular cells near basal lamina of preantral and antral follicles, however Fzd2 staining was found only in the cytoplasm. There was weakly immunostaining of Wnt1 in granular cells around antrum and cumulus oophorus around zona pellucida. The elongated stromal cells round developing follicles or branched from ovarian cores were immunostained by Wnt1 and Fzd2. Furthermore, some scattered cells were also immunostained in the interstitial gland, while in the oocytes of follicular atresia, a strong and asymmetrical immunostaining was also found. Co-IP analysis showed that there was a direct interaction between Fzd2 and Wnt1 in the ovarian oocytes. Together, the results over clearly demonstrated the expression and localization of Wnt1 and Fzd2 in a cell-specific manner and their ligand-receptor relation,implying the important roles during ovarian follicular development.%为揭示Wnt1和Frizzled(Fzd)2参与卵巢和卵泡发育的作用机制,选择12只3周龄小鼠,应用免疫组化研究Wnt1和Fzd2在卵巢组织内的定位,免疫共沉淀鉴定其蛋白间的配受体关系.结果表明:在健康初级、次级卵泡卵母细胞以及腔前和腔后卵泡近基膜颗粒细胞的胞质和胞膜中,Wnt1均表现较强的免疫染色,Fzd2在胞质内免疫染色;在卵泡腔周围颗粒细胞和透明带周围卵丘细胞中Wnt1免疫染色弱;从卵巢中心扩展或环绕生长卵泡的条形基质细胞中Wnt1和Fzd2免疫染色阳性,间质腺存在免疫染色细胞;在

  17. International Challenge to Predict the Impact of Radioxenon Releases from Medical Isotope Production on a Comprehensive Nuclear Test Ban Treaty Sampling Station

    Energy Technology Data Exchange (ETDEWEB)

    Eslinger, Paul W.; Bowyer, Ted W.; Achim, Pascal; Chai, T.; Deconninck, Benoit; Freeman, Katie; Generoso, Sylvia; Hayes, Philip; Heidmann, Verena; Hoffman, Ian; Kijima, Yuichi; Krysta, Monika; Malo, Alain; Maurer, Christian; Ngan, Fantine; Robins, Peter; Ross, J. Ole; Saunier, Olivier; Schlosser, Clemens; Schoeppner, Michael; Schrom, Brian T.; Seibert, P.; Stein, Ariel; Ungar, Kurt; Yi, Jing

    2016-03-01

    Abstract The International Monitoring System (IMS) is part of the verification regime for the Comprehensive Nuclear-Test-Ban-Treaty Organization (CTBTO). At entry-into-force, half of the 80 radionuclide stations will be able to measure concentrations of several radioactive xenon isotopes produced in nuclear explosions, and then the full network may be populated with xenon monitoring afterward (Bowyer et al., 2013). Fission-based production of 99Mo for medical purposes also releases radioxenon isotopes to the atmosphere (Saey, 2009). One of the ways to mitigate the effect of emissions from medical isotope production is the use of stack monitoring data, if it were available, so that the effect of radioactive xenon emissions could be subtracted from the effect from a presumed nuclear explosion, when detected at an IMS station location. To date, no studies have addressed the impacts the time resolution or data accuracy of stack monitoring data have on predicted concentrations at an IMS station location. Recently, participants from seven nations used atmospheric transport modeling to predict the time-history of 133Xe concentration measurements at an IMS station in Germany using stack monitoring data from a medical isotope production facility in Belgium. Participants received only stack monitoring data and used the atmospheric transport model and meteorological data of their choice. Some of the models predicted the highest measured concentrations quite well (a high composite statistical model comparison rank or a small mean square error with the measured values). The results suggest release data on a 15 min time spacing is best. The model comparison rank and ensemble analysis suggests that combining multiple models may provide more accurate predicted concentrations than any single model. Further research is needed to identify optimal methods for selecting ensemble members and those methods may depend on the specific transport problem. None of the submissions based only

  18. Climate prediction and predictability

    Science.gov (United States)

    Allen, Myles

    2010-05-01

    Climate prediction is generally accepted to be one of the grand challenges of the Geophysical Sciences. What is less widely acknowledged is that fundamental issues have yet to be resolved concerning the nature of the challenge, even after decades of research in this area. How do we verify or falsify a probabilistic forecast of a singular event such as anthropogenic warming over the 21st century? How do we determine the information content of a climate forecast? What does it mean for a modelling system to be "good enough" to forecast a particular variable? How will we know when models and forecasting systems are "good enough" to provide detailed forecasts of weather at specific locations or, for example, the risks associated with global geo-engineering schemes. This talk will provide an overview of these questions in the light of recent developments in multi-decade climate forecasting, drawing on concepts from information theory, machine learning and statistics. I will draw extensively but not exclusively from the experience of the climateprediction.net project, running multiple versions of climate models on personal computers.

  19. Challenges in predicting the need for coronary artery bypass grafting at presentation in patients with non-ST-segment elevation acute coronary syndromes.

    Science.gov (United States)

    Mehta, Rajendra H; Chen, Anita Y; Pollack, Charles V; Roe, Matthew T; Zalenski, Robert J; Clements, Elizabeth A; Gibler, W Brian; Ohman, E Magnus; Harrington, Robert A; Peterson, Eric D

    2006-09-01

    In the case of non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), the acute use of certain antiplatelet agents is complicated by concerns about perioperative bleeding risks in patients requiring coronary artery bypass grafting (CABG) during the index hospitalization. As a result, clinicians often withhold potentially useful agents, such as clopidogrel, before determining patients' coronary anatomy. An accurate predictive model could allow for a better balance of this safety concern with the demonstrated benefits of agents such as clopidogrel. To create an accurate decision-making tool that would assess, at hospital presentation, the need for CABG in patients with NSTE-ACSs, we studied 61,974 high-risk patients with NSTE-ACS admitted to 311 CABG-capable hospitals participating in Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) from 2001 to 2003. A total of 8,395 patients (14%) underwent CABG during their initial hospital stay. A multivariate model was developed and identified 13 presenting clinical characteristics significantly associated with the likelihood of CABG (previous CABG, male gender, previous heart failure, diabetes, hyperlipidemia, renal insufficiency, ST depression and transient ST elevation, age > or = 75 years, previous percutaneous coronary intervention, family history of coronary artery disease, hypertension, trends in CABG rates, and previous stroke). This model had only modest predictive accuracy and calibration (c-index = 0.67). In conclusion, although certain presenting clinical features are associated with an increased likelihood of CABG in patients with NSTE-ACSs during the index hospitalization, it remains difficult to reliably identify, before diagnostic angiography, those who will subsequently undergo surgical revascularization. PMID:16923449

  20. Challenges of predicting the potential distribution of a slow-spreading invader: a habitat suitability map for an invasive riparian tree

    Science.gov (United States)

    Jarnevich, Catherine S.; Reynolds, Lindsay V.

    2011-01-01

    Understanding the potential spread of invasive species is essential for land managers to prevent their establishment and restore impacted habitat. Habitat suitability modeling provides a tool for researchers and managers to understand the potential extent of invasive species spread. Our goal was to use habitat suitability modeling to map potential habitat of the riparian plant invader, Russian olive (Elaeagnus angustifolia). Russian olive has invaded riparian habitat across North America and is continuing to expand its range. We compiled 11 disparate datasets for Russian olive presence locations (n = 1,051 points and 139 polygons) in the western US and used Maximum entropy (Maxent) modeling to develop two habitat suitability maps for Russian olive in the western United States: one with coarse-scale water data and one with fine-scale water data. Our models were able to accurately predict current suitable Russian olive habitat (Coarse model: training AUC = 0.938, test AUC = 0.907; Fine model: training AUC = 0.923, test AUC = 0.885). Distance to water was the most important predictor for Russian olive presence in our coarse-scale water model, but it was only the fifth most important variable in the fine-scale model, suggesting that when water bodies are considered on a fine scale, Russian olive does not necessarily rely on water. Our model predicted that Russian olive has suitable habitat further west from its current distribution, expanding into the west coast and central North America. Our methodology proves useful for identifying potential future areas of invasion. Model results may be influenced by locations of cultivated individuals and sampling bias. Further study is needed to examine the potential for Russian olive to invade beyond its current range. Habitat suitability modeling provides an essential tool for enhancing our understanding of invasive species spread.

  1. Predicting workload profiles of brain-robot interface and electromygraphic neurofeedback with cortical resting-state networks: personal trait or task-specific challenge?

    Science.gov (United States)

    Fels, Meike; Bauer, Robert; Gharabaghi, Alireza

    2015-08-01

    Objective. Novel rehabilitation strategies apply robot-assisted exercises and neurofeedback tasks to facilitate intensive motor training. We aimed to disentangle task-specific and subject-related contributions to the perceived workload of these interventions and the related cortical activation patterns. Approach. We assessed the perceived workload with the NASA Task Load Index in twenty-one subjects who were exposed to two different feedback tasks in a cross-over design: (i) brain-robot interface (BRI) with haptic/proprioceptive feedback of sensorimotor oscillations related to motor imagery, and (ii) control of neuromuscular activity with feedback of the electromyography (EMG) of the same hand. We also used electroencephalography to examine the cortical activation patterns beforehand in resting state and during the training session of each task. Main results. The workload profile of BRI feedback differed from EMG feedback and was particularly characterized by the experience of frustration. The frustration level was highly correlated across tasks, suggesting subject-related relevance of this workload component. Those subjects who were specifically challenged by the respective tasks could be detected by an interhemispheric alpha-band network in resting state before the training and by their sensorimotor theta-band activation pattern during the exercise. Significance. Neurophysiological profiles in resting state and during the exercise may provide task-independent workload markers for monitoring and matching participants’ ability and task difficulty of neurofeedback interventions.

  2. Nanopore-Based Sensors for Ligand-Receptor Lead Optimization.

    Science.gov (United States)

    Luan, Binquan; Huynh, Tien; Zhou, Ruhong

    2015-02-01

    Developing a low-cost and high-efficacy method to optimize prescreened or designed drug candidates will facilitate drug discovery and biomedical research in general. Current methods of drug screening usually involve tedious sample preparation and costly biological/chemical assays. Here, through all-atom molecular dynamics simulations, we propose a new drug optimization method, based on the nanopore force spectroscopy, to electrically detect the binding strength between a drug molecule and a target protein. Simulation results demonstrate that the drug-protein complex can be electrophoretically driven into a nanopore, which is followed by the rupture of the complex at a critical biasing voltage. The latter determines the binding strength of the tested drug molecule. It is expected that the application of this single-molecule technology could help to accelerate the drug discovery, particularly for processes of the narrow screening and further lead optimization. PMID:26261942

  3. The radio ligand receptor assay for thyroid stimulating factors

    International Nuclear Information System (INIS)

    The possible uses of RRA in routine examinations to detect HTSI and physiological TSH concentrations were investigated in this study. The primary difficulties were that the RRA had a low sensitivity using the Mehdi method and the investigation results exhibited large deviations. The authors first investigated the non-specific influences of the incubation medium such as temperature, incubation time, protein used and salts on the 125I-TSH compared by means of the enriched membrane according to Mehdi. After the modification of the labelling process of 125I-TSH with Smith's post-purification method, it was possible to improve the sensitivity of the assay system from 100 μU to 10 μU TSH/test. It was now possible to detect HTSI in 67% of the Morbus Basedow sera in clinical tests (compared with 54% in the RRA prior to modification and 19% in the McKenzie assay). The discrepancy between these results and those of Mukhtar et al. - with a HTSI detection in 100% of the cases investigated for the same sensitivity of the assay - remains unexplained. The sensitivity of the RRA is not sufficient to detect TSH in serum, as the standard region for the basal TSH level in the serum is given as between 0.5 and 3.8 μU/ml in the radioimmunoassay. (orig./AJ)

  4. Featherweight Challenge

    Science.gov (United States)

    Love, Tyler S.; Ryan, Larry

    2012-01-01

    As science, technology education, and engineering programs suffer budget cuts, educators continue to seek cost-effective activities that engage students and reinforce standards. The featherweight challenge is a hands-on activity that challenges students to continually refine their design while not breaking the budget. This activity uses one of the…

  5. Neural system prediction and identification challenge

    OpenAIRE

    Ioannis eVlachos; Zaytsev, Yury V.; Sebastian eSpreizer; Ad eAertsen; Arvind eKumar

    2013-01-01

    Can we infer the function of a biological neural network (BNN) if we know the connectivity and activity of all its constituent neurons? This question is at the core of neuroscience and, accordingly, various methods have been developed to record the activity and connectivity of as many neurons as possible. Surprisingly, there is no theoretical or computational demonstration that neuronal activity and connectivity are indeed sufficient to infer the function of a BNN. Therefore, we pose the Neur...

  6. Challenges of Student Selection: Predicting Academic Performance

    Science.gov (United States)

    van der Merwe, D.; de Beer, M.

    2006-01-01

    Finding accurate predictors of tertiary academic performance, specifically for disadvantaged students, is essential because of budget constraints and the need of the labour market to address employment equity. Increased retention, throughput and decreased dropout rates are vital. When making admission decisions, the under preparedness of students…

  7. Meeting the Challenge

    Directory of Open Access Journals (Sweden)

    T. Reg Bott

    2009-01-01

    Full Text Available The first Chempor Conference held in Lisbon in 1975 under the auspices of the Calouste Gulbenkian Foundation, heralded a regular wide-ranging review of research and development in Portugal and the UK Progressively in later years the Conferences have attracted contributions from other European countries and indeed further afield. There is an increasing awareness of the problems for the environment, notably global warming, brought about by human activities. Recent predictions about the future are dire, particularly regarding food and water for a rapidly growing world population. They represent a substantial challenge to the scientific and technical fraternity. In response to that challenge it is important to keep up to date with technical developments, to meet and keep in touch with coworkers in associated fields, and to cooperate wherever possible. The papers presented at the Chempor and other conferences have made and continue to make a significant contribution to that objective of meeting the challenge.

  8. Logistical challenges

    Directory of Open Access Journals (Sweden)

    Steve Matthews

    2005-07-01

    Full Text Available The impact of the Asian tsunami was unprecedented and the logistical challenges of meeting the needs of those affected were enormous. Had the tsunami happened even five years ago, World Vision would not have been able to respond nearly as effectively as it did.

  9. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part of th...

  10. Ethical Challenges

    Science.gov (United States)

    Morris, Michael

    2004-01-01

    All evaluators face the challenge of striving to adhere to the highest possible standards of ethical conduct. Translating the AEA's Guiding Principles and the Joint Committee's Program Evaluation Standards into everyday practice, however, can be a complex, uncertain, and frustrating endeavor. Moreover, acting in an ethical fashion can require…

  11. Editorial Challenges

    OpenAIRE

    Budin, Wendy C.

    2008-01-01

    In this column, the editor of The Journal of Perinatal Education (JPE) discusses some of the challenges involved in becoming the new editor of JPE. The editor also describes the contents of this issue, which offer a broad range of resources, research, and inspiration for childbirth educators in their efforts to promote normal birth.

  12. Archiving challenges

    OpenAIRE

    Ringersma, J.

    2010-01-01

    Teaching slides on: What is a digital archive? Parties involved in digital archiving Archiving challenges organization of data coherence and persistency access and safety Language archiving software Different users, different needs For: Saami Language Documentation and Revitalization. Winter school, Bodø, Norway

  13. CHALLENGES IN BRONCHIAL CHALLENGE TESTING

    NARCIS (Netherlands)

    Lexmond, A. J.; Hagedoorn, P.; Frijlink, H. W.; de Boer, A. H.

    2013-01-01

    Background: In the adenosine 5'-monophosphate (AMP) bronchial challenge test, AMP is usually administered according to dosing protocols developed for histamine/methacholine. It has never been thoroughly investigated whether these protocols are suitable for AMP as well. Methods: The setup of the two-

  14. Accepted: 2008-11-05Delivery and immunologic efficacy of CpG ODN targeting B lymphocytes of umbilical cord blood by CD40 ligand-receptor-mediated carrier%CD40配体-受体载体介导的CpG ODN靶向脐血B淋巴细胞的特异传递及其免疫效应

    Institute of Scientific and Technical Information of China (English)

    曾慧兰; 蒋建伟; 郑梅珍; 古晨; 韩新爱; 曾耀英; 狄静芳; 严玉霞

    2009-01-01

    cells and degradation by nuclease blocks its clinical application. OBJECTIVE: To explore the specific delivery and its immunologic efficacy of CpG ODN targeting B lymphocytes of umbilical cord blood by CD40 ligand-receptor-mediated carrier system. DESIGN, TIME AND SETTING: An observation and control experiment was performed at the Department of Hematology, and Department of Pediatric, the First Affiliated Hospital of Jinan University from April 2004 to October 2007. MATERIALS: Fresh umbilical cord blood with heparin was obtained from healthy, natal infant. Informed consent was obtained from his parents, and the experiment was approved by the hospital Ethics Committee. METHODS: CD40 ligand (CD40L)-EDC-PLL-CpG ODN conjugated complex was prepared. Mononuclear cells (MNCs) from umbilical cord blood were co-cultured with conjugated complexes. Uptake rate, mean fluorescence intensity of FAM marked CpG ODN, expressions of MNCs, proliferations of lymphocytes and the IgG levels of culture supematants were detected by flow cytometry, fluorescence techniques, MTT assay and ELISA, respectively. MAIN OUTCOME MEASURES: The uptake rate, the mean fluorescence intensity of CpG ODN by MNCs, subgroups and proliferations of lymphocytes, and IgG levels of culture supematants. RESULTS: Compared to the pure CpG ODN group, the uptake rate of the conjugated complexes group was higher (98%), the peak level of up-taking occurred earlier, and intracellular fluorescence intensity maintained much more stable. Expressions of CD19+, CD22+, and CD20+ was increased, A value and IgG levels in supematants were all higher than that of the control group. CONCLUSION: CD40 tigand-receptor-mediated carrier system is helpful for CpG ODN delivery targeting to B lymphocyte, enhancing its immunological efficiency.

  15. Global challenges

    International Nuclear Information System (INIS)

    A major challenge now facing the world is the supply of energy needed for growth and development in a manner which is not only economically viable but also environmentally acceptable and sustainable in view of the demands of and risks to future generations. The internationally most significant pollutants from energy production through fossil fuels are SO2 and NOx which cause acid rain, and CO2 which is the most significant contributor to the greenhouse effect. Nuclear power, now providing about 17% of the world's electricity and 5% of the primary energy already is making a notable contribution to avoiding these emissions. While the industrialized countries will need more energy and especially electricity in the future, the needs of the developing countries are naturally much larger and present a tremendous challenge to the shaping of the world's future energy supply system. The advanced countries will have to accept special responsibilities, as they can most easily use advanced technologies and they have been and remain the main contributors to the environmental problems we now face. Energy conservation and resort to new renewable energy sources, though highly desirable, appear inadequate alone to meet the challenges. The world can hardly afford to do without an increased use of nuclear power, although it is strongly contested in many countries. The objections raised against the nuclear option focus on safety, waste management and disposal problems and the risk for proliferation of nuclear weapons. These issues are not without their problems. The risk of proliferation exists but will not appreciably diminish with lesser global reliance on nuclear power. The waste issue is more of a political than a technical problem. The use of nuclear power, or any other energy source, will never be at zero risk, but the risks are constantly reduced by new techniques and practices. The IAEA sees it as one of its priority tasks to promote such techniques. (author)

  16. Data Challenges

    CERN Multimedia

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  17. Towards predictive docking at aminergic G-protein coupled receptors.

    Science.gov (United States)

    Jakubík, Jan; El-Fakahany, Esam E; Doležal, Vladimír

    2015-11-01

    G protein-coupled receptors (GPCRs) are hard to crystallize. However, attempts to predict their structure have boomed as a result of advancements in crystallographic techniques. This trend has allowed computer-aided molecular modeling of GPCRs. We analyzed the performance of four molecular modeling programs in pose evaluation of re-docked antagonists / inverse agonists to 11 original crystal structures of aminergic GPCRs using an induced fit-docking procedure. AutoDock and Glide were used for docking. AutoDock binding energy function, GlideXP, Prime MM-GB/SA, and YASARA binding function were used for pose scoring. Root mean square deviation (RMSD) of the best pose ranged from 0.09 to 1.58 Å, and median RMSD of the top 60 poses ranged from 1.47 to 3.83 Å. However, RMSD of the top pose ranged from 0.13 to 7.33 Å and ranking of the best pose ranged from the 1st to 60th out of 60 poses. Moreover, analysis of ligand-receptor interactions of top poses revealed substantial differences from interactions found in crystallographic structures. Bad ranking of top poses and discrepancies between top docked poses and crystal structures render current simple docking methods unsuitable for predictive modeling of receptor-ligand interactions. Prime MM-GB/SA optimized for 3NY9 by multiple linear regression did not work well at 3NY8 and 3NYA, structures of the same receptor with different ligands. However, 9 of 11 trajectories of molecular dynamics simulations by Desmond of top poses converged with trajectories of crystal structures. Key interactions were properly detected for all structures. This procedure also worked well for cross-docking of tested β2-adrenergic antagonists. Thus, this procedure represents a possible way to predict interactions of antagonists with aminergic GPCRs. PMID:26453085

  18. SPS Challenges

    CERN Document Server

    Chapochnikova, Elena

    2008-01-01

    In future the SPS should be able to transfer to the LHC the beam produced by a completely new pre-injector chain and required by the LHC for different upgrade scenarios. The issues related to this extremely challenging task are presented together with some possible ways of overcoming the problems that arise. Besides an increase in injection energy provided by PS2, these measures can include both an SPS vacuum chamber upgrade against the e-cloud and operation with larger longitudinal emittance for beam stability. As a result the power plant of the SPS RF system must be doubled. The SPS upgrade will also need the improvement or replacement of many other machine elements.

  19. Climate change challenges for SEA

    DEFF Research Database (Denmark)

    Larsen, Sanne Vammen

    This paper takes a theoretical perspective on the challenges that climate changes pose for SEA. The theoretical framework used is the sociologist Ulrich Beck’s theory of risk society and the aspects that characterise this society. Climate change is viewed as a risk, and the theory is used to derive...... two challenges for the practice of SEA: delivering assessments and predictions; and handling differences in opinion and debate. Based on empirical evidence from document studies and interviews, the paper discusses the reflection of these theoretical challenges in practice....

  20. Challenges of operational river forecasting

    OpenAIRE

    T. C. Pagano; Wood, A.W.; Ramos, M.H.; H. L. Cloke; Pappenbreger, F.; Verkade, J. S.; et al, ...

    2014-01-01

    Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1)making themost of available data, 2)making accurate predictio...

  1. Challenges of operational river forecasting

    OpenAIRE

    T. C. Pagano; Wood, A.W.; Ramos, M.H.; H. L. Cloke; Pappenberger, F.; Clark, M. P.; Cranston, M.; Kavetski, D.; T. Mathevet; Sorooshian, S; Verkade, J. S.

    2014-01-01

    Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate ...

  2. Seven challenges for neuroscience.

    Science.gov (United States)

    Markram, Henry

    2013-01-01

    Although twenty-first century neuroscience is a major scientific enterprise, advances in basic research have not yet translated into benefits for society. In this paper, I outline seven fundamental challenges that need to be overcome. First, neuroscience has to become "big science" - we need big teams with the resources and competences to tackle the big problems. Second, we need to create interlinked sets of data providing a complete picture of single areas of the brain at their different levels of organization with "rungs" linking the descriptions for humans and other species. Such "data ladders" will help us to meet the third challenge - the development of efficient predictive tools, enabling us to drastically increase the information we can extract from expensive experiments. The fourth challenge goes one step further: we have to develop novel hardware and software sufficiently powerful to simulate the brain. In the future, supercomputer-based brain simulation will enable us to make in silico manipulations and recordings, which are currently completely impossible in the lab. The fifth and sixth challenges are translational. On the one hand we need to develop new ways of classifying and simulating brain disease, leading to better diagnosis and more effective drug discovery. On the other, we have to exploit our knowledge to build new brain-inspired technologies, with potentially huge benefits for industry and for society. This leads to the seventh challenge. Neuroscience can indeed deliver huge benefits but we have to be aware of widespread social concern about our work. We need to recognize the fears that exist, lay them to rest, and actively build public support for neuroscience research. We have to set goals for ourselves that the public can recognize and share. And then we have to deliver on our promises. Only in this way, will we receive the support and funding we need. PMID:24139651

  3. Scrapheap Challenge

    CERN Multimedia

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  4. Energetic challenges

    International Nuclear Information System (INIS)

    Full text: Connecting the 2 billion people who have no access to commercial energy is the most important energy challenge facing the world community. Women and children, primarily in developing countries, spend their days collecting wood or cow dung for fuel for cooking and heating their homes in very inefficient stoves: this both harms the environment and directly threatens the health of their families. Outmoded boilers linked to central heating systems in most of the cities of Eastern Europe and the former Soviet Union pose another challenge. They are inefficient; they lack modern pollution control; and the end use of the heat is not metered, leading to more inefficiency and waste. Both of these problems cry out to the world for investment. Investing in energy solutions in these countries can bring about significant and immediate local environmental improvements, achieve greatly improved energy efficiency, and substantially reduce greenhouse gas emissions. But, energy and environmental policy tends to direct investment towards industrial countries, even though it would have a greater impact on the environment - not to mention the human condition in general - in the developing countries and transition economies. We need a new direction in energy policy. The World Energy Council has studied the needs and we believe a number of our proposed policy recommendations would lead towards greater investment in the countries where it is most needed. The political risk of key energy project investments must be addressed both by the countries seeking outside investment and by the global community at large. The countries must create an investor-friendly climate, which includes the rule of law and recognizes private property rights. The global community can contribute by developing new political risk insurance schemes rewarding the countries that create this climate. Energy must be priced to cover costs and ensure payment. In too many countries, blanket subsidies for energy

  5. Regulatory challenges

    International Nuclear Information System (INIS)

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for the

  6. Energy challenges

    International Nuclear Information System (INIS)

    Satisfying the world's insatiable appetite for fuel without destroying the environment is the biggest challenge facing the energy industry. World energy consumption is expected to soar by 50% to a staggering 180 000 GW h per year by 2020, with the developing world demanding an ever-increasing share. Although oil and natural-gas reserves will last for several more decades, environmental concerns are increasingly dominating the agenda. Last year 178 countries agreed to a watered-down version of the original Kyoto protocol, which was designed to reduce the emissions of greenhouse gases from industrialized countries by an average of 5.2% below 1990 levels. Under the new agreement, dubbed 'Kyoto lite' by environmentalists, emissions will be cut by just 2%. The relaxed targets are still not enough to convince the US, the world's biggest polluter, to sign the Kyoto treaty. Renewable technologies still make up less than 1% of the world's commercial energy. Distributed power is also likely to emerge from the development of fuel cells - devices that convert the chemical energy of hydrogen and oxygen directly into electricity, with only water as a by-product. The move away from carbon-based fossil fuels to hydrogen is also driving the hydrogen economy. A longer-term possibility is nuclear fusion. Despite the enormous progress in the performance of experiments over the past 30 years, nuclear fusion is still decades away from generating electricity. Advocates of fusion power claim that it could be a safe and sustainable source of energy that does not produce any greenhouse gases or long-lived nuclear waste. However, physicists have still to demonstrate that the energy produced by the fusion of deuterium and tritium can be sustained. Advances in physics and engineering are making energy from renewable sources increasingly affordable. But political will - as well as scientific progress - is just as crucial for safeguarding the environment for generations to come

  7. HEPEX - achievements and challenges!

    Science.gov (United States)

    Pappenberger, Florian; Ramos, Maria-Helena; Thielen, Jutta; Wood, Andy; Wang, Qj; Duan, Qingyun; Collischonn, Walter; Verkade, Jan; Voisin, Nathalie; Wetterhall, Fredrik; Vuillaume, Jean-Francois Emmanuel; Lucatero Villasenor, Diana; Cloke, Hannah L.; Schaake, John; van Andel, Schalk-Jan

    2014-05-01

    HEPEX is an international initiative bringing together hydrologists, meteorologists, researchers and end-users to develop advanced probabilistic hydrological forecast techniques for improved flood, drought and water management. HEPEX was launched in 2004 as an independent, cooperative international scientific activity. During the first meeting, the overarching goal was defined as: "to develop and test procedures to produce reliable hydrological ensemble forecasts, and to demonstrate their utility in decision making related to the water, environmental and emergency management sectors." The applications of hydrological ensemble predictions span across large spatio-temporal scales, ranging from short-term and localized predictions to global climate change and regional modeling. Within the HEPEX community, information is shared through its blog (www.hepex.org), meetings, testbeds and intercompaison experiments, as well as project reportings. Key questions of HEPEX are: * What adaptations are required for meteorological ensemble systems to be coupled with hydrological ensemble systems? * How should the existing hydrological ensemble prediction systems be modified to account for all sources of uncertainty within a forecast? * What is the best way for the user community to take advantage of ensemble forecasts and to make better decisions based on them? This year HEPEX celebrates its 10th year anniversary and this poster will present a review of the main operational and research achievements and challenges prepared by Hepex contributors on data assimilation, post-processing of hydrologic predictions, forecast verification, communication and use of probabilistic forecasts in decision-making. Additionally, we will present the most recent activities implemented by Hepex and illustrate how everyone can join the community and participate to the development of new approaches in hydrologic ensemble prediction.

  8. Homology Models of Melatonin Receptors: Challenges and Recent Advances

    Directory of Open Access Journals (Sweden)

    Silvia Rivara

    2013-04-01

    Full Text Available Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs, named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore models. The ability of these ligand-receptor complexes to rationalize structure-activity relationships of known series of melatonergic compounds will be commented upon.

  9. The conformational signature of β-arrestin2 predicts its trafficking and signalling functions.

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M; Strungs, Erik G; Kwon, Joshua Y; Morinelli, Thomas A; Peterson, Yuri K; Laporte, Stephane A; Luttrell, Louis M

    2016-03-31

    Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in β-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of β-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in β-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average β-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function. PMID:27007854

  10. National Drug IQ Challenge

    Science.gov (United States)

    ... Drug & Alcohol IQ Challenge 2016 National Drug & Alcohol IQ Challenge Get Started! Correct/Total Questions: Score: Other ... accessible version of the 2016 National Drug & Alcohol IQ Challenge , [PDF, 637KB]. Download an accessible version of ...

  11. Challenges in complex systems science

    Science.gov (United States)

    San Miguel, M.; Johnson, J. H.; Kertesz, J.; Kaski, K.; Díaz-Guilera, A.; MacKay, R. S.; Loreto, V.; Érdi, P.; Helbing, D.

    2012-11-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneous databases; moving from data to dynamical models, going beyond correlations to cause-effect relationships, understanding the relationship between simple and comprehensive models with appropriate choices of variables, ensemble modeling and data assimilation, modeling systems of systems of systems with many levels between micro and macro; and formulating new approaches to prediction, forecasting, and risk, especially in systems that can reflect on and change their behaviour in response to predictions, and systems whose apparently predictable behaviour is disrupted by apparently unpredictable rare or extreme events. These challenges are part of the FuturICT agenda.

  12. Robust Distributed Online Prediction

    CERN Document Server

    Dekel, Ofer; Shamir, Ohad; Xiao, Lin

    2010-01-01

    The standard model of online prediction deals with serial processing of inputs by a single processor. However, in large-scale online prediction problems, where inputs arrive at a high rate, an increasingly common necessity is to distribute the computation across several processors. A non-trivial challenge is to design distributed algorithms for online prediction, which maintain good regret guarantees. In \\cite{DMB}, we presented the DMB algorithm, which is a generic framework to convert any serial gradient-based online prediction algorithm into a distributed algorithm. Moreover, its regret guarantee is asymptotically optimal for smooth convex loss functions and stochastic inputs. On the flip side, it is fragile to many types of failures that are common in distributed environments. In this companion paper, we present variants of the DMB algorithm, which are resilient to many types of network failures, and tolerant to varying performance of the computing nodes.

  13. Developing a Watershed Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    This article presents a watershed challenge that gives students an opportunity to investigate the challenge of using a watershed area as a site for development, examining the many aspects of this multifaceted problem. This design challenge could work well in a team-based format, with students taking on specific aspects of the challenges and…

  14. Predicting helpful product reviews

    OpenAIRE

    O'Mahony, Michael P.; Cunningham, Pádraig; Smyth, Barry

    2010-01-01

    Millions of users are today posting user-generated content online, expressing their opinions on all manner of goods and services, topics and social affairs. While undoubtedly useful,user-generated content presents consumers with significant challenges in terms of information overload and quality considerations. In this paper, we address these issues in the context of product reviews and present a brief survey of our work to date on predicting review helpfulness. In particular, the performa...

  15. 78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

    Science.gov (United States)

    2013-08-13

    ... SPACE ADMINISTRATION Centennial Challenges 2014 Sample Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot... Robot Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  16. Challenges of Parenting Multiples

    Science.gov (United States)

    ... the American Society for Reproductive Medicine Challenges of Parenting Multiples There are many psychological, social, and economic ... the unique challenges and rewards that come from parenting multiples. For more information on the medical aspects ...

  17. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us ... Only Natural email updates. Enter email address Submit Home > It's Only Natural > Overcoming challenges Overcoming breastfeeding challenges ...

  18. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming breastfeeding challenges Dealing with lack of family support Is my baby getting enough milk? Breastfeeding ...

  19. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available A project of the U.S. Department of Health and Human Services Office on Women's Health Skip Navigation ... challenges Overcoming breastfeeding challenges Dealing with lack of family support Is my baby getting enough ...

  20. Operational Dust Prediction

    Science.gov (United States)

    Benedetti, Angela; Baldasano, Jose M.; Basart, Sara; Benincasa, Francesco; Boucher, Olivier; Brooks, Malcolm E.; Chen, Jen-Ping; Colarco, Peter R.; Gong, Sunlin; Huneeus, Nicolas; Jones, Luke; Lu, Sarah; Menut, Laurent; Morcrette, Jean-Jacques; Mulcahy, Jane; Nickovic, Slobodan; Garcia-Pando, Carlos P.; Reid, Jeffrey S.; Sekiyama, Thomas T.; Tanaka, Taichu Y.; Terradellas, Enric; Westphal, Douglas L.; Zhang, Xiao-Ye; Zhou, Chun-Hong

    2014-01-01

    Over the last few years, numerical prediction of dust aerosol concentration has become prominent at several research and operational weather centres due to growing interest from diverse stakeholders, such as solar energy plant managers, health professionals, aviation and military authorities and policymakers. Dust prediction in numerical weather prediction-type models faces a number of challenges owing to the complexity of the system. At the centre of the problem is the vast range of scales required to fully account for all of the physical processes related to dust. Another limiting factor is the paucity of suitable dust observations available for model, evaluation and assimilation. This chapter discusses in detail numerical prediction of dust with examples from systems that are currently providing dust forecasts in near real-time or are part of international efforts to establish daily provision of dust forecasts based on multi-model ensembles. The various models are introduced and described along with an overview on the importance of dust prediction activities and a historical perspective. Assimilation and evaluation aspects in dust prediction are also discussed.

  1. The Backpack Design Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  2. Smart textiles: Challenges and opportunities

    Science.gov (United States)

    Cherenack, Kunigunde; van Pieterson, Liesbeth

    2012-11-01

    Smart textiles research represents a new model for generating creative and novel solutions for integrating electronics into unusual environments and will result in new discoveries that push the boundaries of science forward. A key driver for smart textiles research is the fact that both textile and electronics fabrication processes are capable of functionalizing large-area surfaces at very high speeds. In this article we review the history of smart textiles development, introducing the main trends and technological challenges faced in this field. Then, we identify key challenges that are the focus of ongoing research. We then proceed to discuss fundamentals of smart textiles: textile fabrication methods and textile interconnect lines, textile sensor, and output device components and integration of commercial components into textile architectures. Next we discuss representative smart textile systems and finally provide our outlook over the field and a prediction for the future.

  3. Energy transition - economic challenge, climate challenge, industrial challenge

    International Nuclear Information System (INIS)

    This document highlights and discusses the different economic, climate and industrial challenges, identifies and discusses the different objectives and main results for a successful energy transition respectively in its relationships with the energy mix (the result is to divide emissions by a factor 4), with governance (the result should be a balanced distribution of energy governance), with energy consumption

  4. 全人源抗人肿瘤坏死因子相关诱导凋亡配体受体单克隆抗体蛋白高效表达体系的建立及其功能性分析%Establishment of a high efficient expression system of a novol human monoclonal antibody against tumour necrosis factor-related apoptosis-inducing ligand receptor and its functional characteristics

    Institute of Scientific and Technical Information of China (English)

    石佳宁; 韩晓健; 吕福莲; 毕冬梅; 金艾顺

    2015-01-01

    Objective To establishe a high efficient expression system and to generate mAb to tumour necrosis factor (TNF)-related apoptosis-inducing ligand receptor-1 (TRAIL)-R1,and to evaluate its functional characteristics.Methods We constructed a pcDNA3.4 vector containing anti-TRAIL-R1 Ab gene,and established a high efficient method expressing Ab protein using Expi293FTM cell expression system.We then purified TR1-404 Ab using Protein A/G.We detected the production of TR1-404 and its specific binding activity by the double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA.TRAIL-R1 expression on Hela cells and HCT116 cells was determined by flow cytometric assay.The survival and proliferation of Hela cells and HCT116 cells were analyzed after treatment with TR1-404 alone or TRAIL alone or combination of TR1-404 with TRAIL using MTT assay.We measured TR1-404 or TRAIL-induced tumor cell apoptosis using Annexin V/PI double staining.Results We successfully constructed plasmid expressing mAb to TRAIL-R1 and established a high efficient protein expression system.TR1-404 can bind to not only recombinant human TRAIL-R1 specifically but also TRAIL-R1 on surface of Hela and HCT116 cells.We found that TR1-404 enhanced TRAIL-induced cell apoptosis in Hela cells but not in HCT116.Conclusions In the study,we successfully establish a high protein expression system.TR1-404 can bind to TRAIL-R1 specifically.TR1-404 Ab increased TRAIL-mediated apoptosis in Hela tumor cells.%目的 建立高效表达全人源抗人肿瘤坏死因子相关诱导凋亡配体受体(TRAIL)-R1单克隆抗体(TR1-404)蛋白体系,并评价TR 1-404抗体蛋白功能特性.方法 构建pcDNA3.4载体抗体质粒,转染Expi293 FTM细胞,表达抗体蛋白.收集细胞培养上清,使用ProteinA/G纯化抗体蛋白.利用双抗体夹心和间接酶联免疫吸附试验(ELISA)检测抗体蛋白浓度及特异性.流式细胞分析检测TR1-404与Hela细胞和HCT116细胞表面TRAIL-R1的

  5. Using DFT methodology for more reliable predictive models: Design of inhibitors of Golgi α-Mannosidase II.

    Science.gov (United States)

    Bobovská, Adela; Tvaroška, Igor; Kóňa, Juraj

    2016-05-01

    Human Golgi α-mannosidase II (GMII), a zinc ion co-factor dependent glycoside hydrolase (E.C.3.2.1.114), is a pharmaceutical target for the design of inhibitors with anti-cancer activity. The discovery of an effective inhibitor is complicated by the fact that all known potent inhibitors of GMII are involved in unwanted co-inhibition with lysosomal α-mannosidase (LMan, E.C.3.2.1.24), a relative to GMII. Routine empirical QSAR models for both GMII and LMan did not work with a required accuracy. Therefore, we have developed a fast computational protocol to build predictive models combining interaction energy descriptors from an empirical docking scoring function (Glide-Schrödinger), Linear Interaction Energy (LIE) method, and quantum mechanical density functional theory (QM-DFT) calculations. The QSAR models were built and validated with a library of structurally diverse GMII and LMan inhibitors and non-active compounds. A critical role of QM-DFT descriptors for the more accurate prediction abilities of the models is demonstrated. The predictive ability of the models was significantly improved when going from the empirical docking scoring function to mixed empirical-QM-DFT QSAR models (Q(2)=0.78-0.86 when cross-validation procedures were carried out; and R(2)=0.81-0.83 for a testing set). The average error for the predicted ΔGbind decreased to 0.8-1.1kcalmol(-1). Also, 76-80% of non-active compounds were successfully filtered out from GMII and LMan inhibitors. The QSAR models with the fragmented QM-DFT descriptors may find a useful application in structure-based drug design where pure empirical and force field methods reached their limits and where quantum mechanics effects are critical for ligand-receptor interactions. The optimized models will apply in lead optimization processes for GMII drug developments. PMID:27035259

  6. Aeroacoustic Prediction and Noise Reduction

    OpenAIRE

    Delfs, Jan Werner

    2011-01-01

    An overview is given about aeroacoustic prediction and noise reduction technology from the field of aircraft noise. The simulation philosophy of the prediction methods is related to real world application, i.e. high Reynolds number flows, typical for aircraft. Noise reduction concepts are studied in two ways i) through a silent by design approach and b) by add-on treatments for existing aircraft components. Challenges are identified for future research.

  7. Towards predictive docking at aminergic G-protein coupled receptors

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; El-Fakahany, E. E.; Doležal, Vladimír

    2015-01-01

    Roč. 21, č. 11 (2015), s. 284. ISSN 1610-2940 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-05696S; GA ČR(CZ) GA305/09/0681 Institutional support: RVO:67985823 Keywords : induced-fit docking * pose scoring * molecular dynamics * ligand-receptor interaction Subject RIV: FH - Neurology Impact factor: 1.736, year: 2014

  8. The GREAT3 Challenge

    OpenAIRE

    Miyatake, Hironao; Mandelbaum, Rachel; collaboration, Barnaby Rowe on behalf of the GREAT3

    2014-01-01

    The GRavitational lEnsing Accuracy Testing 3 (GREAT3) challenge is an image analysis competition that aims to test algorithms to measure weak gravitational lensing from astronomical images. The challenge started in October 2013 and ends 30 April 2014. The challenge focuses on testing the impact on weak lensing measurements of realistically complex galaxy morphologies, realistic point spread function, and combination of multiple different exposures. It includes simulated ground- and space-base...

  9. Challenges of Relativistic Astrophysics

    CERN Document Server

    Opher, Reuven

    2013-01-01

    I discuss some of the most outstanding challenges in relativistic astrophysics in the subjects of: compact objects (Black Holes and Neutron Stars); dark sector (Dark Matter and Dark Energy); plasma astrophysics (Origin of Jets, Cosmic Rays and Magnetic Fields) and the primordial universe (Physics at the beginning of the Universe). In these four subjects, I discuss twelve of the most important challenges. These challenges give us insight into new physics that can only be studied in the large scale Universe. The near future possibilities, in observations and theory, for addressing these challenges, are also discussed.

  10. Prediction Markets

    DEFF Research Database (Denmark)

    Horn, Christian Franz; Ivens, Bjørn Sven; Ohneberg, Michael;

    2014-01-01

    In recent years, Prediction Markets gained growing interest as a forecasting tool among researchers as well as practitioners, which resulted in an increasing number of publications. In order to track the latest development of research, comprising the extent and focus of research, this article...... provides a comprehensive review and classification of the literature related to the topic of Prediction Markets. Overall, 316 relevant articles, published in the timeframe from 2007 through 2013, were identified and assigned to a herein presented classification scheme, differentiating between descriptive...... works, articles of theoretical nature, application-oriented studies and articles dealing with the topic of law and policy. The analysis of the research results reveals that more than half of the literature pool deals with the application and actual function tests of Prediction Markets. The results are...

  11. MicroRNA Targets - How to predict?

    OpenAIRE

    Das, Nabajit

    2012-01-01

    A number of web tools are available for the prediction and identification of target microRNAs (miRNAs). The choice, availability, validity and selection of an optimal yet appropriate tool are a challenge for the design of high throughput assays with promising miRNA targets. The current trends and challenges for target microRNAs (miRNAs) prediction, identification and selection is described in this review.

  12. Science Challenge Day

    Science.gov (United States)

    Siegel, Deborah

    2013-01-01

    Science fairs can be good motivators, but as extracurricular activities, they leave some students behind. However, by staging a Science Challenge Day at school, educators can involve all students in doing everything from choosing activities to judging projects. This article presents a model for running a successful Science Challenge Day. The…

  13. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming breastfeeding challenges Dealing with ... it into your life My breastfeeding story Partner resources Subscribe ... at the U.S. Department of Health and Human Services 200 Independence Avenue, S.W. • Washington, DC 20201 ...

  14. First Aid Challenge

    Science.gov (United States)

    Roman, Harry T.

    2011-01-01

    This article describes a challenge wherein students will be asked to design a portable first aid kit that is normally carried in a recreational vehicle (RV), but can also be hand-carried or backpacked off road for distances of approximately 1-2 miles. This can be a very practical challenge for the students because it touches everyone. Everybody…

  15. Prediction of molecular crystal structures

    CERN Document Server

    Beyer, T

    2001-01-01

    The ab initio prediction of molecular crystal structures is a scientific challenge. Reliability of first-principle prediction calculations would show a fundamental understanding of crystallisation. Crystal structure prediction is also of considerable practical importance as different crystalline arrangements of the same molecule in the solid state (polymorphs)are likely to have different physical properties. A method of crystal structure prediction based on lattice energy minimisation has been developed in this work. The choice of the intermolecular potential and of the molecular model is crucial for the results of such studies and both of these criteria have been investigated. An empirical atom-atom repulsion-dispersion potential for carboxylic acids has been derived and applied in a crystal structure prediction study of formic, benzoic and the polymorphic system of tetrolic acid. As many experimental crystal structure determinations at different temperatures are available for the polymorphic system of parac...

  16. Ligand-receptor binding kinetics in surface plasmon resonance cells: A Monte Carlo analysis

    CERN Document Server

    Carroll, Jacob; Forsten-Williams, Kimberly; Täuber, Uwe C

    2016-01-01

    Surface plasmon resonance (SPR) chips are widely used to measure association and dissociation rates for the binding kinetics between two species of chemicals, e.g., cell receptors and ligands. It is commonly assumed that ligands are spatially well mixed in the SPR region, and hence a mean-field rate equation description is appropriate. This approximation however ignores the spatial fluctuations as well as temporal correlations induced by multiple local rebinding events, which become prominent for slow diffusion rates and high binding affinities. We report detailed Monte Carlo simulations of ligand binding kinetics in an SPR cell subject to laminar flow. We extract the binding and dissociation rates by means of the techniques frequently employed in experimental analysis that are motivated by the mean-field approximation. We find major discrepancies in a wide parameter regime between the thus extracted rates and the known input simulation values. These results underscore the crucial quantitative importance of s...

  17. flp-32 Ligand/receptor silencing phenocopy faster plant pathogenic nematodes.

    Directory of Open Access Journals (Sweden)

    Louise E Atkinson

    2013-02-01

    Full Text Available Restrictions on nematicide usage underscore the need for novel control strategies for plant pathogenic nematodes such as Globodera pallida (potato cyst nematode that impose a significant economic burden on plant cultivation activities. The nematode neuropeptide signalling system is an attractive resource for novel control targets as it plays a critical role in sensory and motor functions. The FMRFamide-like peptides (FLPs form the largest and most diverse family of neuropeptides in invertebrates, and are structurally conserved across nematode species, highlighting the utility of the FLPergic system as a broad-spectrum control target. flp-32 is expressed widely across nematode species. This study investigates the role of flp-32 in G. pallida and shows that: (i Gp-flp-32 encodes the peptide AMRNALVRFamide; (ii Gp-flp-32 is expressed in the brain and ventral nerve cord of G. pallida; (iii migration rate increases in Gp-flp-32-silenced worms; (iv the ability of G. pallida to infect potato plant root systems is enhanced in Gp-flp-32-silenced worms; (v a novel putative Gp-flp-32 receptor (Gp-flp-32R is expressed in G. pallida; and, (vi Gp-flp-32R-silenced worms also display an increase in migration rate. This work demonstrates that Gp-flp-32 plays an intrinsic role in the modulation of locomotory behaviour in G. pallida and putatively interacts with at least one novel G-protein coupled receptor (Gp-flp-32R. This is the first functional characterisation of a parasitic nematode FLP-GPCR.

  18. Expression of tumor necrosis factor related apoptosis inducing ligand receptor in glioblastoma

    Institute of Scientific and Technical Information of China (English)

    Dongling Gao; Zhongwei Zhao; Hongxin Zhang; Lan Zhang; Kuisheng Chen; Yunhan Zhang

    2008-01-01

    BACKGROUND: Receptors for tumor necrosis factor related apoptosis inducing ligand (TRAIL) include death receptor 4, death receptor 5, decoy receptor 1, and decoy receptor 2. Activation of death receptor 4 and 5 selectively kills tumor cells.OBJECTIVE: To detect TRAIL receptor expression in glioblastoma by immunohistochemistry and RT-PCR and to compare this expression to that in normal brain tissue.DESIGN: Observational analysis.SETTING: Department of Pathology, the First Affiliated Hospital of Zhengzhou University; Henan Tumor Pathology Key Laboratory.PARTICIPANTS: Twenty-five patients (17 males and 8 females) who received glioblastoma resection were selected from the Fifth Affiliated Hospital of Zhengzhou University, between September 2003 to June 2004. All glioblastoma samples were diagnosed pathologically. Twenty patients (12 males and 8 females) with craniocerebral injury who received normal brain tissue resection were selected in the same time period. There were no significant differences in sex and age between glioblastoma patients or between craniocerebral injury patients (P>0.05). All patients and appropriate relatives provided informed consent, and this study was approved by the local research ethics committee.METHODS: Polyclonal antibody against TRAIL receptors and an immunohistochemical kit (batch number: 200502) were purchased from Boster Company, Wuhan. Immunohistochemistry: Expression of death receptor 4, death receptor 5, decoy receptor 1, and decoy receptor 2 were observed in both glioblastoma and normal brain tissue. The experiment was performed according to the kit instructions, and positive staining was brown-yellow. Assessment: There were no positive signals (-); weakly positive signals, positive cells75% (++++). Evaluation: Expression levels of TRAIL receptors were estimated in both normal brain tissue and glioblastoma. Expression of decoy receptor 1 and decoy receptor 2 mRNA in glioblastoma were detected by reverse transcription polymerase chain reaction, and expression of decoy receptor in glioblastoma was estimated.MAIN OUTCOME MEASURES: Comparison of death receptor and decoy receptor protein expression between glioblastoma and normal brain tissue; decoy receptor mRNA expression in glioblastoma.RESULTS: Death receptor protein expression was strongly positive (+++) in glioblastoma, while it was weakly positive (+,++) in normal brain tissue. Therefore, expression rate of death receptor protein in the glioblastoma was significantly higher than that in the normal brain tissue (x2=18.48,23.03, P<0.01). Decoy receptor protein expression in the glioblastoma was significantly lower than that in the normal brain tissue (x2=6.65,18.76, P<0.01). The level of decoy receptor mRNA expression in glioblastoma was significantly higher than those of protein expression (x2=9.82,10.09, P<0.01).CONCLUSION: High expression of death receptor and low expression of decoy receptor are frequently observed in glioblastoma, suggesting that TRAIL receptor genes show an anti-tumor and expressive response during the initiation and development of the tumor. There are significant differences in decoy receptor expression between normal brain tissue and glioblastoma, suggesting that the restricted expression of decoy receptor in glioblastoma is regulated at the post-transcriptional level.

  19. Analysis of ligand-receptor cross-linked fragments by mass spectrometry.

    Science.gov (United States)

    Son, C D; Sargsyan, H; Hurst, G B; Naider, F; Becker, J M

    2005-03-01

    G-protein coupled receptors (GPCRs) are a class of integral membrane receptor proteins that are characterized by a signature seven-transmembrane (7-TM) configuration. The alpha-factor receptor (Ste2p) from Saccharomyces cerevisiae is a GPCR that, upon binding of a peptide ligand, transduces a signal to initiate a cascade of events leading to the mating of haploid yeast cells. This study summarizes the application of affinity purification and of matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) experiments using biotinylated photoactivatable alpha-factor analogs. Affinity purification and enrichment of biotinylated peptides by monomeric avidin beads resulted in mass spectrometric detection of specific signals corresponding to cross-linked fragments of Ste2p. Data obtained from cyanogen bromide (CNBr) fragments of receptor cross-linked to an alpha-factor analog with the photoaffinity group p-benzoyl-l-phenylalanine on position 1 were in agreement with the previous results reported by our laboratory suggesting the cross-linking between position 1 of alpha-factor and a region of Ste2p covering residues 251-294. PMID:15787972

  20. The challenges of dismantling

    International Nuclear Information System (INIS)

    This document gathers Power Point presentations which address the contexts and challenges of dismantling (legal framework, safety and radiation protection challenges, waste processing industry), and propose illustrations of dismantling challenges (example of operations to prepare EURODIF dismantling and CLIGEET work-group on EURODIF dismantling, examples of dismantling of EDF installations and CLIs' opinion on the dismantling of EDF installations, Brennilis dismantling follow-up performed by the CLI, examples of dismantling of CEA installations and opinion of a CLI on the dismantling of CEA installations)

  1. Challenges of serious games

    Directory of Open Access Journals (Sweden)

    B. Fernández-Manjón

    2015-11-01

    Full Text Available Although educational games have revealed to be a very effective focus in diverse situations, their use in education is still very limited. In this paper we analyse the main challenges concerning educational games that, from our perspective, have to be approached so that the use of this kind of games can be widespread. These challenges are classified in three main dimensions: socio-cultural, educational and technological. Once the challenges are identified, some possible measures are suggested to address or reduce these problems so that the use of educational games may be widespread.

  2. Big Data Challenges

    Directory of Open Access Journals (Sweden)

    Alexandru Adrian TOLE

    2013-10-01

    Full Text Available The amount of data that is traveling across the internet today, not only that is large, but is complex as well. Companies, institutions, healthcare system etc., all of them use piles of data which are further used for creating reports in order to ensure continuity regarding the services that they have to offer. The process behind the results that these entities requests represents a challenge for software developers and companies that provide IT infrastructure. The challenge is how to manipulate an impressive volume of data that has to be securely delivered through the internet and reach its destination intact. This paper treats the challenges that Big Data creates.

  3. Challenging behaviour: a challenge to change.

    Science.gov (United States)

    van Berckelaer-Onnes, I A; van Loon, J; Peelen, A

    2002-09-01

    People with intellectual disability often exhibit severe behavioural problems. Treatment of these problems is frequently very difficult. In The Netherlands, parents, institutes, schools and others can request the services of an independent advisory team with a pool of professionals who have experience with individuals who exhibit challenging behaviour. In this article the methods of the team will be described using a 24-year-old man as an example. The process took almost 7 years. Finally, this man, who had been living full time in one room in total isolation from the rest of the world, fulfilled his heart's desire--visiting the UK by Hovercraft. PMID:12212917

  4. The challenges of risk society for impact assessment

    DEFF Research Database (Denmark)

    Larsen, Sanne Vammen

    2016-01-01

    , the challenge of delivering assessments and predictions and the challenge of handling differences of opinion and debate. Through a case example of integration of climate change in strategic environmental assessment, the paper uses empirical evidence from a survey and a series of interviews to carry...... debate is not clearly reflected....

  5. Community Challenge Grantees

    Data.gov (United States)

    Department of Housing and Urban Development — HUD's Community Challenge Grants aim to reform and reduce barriers to achieving affordable, economically vital and sustainable communities. The funds are awarded to...

  6. Brazil World Cup Challenges

    OpenAIRE

    MANSUR, R.

    2012-01-01

    Overcoming the productivity challenge is the main benefit of the 2014 World Cup for Brazilian people. The sustainable development of our cultural tourism industry will catapult the new middle class growing up rate.

  7. Better Buildings Challenge Overview

    Energy Technology Data Exchange (ETDEWEB)

    None

    2011-06-01

    The Better Buildings Challenge is a national leadership initiative calling on corporate chief executive officers, university presidents, and state and local leaders to make a significant commitment to building energy efficiency.

  8. Challenging Fieldwork Situations

    DEFF Research Database (Denmark)

    Bille, Thomas; Østergaard Steenfeldt, Vibeke

    2013-01-01

    understanding on the phenomenon of awkwardness as a natural way for researchers to respond to challenging fieldwork situations. Finally, they propose and unfold mutual interviewing and cooperative analysis as methods of investigating researcher’s subjectivity in facing such situations....

  9. The Electric Car Challenge.

    Science.gov (United States)

    Diehl, Brian E.

    1997-01-01

    Describes the Electric Car Challenge during which students applied methods of construction to build lightweight, strong vehicles that were powered by electricity. The activity required problem solving, sheet metal work, electricity, design, and construction skills. (JOW)

  10. A challenging read

    Directory of Open Access Journals (Sweden)

    Cathy Foley

    2004-11-01

    Full Text Available Andrei Mourachkine uses his new book to argue that superconductivity could be achieved at room temperature and, while his thesis may rest on some unconfirmed evidence, it does challenge preconceptions, says Cathy Foley.

  11. Brazil World Cup Challenges

    Directory of Open Access Journals (Sweden)

    MANSUR, R.

    2012-12-01

    Full Text Available Overcoming the productivity challenge is the main benefit of the 2014 World Cup for Brazilian people. The sustainable development of our cultural tourism industry will catapult the new middle class growing up rate.

  12. Challenges in marine instrumentation

    Digital Repository Service at National Institute of Oceanography (India)

    Afzulpurkar, S.; Desa, E.; Joseph, A.; Chakraborty, B.; Nayak, M.R.; Ranade, G.

    challenge for technology. Biosensors which can detect bioluminescence and other biological activities would play a major role. Autonomous instrumentation outfitted with different types of in-situ sensors would collect data without disturbing the system...

  13. Space Weather Prediction and Exascale Computing

    OpenAIRE

    Lapenta, Giovanni; Markidis, Stefano; Poedts, Stefaan; Vucinic, Dean

    2013-01-01

    Space weather can have a great effect on Earth's climate. Predicting the impact of space environment disturbances on Earth presents a challenge to scientists. Here, the ExaScience Lab's efforts are presented, which use exascale computing and new visualization tools to predict the arrival and impact of space events on Earth.

  14. Big Data Challenges

    OpenAIRE

    Alexandru Adrian TOLE

    2013-01-01

    The amount of data that is traveling across the internet today, not only that is large, but is complex as well. Companies, institutions, healthcare system etc., all of them use piles of data which are further used for creating reports in order to ensure continuity regarding the services that they have to offer. The process behind the results that these entities requests represents a challenge for software developers and companies that provide IT infrastructure. The challenge is how to manipul...

  15. Anthropocene Age Wicked Challenges

    DEFF Research Database (Denmark)

    Edgeman, Rick; Wu, Zhaohui

    2015-01-01

    weather events, drought, and desertification; threatened food supplies; water pollution, air pollution, and soil contamination; and the connection of these to disease, violence, and terrorism. Wicked challenges are discussed in relation to enterprise excellence, sustainability, resilience and robustness......Grand global challenges, including wicked human caused or influenced ones key to sustainability, characterize the Anthropocene Age. Among these are climate change driven by increased methane and CO2 in the atmosphere; consequent global warming and increasing intensity and incidence of extreme...

  16. Challenges in obesity research

    OpenAIRE

    Andreu Palou; Luisa Bonet, M.

    2013-01-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regard...

  17. Overcoming Safeguards Challenges

    International Nuclear Information System (INIS)

    The focus of the 2010 IAEA International Safeguards Symposium was how best, from a technical perspective, to prepare for future verification challenges during this time of change. By bringing together the leading experts in the field from across the world, this symposium provided an opportunity for stakeholders to explore possible solutions in support of the IAEA's nuclear verification mission, and to identify areas where the different stakeholders in the safeguards business can help address these challenges

  18. Optimal challenges in tennis

    OpenAIRE

    Clarke, S. R.; Norman, J.M.

    2012-01-01

    The use of technology in sport to assist umpires has been gradually introduced into several sports. This has now been extended to allow players to call upon technology to arbitrate when they disagree with the umpire's decision. Both tennis and cricket now allow the players to challenge a doubtful decision, which is reversed if the evidence shows it to be incorrect. However, the number of challenges is limited, and players must balance any possible immediate gain with the loss of a future righ...

  19. Prediction in projection

    Science.gov (United States)

    Garland, Joshua; Bradley, Elizabeth

    2015-12-01

    Prediction models that capture and use the structure of state-space dynamics can be very effective. In practice, however, one rarely has access to full information about that structure, and accurate reconstruction of the dynamics from scalar time-series data—e.g., via delay-coordinate embedding—can be a real challenge. In this paper, we show that forecast models that employ incomplete reconstructions of the dynamics—i.e., models that are not necessarily true embeddings—can produce surprisingly accurate predictions of the state of a dynamical system. In particular, we demonstrate the effectiveness of a simple near-neighbor forecast technique that works with a two-dimensional time-delay reconstruction of both low- and high-dimensional dynamical systems. Even though correctness of the topology may not be guaranteed for incomplete reconstructions like this, the dynamical structure that they do capture allows for accurate predictions—in many cases, even more accurate than predictions generated using a traditional embedding. This could be very useful in the context of real-time forecasting, where the human effort required to produce a correct delay-coordinate embedding is prohibitive.

  20. Challenges in obesity research.

    Science.gov (United States)

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. PMID:24010755

  1. Challenges in obesity research

    Directory of Open Access Journals (Sweden)

    Andreu Palou

    2013-09-01

    Full Text Available Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  2. The challenge of sustainability

    International Nuclear Information System (INIS)

    This paper discusses sustainability in a world that has changed rapidly. The author suggests that ecological assumptions embedded in communism and capitalism are badly flawed, but the flaws were not apparent when there were fewer than a billion people on earth living at low technology levels. Sustaining the earth's vital signs is a challenge to our perception of time, and the numbers - population, environmental damage, oil consumption, waste disposal - are too large to comprehend easily. There is a global debate about what sustainability means. In fact the challenge of sustainability is 6 different challenges: overcoming the tendency to deny inconvenient realities; establishing accurate indicators of human and ecological health; questions about the kinds of technology necessary to make the transition to sustainability; education; the need for an emotional bond between man and nature; rebuilding the existing democratic institutions. 16 refs

  3. DeepTox: Toxicity Prediction using Deep Learning

    OpenAIRE

    Andreas eMayr; Günter eKlambauer; Thomas eUnterthiner; Sepp eHochreiter

    2016-01-01

    The Tox21 Data Challenge has been the largest effort of the scientific community to compare computational methods for toxicity prediction. This challenge comprised 12,000 environmental chemicals and drugs which were measured for 12 different toxic effects by specifically designed assays. We participated in this challenge to assess the performance of Deep Learning in computational toxicity prediction. Deep Learning has already revolutionized image processing, speech recognition, and language u...

  4. British Muslims: A Challenge

    OpenAIRE

    Abdel-Hady, Zakaryya Mohamed [زكريا محمد عبد الهادي

    2007-01-01

    The Muslim community in Britain today face multiple challenges covering a wide range of spectrum from the basic right to exists, fighting the increasing trends of Islamophobia, having equal opportunities, to participate in public life, fully integrate within the society and be a positive member of the community. The recent events of September 11th in the US, July 7th in UK and the more recent row over the ban of the headscarf in UK and other European countries have placed tremendous challenge...

  5. Banff Challenge 2

    CERN Document Server

    Junk, Thomas R

    2011-01-01

    Experimental particle physics collaborations constantly seek newer and better ideas for improving the sensitivity of their searches for new particles and phenomena. Statistical techniques are the last step in interpreting the results of an experiment; they are used to make discoveries (hypothesis testing), and to measure parameters (point estimation). They are also used in the first step - experiment and analysis design. Banff Challenge 2 asks participants to test their methods of disco vering hidden signals in simulated datasets and of measuring the properties of these signals. The Challenge problems are described, and the performances of the submitted entries is summarized, for datasets with and without simulated signals present.

  6. Challenges facing production grids

    Energy Technology Data Exchange (ETDEWEB)

    Pordes, Ruth; /Fermilab

    2007-06-01

    Today's global communities of users expect quality of service from distributed Grid systems equivalent to that their local data centers. This must be coupled to ubiquitous access to the ensemble of processing and storage resources across multiple Grid infrastructures. We are still facing significant challenges in meeting these expectations, especially in the underlying security, a sustainable and successful economic model, and smoothing the boundaries between administrative and technical domains. Using the Open Science Grid as an example, I examine the status and challenges of Grids operating in production today.

  7. The challenge of conceiving

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Jørgensen, Ulrik

    2011-01-01

    One of the big challenges in the CDIO approach to engineering education is the first part focusing on conceiving problems to be handled and eventually solved. Traditional engineering education has been dominated by its focus on technical disciplines emphasising their individual tool box of problem...... problem from the perspective of engineering design challenges where the need for problem identification is obvious to avoid the pitfall to reproduce and piecemeal engineer already existing product or service concepts. Problem identification is not a simple desk research task as it often involves a...

  8. Grand Challenges in Music Information Research

    OpenAIRE

    Goto, Masataka

    2012-01-01

    This paper discusses some grand challenges in which music information research will impact our daily lives and our society in the future. Here, some fundamental questions are how to provide the best music for each person, how to predict music trends, how to enrich human-music relationships, how to evolve new music, and how to address environmental, energy issues by using music technologies. Our goal is to increase both attractiveness and social impacts of music information research in the fut...

  9. Challenges in Modeling Regional Climate Change (Invited)

    Science.gov (United States)

    Leung, L.

    2013-12-01

    Precipitation, soil moisture, and runoff are vital to ecosystems and human activities. Predicting changes in the space-time characteristics of these water cycle processes has been a longstanding challenge in climate modeling. Different modeling approaches have been developed to allow high resolution to be achieved using available computing resources. Although high resolution is necessary to better resolve regional forcing and processes, improvements in simulating water cycle response are difficult to demonstrate and climate models have so far shown irreducible sensitivity to model resolution, dynamical framework, and physics parameterizations that confounds reliable predictions of regional climate change. Additionally, regional climate responds to both regional and global forcing but predicting changes in regional and global forcing such as related to land use/land cover and aerosol requires improved understanding and modeling of the dynamics of human-earth system interactions. Furthermore, regional response and regional forcing may be related through complex interactions that are dependent on the regional climate regimes, making decisions on regional mitigation and adaptation more challenging. Examples of the aforementioned challenges from on-going research and possible future directions will be discussed.

  10. Programmed Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society.

    Science.gov (United States)

    Sholl, Lynette M; Aisner, Dara L; Allen, Timothy Craig; Beasley, Mary Beth; Borczuk, Alain C; Cagle, Philip T; Capelozzi, Vera; Dacic, Sanja; Hariri, Lida; Kerr, Keith M; Lantuejoul, Sylvie; Mino-Kenudson, Mari; Raparia, Kirtee; Rekhtman, Natasha; Roy-Chowdhuri, Sinchita; Thunnissen, Eric; Tsao, Ming Sound; Yatabe, Yasushi

    2016-04-01

    The binding of programmed death ligand-1 and ligand-2 (PD-L1 and PD-L2) to PD-1 blocks T-cell-mediated immune response to tumor. Antibodies that target programmed death receptor-1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non-small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non-small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay-one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for

  11. 76 FR 56819 - Centennial Challenges 2012 Sample Return Robot Challenge

    Science.gov (United States)

    2011-09-14

    ... SPACE ADMINISTRATION Centennial Challenges 2012 Sample Return Robot Challenge AGENCY: National... 42 U.S.C. 2451(314)(d). The 2012 Sample Return Robot Challenge is scheduled and teams that wish to... technologies of interest and value to NASA and the nation. The 2012 Sample Return Robot Challenge is a...

  12. 77 FR 70835 - Centennial Challenges 2013 Sample Return Robot Challenge

    Science.gov (United States)

    2012-11-27

    ... SPACE ADMINISTRATION Centennial Challenges 2013 Sample Return Robot Challenge AGENCY: National... in accordance with 51 U.S.C. 20144(c). The 2013 Sample Return Robot Challenge is scheduled and teams... Robot Challenge is a prize competition designed to encourage development of new technologies...

  13. Asia's new challenges

    DEFF Research Database (Denmark)

    Brach, Juliana; Vang, Jan

    2012-01-01

    Asian countries are currently undergoing significant changes with respect to their role in and interaction with the international economy. Despite their heterogeneity, Asian countries share the common aim to upgrade capacities, skills and capabilities. This paper aims at unpacking the challenges...

  14. The challenge of implementation

    DEFF Research Database (Denmark)

    Andersen, Karen Heide Hauge

    2015-01-01

    concepts in daily teaching, as it is strongly encouraged by policy makers and educations. This paper aims to discuss how lecturers experience the challenge of teaching their own discipline while being imposed to embrace and promote innovation and entrepreneurship teaching. Through a single study case of...

  15. Tackling the Unemployment Challenge

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    As the world's largest economy in transition, Chinafaces a severe unemployment challenge. With aworking population of 751 million, China'sunemployment rate stands at more than l O% in urbanareas," including rural surplus laborers, it is astaggering 20%. Since assuming office in March

  16. The blind hens’ challenge

    DEFF Research Database (Denmark)

    Sandøe, Peter; Hocking, Paul M.; Forkman, Björn;

    2014-01-01

    repellent, yet 'welfare-only' positions appear to be committed to endorsing this possibility if it produces welfare gains. We call this the 'Blind Hens' Challenge'. In this paper, we argue that there are both empirical and theoretical reasons why even those adopting 'welfare-only' views should be concerned...

  17. MALL: The Pedagogical Challenges

    Science.gov (United States)

    Burston, Jack

    2014-01-01

    In this paper the development of mobile-assisted language learning (MALL) over the past 20 years is reviewed with a particular focus on the pedagogical challenges facing its exploitation. Following a consideration of the definition of mobile learning, the paper describes the dominant mobile technologies upon which MALL applications have been…

  18. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... and Human Services Office on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us Contact Us Text size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming ...

  19. Electric Vehicle Battery Challenge

    Science.gov (United States)

    Roman, Harry T.

    2014-01-01

    A serious drawback to electric vehicles [batteries only] is the idle time needed to recharge their batteries. In this challenge, students can develop ideas and concepts for battery change-out at automotive service stations. Such a capability would extend the range of electric vehicles.

  20. A Challenge to Watson

    Science.gov (United States)

    Detterman, Douglas K.

    2011-01-01

    Watson's Jeopardy victory raises the question of the similarity of artificial intelligence and human intelligence. Those of us who study human intelligence issue a challenge to the artificial intelligence community. We will construct a unique battery of tests for any computer that would provide an actual IQ score for the computer. This is the same…

  1. The Moon Challenge

    Science.gov (United States)

    Fitzsimmons, Pat; Leddy, Diana; Johnson, Lindy; Biggam, Sue; Locke, Suzan

    2013-01-01

    This article describes a first-grade research project that incorporates trade books and challenges misconceptions. Educators see the power of their students' wonder at work in their classrooms on a daily basis. This wonder must be nourished by students' own experiences--observing the moon on a crystal clear night--as well as by having…

  2. Ecommerce: Ongoing Challenges

    Directory of Open Access Journals (Sweden)

    Derek Mohammed

    2010-08-01

    Full Text Available This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  3. Challenging the Boundaries

    DEFF Research Database (Denmark)

    Nørgaard, Nina

    2004-01-01

    To many people, challenging the boundaries between the traditional disciplines in foreign language studies means doing cultural studies. The aim of this article is to pull in a different direction by suggesting how the interface between linguistics and literature may be another fertile field to e...

  4. Challenging and valuable

    OpenAIRE

    Van Hal, J.D.M.

    2008-01-01

    Challenging and valuable Inaugural speech given on May 7th 2008 at the occasion of the acceptance of the position of Professor Sustainable Housing Transformation at the faculty of Architeeture of the Delft University of Technology by Prof. J.D.M. van Hal MSc PhD.

  5. Hopes and Challenges

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China tops the medal tally again at the Asian Games but still faces challenges in some events The curtain of the 16th Asian Games has fallen, but the 15 days of exciting competitions will be recorded in the history of the Games.

  6. Ecommerce: Ongoing Challenges

    OpenAIRE

    Derek Mohammed

    2010-01-01

    This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  7. The diesel challenge

    International Nuclear Information System (INIS)

    This article is focused on the challenges being faced by the diesel producer and these include a number of interesting developments which illustrate the highly competitive world of the European refiner. These include: The tightening quality requirements being legislated coupled with the availability of the ''city diesel'' from Scandinavia and elsewhere which is already being sold into the market. For a time there will be a clear means of product differentiation. One of the key questions is whether the consumer will value the quality difference; a growing demand for diesel which is outstripping the growth in gasoline demand and causing refiners headaches when it comes to balancing their supply/demand barrels; the emergence of alternative fuels which are challenging the traditional markets of the refiner and in particular, the niche markets for the higher quality diesel fuels. All of this at a time of poor margins and over-capacity in the industry with further major challenges ahead such as fuel oil disposal, tighter environmental standards and the likelihood of heavier, higher sulphur crude oils in the future. Clearly, in such a difficult and highly-competitive business environment it will be important to find low-cost solutions to the challenges of the diesel quality changes. An innovative approach will be required to identify the cheapest and best route to enable the manufacture of the new quality diesel. (Author)

  8. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Experience in many parts of the developing world has shown thatfood fortification offers a cost-effective and sustainable solution to the problem of micronutrient malnutrition. Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs, governments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy. On the other hand, formidable challenges still remain in many countries in Asia, constraining the widespread adoption of this strategy. The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making. The government faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort. Industry faces the challenge of adapting its production system to the requirements of fortification in order that they can contribute to social objectives while pursuing their economic objectives. The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification, as these players in turn face the challenges that confront them.

  9. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    RODOLFOF.FLORENTINO

    2001-01-01

    Experience in many parts of the developing world has shown that food fortification offers a costeffective and sustainable solution to the problem of micronutrient malnutrition.Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs,govenments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy.On the other hand,formidable challenges still remain in many countries in Asia,constraining the widespread adoption of this strategy,The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making,The governent faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort.Industry faces the challenge of adapting its production system to the requirements of fortification in oreder that they can contribute to social bojectives while pursuing their economic objectives,The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification,as these players in turn face the challenges that confront them.

  10. The Clay Challenge Continues...

    Science.gov (United States)

    Coy, Mary

    2007-01-01

    It was time for yet another challenge. Bright colored glazes were on hiatus; earth tones and mixed media took center stage. Inspiration was provided this time by the myriad Native American potters from the desert Southwest. The project: create a coil pot that demonstrates interesting form and good artistry and reflects, through symbolism or mixed…

  11. A Survey Paper on Crime Prediction Technique Using Data Mining

    OpenAIRE

    Nikhil Dubey; Setu Kumar Chaturvedi

    2014-01-01

    Crime prediction is an attempt to identify and reducing the future crime. Crime prediction uses past data and after analyzing data, predict the future crime with location and time. In present days serial criminal cases rapidly occur so it is an challenging task to predict future crime accurately with better performance. Data mining technique are very useful to solving Crime detection problem. So the aim of this paper to study various computational techniques used to predict fu...

  12. Evaluating the Predictive Validity of the Computerized Comprehension Task: Comprehension Predicts Production

    Science.gov (United States)

    Friend, Margaret; Schmitt, Sara A.; Simpson, Adrianne M.

    2012-01-01

    Until recently, the challenges inherent in measuring comprehension have impeded our ability to predict the course of language acquisition. The present research reports on a longitudinal assessment of the convergent and predictive validity of the MacArthur-Bates Communicative Development Inventories: Words and Gestures (CDI: WG; Fenson et al.,…

  13. Energy Predictions 2011

    International Nuclear Information System (INIS)

    Even as the recession begins to subside, the energy sector is still likely to experience challenging conditions as we enter 2011. It should be remembered how very important a role energy plays in driving the global economy. Serving as a simple yet global and unified measure of economic recovery, it is oil's price range and the strength and sustainability of the recovery which will impact the ways in which all forms of energy are produced and consumed. The report aims for a closer insight into these predictions: What will happen with M and A (Mergers and Acquisitions) in the energy industry?; What are the prospects for renewables?; Will the water-energy nexus grow in importance?; How will technological leaps and bounds affect E and P (exploration and production) operations?; What about electric cars? This is the second year Deloitte's Global Energy and Resources Group has published its predictions for the year ahead. The report is based on in-depth interviews with clients, industry analysts, and senior energy practitioners from Deloitte member firms around the world.

  14. Challenges in Request Management

    DEFF Research Database (Denmark)

    Sommer, Anita Friis

    2014-01-01

    profitability. This research study seeks to investigate the challenges of RQM in practice. Existing demand chain management literature is used as a basis for developing a RQM framework. RQM is investigated through an explorative research design in a dyadic B2B case study including a global industrial company......Request management (RQM) is a new term used for managing customer requests for new products. It is the counterpart to typical product development processes, which has no direct customer involvement. It is essential to manage customer requests in a structured and efficient way to obtain...... and its customers. The study provides an insight into a new area of supply chain management, including the process activity flow and challenges involved across the process. Furthermore, the method is dyadic including the customer in the case study, which is rare in related research....

  15. Supernova Photometric Classification Challenge

    CERN Document Server

    Kessler, Richard; Jha, Saurabh; Kuhlmann, Stephen

    2010-01-01

    We have publicly released a blinded mix of simulated SNe, with types (Ia, Ib, Ic, II) selected in proportion to their expected rate. The simulation is realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). We challenge scientists to run their classification algorithms and report a type for each SN. A spectroscopically confirmed subset is provided for training. The goals of this challenge are to (1) learn the relative strengths and weaknesses of the different classification algorithms, (2) use the results to improve classification algorithms, and (3) understand what spectroscopically confirmed sub-...

  16. Mathematical olympiad challenges

    CERN Document Server

    Andreescu, Titu

    2000-01-01

    Mathematical Olympiad Challenges is a rich collection of problems put together by two experienced and well-known professors and coaches of the U.S. International Mathematical Olympiad Team. Hundreds of beautiful, challenging, and instructive problems from algebra, geometry, trigonometry, combinatorics, and number theory were selected from numerous mathematical competitions and journals. An important feature of the work is the comprehensive background material provided with each grouping of problems. The problems are clustered by topic into self-contained sections with solutions provided separately. All sections start with an essay discussing basic facts and one or two representative examples. A list of carefully chosen problems follows and the reader is invited to take them on. Additionally, historical insights and asides are presented to stimulate further inquiry. The emphasis throughout is on encouraging readers to move away from routine exercises and memorized algorithms toward creative solutions to open-e...

  17. Challenges in radioecology

    International Nuclear Information System (INIS)

    Today, radioecology covers a broad scientific field; from the source to long term environmental impact from ionizing radiation. To summarize key challenges within radioecology, the present paper focuses upon knowledge gaps related to processes, mechanisms and variables contributing most to the overall uncertainties in environmental impact assessments. A series of sources related to the nuclear weapon cycle and the civil nuclear cycle has contributed, is still contributing or can potentially contribute to release of radionuclides to the environment in the future. The speciation of most radionuclides depends on the source and release conditions, and will influence ecosystem transport, biological uptake, doses and effects in flora and fauna. Radionuclides may also co-occur in contaminant mixtures (e.g., metals, organics), which potentially could lead to synergisms or antagonisms. Thus, challenges associated with the links between the source or release term - radionuclide speciation - ecosystem transfer - exposure - response relationships are highlighted.

  18. Challenges in sexual medicine

    DEFF Research Database (Denmark)

    Cellek, Selim; Giraldi, Annamaria

    2012-01-01

    The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have...... placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain...... several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field...

  19. Challenges to Resistance Welding

    DEFF Research Database (Denmark)

    Song, Quanfeng

    This report originates from the compulsory defense during my Ph.D. study at the Technical University of Denmark. Resistance welding is an old and well-proven technology. Yet the emergence of more and more new materials, new designs, invention off new joining techniques, and more stringent...... requirement in quality have imposed challenges to the resistance welding. More some research and development have to be done to adapt the old technology to the manufacturing industry of the 21st century. In the 1st part of the report, the challenging factors to the resistance welding are reviewed. Numerical...... simulation of resistance welding has been under development for many years. Yet it is no easy to make simulation results reliable and accurate because of the complexity of resistance welding process. In the 2nd part of the report numerical modeling of resistance welding is reviewed, some critical factors to...

  20. RNA structure prediction: progress and perspective

    CERN Document Server

    Shi, Ya-Zhou; Wang, Feng-Hua; Tan, Zhi-Jie

    2014-01-01

    Many recent exciting discoveries have revealed the versatility of RNAs and their importance in a variety of cellular functions which are strongly coupled to RNA structures. To understand the functions of RNAs, some structure prediction models have been developed in recent years. In this review, the progress in computational models for RNA structure prediction is introduced and the distinguishing features of many outstanding algorithms are discussed, emphasizing three dimensional (3D) structure prediction. A promising coarse-grained model for predicting RNA 3D structure, stability and salt effect is also introduced briefly. Finally, we discuss the major challenges in the RNA 3D structure modeling.

  1. Terabit Wireless Communication Challenges

    Science.gov (United States)

    Hwu, Shian U.

    2012-01-01

    This presentation briefly discusses a research effort on Terabit Wireless communication systems for possible space applications. Recently, terahertz (THz) technology (300-3000 GHz frequency) has attracted a great deal of interest from academia and industry. This is due to a number of interesting features of THz waves, including the nearly unlimited bandwidths available, and the non-ionizing radiation nature which does not damage human tissues and DNA with minimum health threat. Also, as millimeter-wave communication systems mature, the focus of research is, naturally, moving to the THz range. Many scientists regard THz as the last great frontier of the electromagnetic spectrum, but finding new applications outside the traditional niches of radio astronomy, Earth and planetary remote sensing, and molecular spectroscopy particularly in biomedical imaging and wireless communications has been relatively slow. Radiologists find this area of study so attractive because t-rays are non-ionizing, which suggests no harm is done to tissue or DNA. They also offer the possibility of performing spectroscopic measurements over a very wide frequency range, and can even capture signatures from liquids and solids. According to Shannon theory, the broad bandwidth of the THz frequency bands can be used for terabit-per-second (Tb/s) wireless communication systems. This enables several new applications, such as cell phones with 360 degrees autostereoscopic displays, optic-fiber replacement, and wireless Tb/s file transferring. Although THz technology could satisfy the demand for an extremely high data rate, a number of technical challenges need to be overcome before its development. This presentation provides an overview the state-of-the- art in THz wireless communication and the technical challenges for an emerging application in Terabit wireless systems. The main issue for THz wave propagation is the high atmospheric attenuation, which is dominated by water vapor absorption in the THz

  2. Energy challenges in Asia

    International Nuclear Information System (INIS)

    Energy challenges represent one of the most important security paradigms in the Asia Pacific region where you have a mixture of growing energy dependency, fuelled by high economic growth, the emergence of new major players like China and India, and a quasi-complete absence of regional regulatory mechanisms to tackle the challenges in a multilateral way. These challenges mostly concern Japan and China, where crucial energy issues are aggravated by power rivalry, historical and ideological issues, and a lack of both economic and political harmony between them. Neither countries are self sufficient in terms of energy needs. This can lead to a shared analysis and common approaches regarding Japan and China concerning this issue. Their cases are. however very different and the solutions applied are related to different world views that are not easily reconcilable. Both countries share common objectives: both want security and stable supply. But there are also big divergences and these divergences could be new sources of conflict and misunderstanding between Tokyo and Beijing. One of the main differences is history related. Both China and Japan are uneasy regarding outside energy dependency. In Japan, memories of the pre-war oil embargo have not disappeared. The oil shocks of the 70's renewed this uneasiness. However, Japan's outside dependency is not new. Tokyo has learned to live with it, finding a system to alleviate this vulnerability in cooperation with its partners, multilateral institutions like the International Energy Agency (IEA). China's outside dependency is new. The country's dependency on oil, which began in 1993, is particularly challenging since the principles of independence, non interference and military autonomy, principles at the core of Maoist foreign strategy, did not completely disappear in spite of China's new policy of reform and opening up. China's leadership, even the fourth generation, did not forget its isolation during the 60's and 70's

  3. Librarianship: A Challenging Profession

    OpenAIRE

    Lalithabai, K K.

    1996-01-01

    Defines librarianship as the art and science of managing recorded knowledge. Observes that in earlier days when the recorded sources of information were limited in number, scholars could be the users as well as managers of libraries. But today’s libraries with torrents of information sources and users on either side makes management a truly challenging task requiring highly specialized knowledge and training in the sophisticated techniques of information handling. Views that in information co...

  4. Challenges in Danish VET

    DEFF Research Database (Denmark)

    Aarkrog, Vibe

    2011-01-01

    In Denmark the 95 percent target, meaning that in 2015 95 percent of a youth cohort should complete a youth education programme, is particularly challenging for the vocational educational and training (VET) system. In the article is given a short outline of the significant characteristics of the...... Danish dual VET system as well as of the current central initiatives aimed at reaching the 95 percent target....

  5. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    OpenAIRE

    Varma, S. K.; RAPELLIWAR A; S. Sutradhar; THAWARE P; Misra, A. K.

    2013-01-01

    Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Impro...

  6. CHALLENGES FOR FOREIGN TEACHERS

    Institute of Scientific and Technical Information of China (English)

    DengJing

    2004-01-01

    The learner differences and contrasts between the two cultures involved are important aspects that influence foreign language teaching and learning. The foreign teacher as an outsider of the learner's native culture, inevitably faces quite a few challenges. With the focus on the self-esteem, character types, and motivation of the learner, the paper analyses how these factors influence the foreign teacher's teaching. Relevant solutions are also proposed.

  7. Challenges in Crowd Simulation

    OpenAIRE

    Thalmann, Daniel; Grillon, Helena; Maim, Jonathan; Yersin, Barbara

    2009-01-01

    The purpose of this paper is to identify the problems to solve in order to simulate real-time crowds in a Virtual Environment. We try to classify these problems and study how they have been addressed until now by the research community and our Lab in particular. We then discuss for each problem what are the,future challenges and how to address them.

  8. The First Provenance Challenge

    OpenAIRE

    Moreau, Luc; Ludaescher, Bertram; Altintas, Ilkay; Barga, Roger S.; Bowers, Shawn; Callahan, Steven; Chin Jr., George; Clifford, Ben; Cohen, Shirley; Cohen-Boulakia, Sarah; Davidson, Susan; Deelman, Ewa; Digiampietri, Luciano; Foster, Ian; Freire, Juliana

    2008-01-01

    The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the...

  9. South China Sea Challenge

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    China's attempts to solve disputes with ASEAN over the South China Sea help regional peace China's marine economy and security are currently faced with new challenges, requiring careful handling, especially in disputes with ASEAN countries and in promoting common development of the South China Sea. The outcome of how this is dealt with could undoubtedly pave the way for solutions to other oceanic disputes. The South China Sea is located south of

  10. Public budgets: New challenges

    OpenAIRE

    Attila, György

    2010-01-01

    Budgeting is passing through changes all over the world in order to find more efficient ways to guide public money usage. The last half of century gave us multiple examples of how to improve budgetary performance, but there are a lot to do in next decades to accomplish this goal. The challenges regarding public budgeting are: using accrual based budgeting, use performance information to determine the allocations for each agency, and strengthening the budgetary transparency.

  11. Sustainability challenges and trends

    OpenAIRE

    De Ridder, M.

    2011-01-01

    In the coming decades, increases in population, income and health will put additional pressures on our planet’s biosphere. To meet the needs of future generations, we need to adapt our ways of living and definitions of economic development. A transition to a more sustainable world is imperative if we want to stop depleting the Earth’s resources more quickly than it can regenerate them. This paper synthesizes current trends and challenges that are relevant for the policy debate on sustainabili...

  12. ATLAS Data Challenge 1

    CERN Document Server

    DC1 TaskForce

    2003-01-01

    The ATLAS Collaboration at CERN is preparing for the data taking and analysis at LHC that will start in 2007. Therefore, in 2002 a series of Data Challenges (DC's) was started whose goals are the validation of the Computing Model, of the complete software suite, of the data model, and to ensure the correctness of the technical choices to be made. A major feature of the first Data Challenge (DC1) was the preparation and the deployment of the software required for the production of large event samples for the High Level Trigger and Physics communities, and the production of those large data samples as a worldwide distributed activity. It should be noted that it was not an option to "run everything at CERN" even if we had wanted to; the resources were not available at CERN to carry out the production on a reasonable time-scale. We were therefore faced with the great challenge of organising and then carrying out this large-scale production at a significant number of sites around the world. However, the benefits o...

  13. IDEOLOGICALLY CHALLENGING ENTERTAINMENT (ICE

    Directory of Open Access Journals (Sweden)

    Dana Lori Chalmers

    2015-09-01

    Full Text Available Ideologically Challenging Entertainment (ICE is entertainment that challenges ‘us vs. them’ ideologies associated with radicalization, violent conflict and terrorism. ICE presents multiple perspectives on a conflict through mainstream entertainment. This article introduces the theoretical underpinnings of ICE, the first ICE production and the audience responses to it. The first ICE production was Two Merchants: The Merchant of Venice adapted to challenge ideologies of the Arab-Israeli Conflict. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views. Each performance included two versions of the adaptation: a Jewish dominated society with an Arab Muslim minority, contrasted with an Arab Muslim dominated society and a Jewish minority. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views to become more tolerant of differences away from ideological radicalization. Of audience members who did not initially agree with the premise of the production, 40% reconsidered their ideological views, indicating increased tolerance, greater awareness of and desire to change their own prejudices. In addition, 86% of the audience expressed their intention to discuss the production with others, thereby encouraging critical engagement with, and broader dissemination of the message. These outcomes suggest that high quality entertainment – as defined by audience responses to it - can become a powerful tool in the struggle against radicalised ideologies.

  14. JWST ISIM Distortion Analysis Challenge

    Science.gov (United States)

    Cifie, Emmanuel; Matzinger, Liz; Kuhn, Jonathan; Fan, Terry

    2004-01-01

    Very tight distortion requirements are imposed on the JWST's ISM structure due to the sensitivity of the telescope's mirror segment and science instrument positioning. The ISIM structure is a three dimensional truss with asymmetric gusseting and metal fittings. One of the primary challenges for ISIM's analysis team is predicting the thermal distortion of the structure both from the bulk cooldown from ambient to cryo, and the smaller temperature changes within the cryogenic operating environment. As a first cut to estimate thermal distortions, a finite element model of bar elements was created. Elements representing joint areas and metal fittings use effective properties that match the behavior of the stack-up of the composite tube, gusset and adhesive under mechanical and thermal loads. These properties were derived by matching tip deflections of a solid model simplified T-joint. Because of the structure s asymmetric gusseting, this effective property model is a first attempt at predicting rotations that cannot be captured with a smeared CTE approach. In addition to the finite element analysis, several first order calculations have been performed to gauge the feasibility of the material design. Because of the stringent thermal distortion requirements at cryogenic temperatures, a composite tube material with near zero or negative CTE is required. A preliminary hand analysis of the contribution of the various components along the distortion path between FGS and the other instruments, neglecting second order effects were examined. A plot of bounding tube longitudinal and transverse CTEs for thermal stability requirements was generated to help determine the feasibility of meeting these requirements. This analysis is a work in progress en route to a large degree of freedom hi-fidelity FEA model for distortion analysis. Methods of model reduction, such as superelements, are currently being investigated.

  15. Perishable Inventory Challenges

    DEFF Research Database (Denmark)

    Damgaard, Cecilie Maria; Nguyen, Vivi Thuy; Hvolby, Hans-Henrik;

    2012-01-01

    The paper investigates how inventory control of perishable items is managed and line up some possible options of improvement. This includes a review of relevant literature dealing with the challenges of determining ordering policies for perishable products and a study of how the current procedures...... in the retail supply chains. The goal is to find and evaluate the parameters which affect the decision making process, when finding the optimal order quantity and order time. The paper takes a starting point in the retail industry but links to other industries....

  16. Caspian sea: petroleum challenges

    International Nuclear Information System (INIS)

    The Caspian sea is one of the world areas the most promising in terms of investments and petroleum development. This study presents the petroleum challenges generated by this hydrocarbons reserve. The first part discusses the juridical status (sea or lake), the petroleum and the gas reserves, the ecosystem and the today environment (fishing and caviar), the geostrategic situation and the transport of gas and oil. It provides also a chronology from 1729 to 2005, a selection of Internet sites, books and reports on the subject and identity sheets of the countries around the Caspian sea. (A.L.B.)

  17. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  18. Energy challenges in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Niquet, V.

    2007-07-01

    Energy challenges represent one of the most important security paradigms in the Asia Pacific region where you have a mixture of growing energy dependency, fuelled by high economic growth, the emergence of new major players like China and India, and a quasi-complete absence of regional regulatory mechanisms to tackle the challenges in a multilateral way. These challenges mostly concern Japan and China, where crucial energy issues are aggravated by power rivalry, historical and ideological issues, and a lack of both economic and political harmony between them. Neither countries are self sufficient in terms of energy needs. This can lead to a shared analysis and common approaches regarding Japan and China concerning this issue. Their cases are. however very different and the solutions applied are related to different world views that are not easily reconcilable. Both countries share common objectives: both want security and stable supply. But there are also big divergences and these divergences could be new sources of conflict and misunderstanding between Tokyo and Beijing. One of the main differences is history related. Both China and Japan are uneasy regarding outside energy dependency. In Japan, memories of the pre-war oil embargo have not disappeared. The oil shocks of the 70's renewed this uneasiness. However, Japan's outside dependency is not new. Tokyo has learned to live with it, finding a system to alleviate this vulnerability in cooperation with its partners, multilateral institutions like the International Energy Agency (IEA). China's outside dependency is new. The country's dependency on oil, which began in 1993, is particularly challenging since the principles of independence, non interference and military autonomy, principles at the core of Maoist foreign strategy, did not completely disappear in spite of China's new policy of reform and opening up. China's leadership, even the fourth generation, did not forget its isolation

  19. Semantic Web Evaluation Challenge

    CERN Document Server

    2014-01-01

    This book constitutes the thoroughly refereed post conference proceedings of the first edition of the Semantic Web Evaluation Challenge, SemWebEval 2014, co-located with the 11th Extended Semantic Web conference, held in Anissaras, Crete, Greece, in May 2014. This book includes the descriptions of all methods and tools that competed at SemWebEval 2014, together with a detailed description of the tasks, evaluation procedures and datasets. The contributions are grouped in three areas: semantic publishing (sempub), concept-level sentiment analysis (ssa), and linked-data enabled recommender systems (recsys).

  20. New challenges? Well, certainly!

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    New challenges? Well, certainly! With the internationalization of European higher education, teaching and learning through the medium of a foreign language has become more and more widespread in recent years. This requires, of course, that lecturers as well as students have the necessary language...... proficiency, but research as well as experience on the ground tells us that this is not enough. Everyone must learn to navigate in the multilingual and multicultural learning space because lecturers as well as students may come from different countries and cultures and therefore have different first languages...

  1. The New Asian Challenge

    OpenAIRE

    C. Fred Bergsten

    2000-01-01

    The initial postwar challenge from East Asia was economic. Japan crashed back into global markets in the 1960s, became the largest surplus and creditor country in the 1980s, and was viewed by many as the world’s dominant economy by 1990. The newly industrialized countries (Korea, Taiwan, Hong Kong, Singapore) followed suit on a smaller but still substantial scale shortly thereafter. China only re-entered world commerce in the 1980s but has now become the second largest economy (in purchasing ...

  2. The challenge of managing fusariosis.

    Science.gov (United States)

    Muhammed, Maged; Coleman, Jeffrey J; Carneiro, Herman A; Mylonakis, Eleftherios

    2011-01-01

    Fusarium is the second most frequent mold involved in fungal infections and is particularly important among immunocompromised patients. Culture methods and microscopy are still routinely used in clinical laboratories to identify Fusarium spp, and more sophisticated, timely, and effective methods for detecting Fusarium spp. in laboratory samples could improve the outcome of the patient. These investigational diagnostic approaches include serological assays and specific nested PCR assays that can yield positive and negative predictive values of over 90%. Other assays in development, such as mass spectroscopy techniques, can provide accurate and consistent results. The treatment of fusariosis in immunocompromised patients remains a challenge and the prognosis of systemic fusariosis in this population remains poor. Successful treatment is highly dependent on the particular Fusarium species involved in the infection. High dose intravenous amphotericin B formulation is recommended as the first line of therapy in management of fusariosis in patients. Voriconazole is also effective in treating fusariosis. Intolerance, contraindication, or failure of the amphotericin B formulation warrants the use of voriconazole as an alternative agent, and posaconazole is licensed as salvage therapy against invasive fusariosis. Adjunctive therapies such as surgical debridement of infected tissue, granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) infusions, or granulocyte transfusions are also tools for managing fusariosis. In conclusion, Fusarium infection is considered an emerging problem and should be suspected in immunocompromised patients experiencing systemic infection and should be treated accordingly. PMID:21304267

  3. Silicon spintronics: Progress and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Sverdlov, Viktor; Selberherr, Siegfried, E-mail: Selberherr@TUWien.ac.at

    2015-07-14

    Electron spin attracts much attention as an alternative to the electron charge degree of freedom for low-power reprogrammable logic and non-volatile memory applications. Silicon appears to be the perfect material for spin-driven applications. Recent progress and challenges regarding spin-based devices are reviewed. An order of magnitude enhancement of the electron spin lifetime in silicon thin films by shear strain is predicted and its impact on spin transport in SpinFETs is discussed. A relatively weak coupling between spin and effective electric field in silicon allows magnetoresistance modulation at room temperature, however, for long channel lengths. Due to tunneling magnetoresistance and spin transfer torque effects, a much stronger coupling between the spin (magnetization) orientation and charge current is achieved in magnetic tunnel junctions. Magnetic random access memory (MRAM) built on magnetic tunnel junctions is CMOS compatible and possesses all properties needed for future universal memory. Designs of spin-based non-volatile MRAM cells are presented. By means of micromagnetic simulations it is demonstrated that a substantial reduction of the switching time can be achieved. Finally, it is shown that any two arbitrary memory cells from an MRAM array can be used to perform a logic operation. Thus, an intrinsic non-volatile logic-in-memory architecture can be realized.

  4. Silicon spintronics: Progress and challenges

    International Nuclear Information System (INIS)

    Electron spin attracts much attention as an alternative to the electron charge degree of freedom for low-power reprogrammable logic and non-volatile memory applications. Silicon appears to be the perfect material for spin-driven applications. Recent progress and challenges regarding spin-based devices are reviewed. An order of magnitude enhancement of the electron spin lifetime in silicon thin films by shear strain is predicted and its impact on spin transport in SpinFETs is discussed. A relatively weak coupling between spin and effective electric field in silicon allows magnetoresistance modulation at room temperature, however, for long channel lengths. Due to tunneling magnetoresistance and spin transfer torque effects, a much stronger coupling between the spin (magnetization) orientation and charge current is achieved in magnetic tunnel junctions. Magnetic random access memory (MRAM) built on magnetic tunnel junctions is CMOS compatible and possesses all properties needed for future universal memory. Designs of spin-based non-volatile MRAM cells are presented. By means of micromagnetic simulations it is demonstrated that a substantial reduction of the switching time can be achieved. Finally, it is shown that any two arbitrary memory cells from an MRAM array can be used to perform a logic operation. Thus, an intrinsic non-volatile logic-in-memory architecture can be realized

  5. Spintronics - achievements, prospects and challenges

    International Nuclear Information System (INIS)

    Spintronics utilizes not only the charge of the electrons but also their spin, or resulting magnetization, to realize functional devices of information technologies. In the last decade, spintronics has become a quickly developing research area for solid state scientists. Already, spintronics (or magnetoelectronics) has revolutionized the market for storage devices. Some predicted advantages of the new emerging technology are the nonvolatility of data storage, the increased speed of data processing, the high storage density, and the low energy consumption. To exploit the full potential of spintronics and facilitate design of novel functional devices, it is necessary to exploit the basic physics and progress materials research to find new materials satisfying particular demands. A general understanding of the structure property relationship is a necessary prerequisite for further development of spintronics. In these three lectures, the most important developments in the field of spintronics will be presented and related to the materials science. In particular, the problems connected to spin current such as, magnetoresistance, giant magnetoresistance (GMR), tunneling magnetorestance (TMR), and spin injection from ferromagnetic material will be discussed. In this context, new magnetic materials such as the half-metallic ferromagnets, colossal-magnetoresistance materials, and ferromagnetic semiconductors will be mentioned. Also the challenges connected to the problem of spin transistor and spin manipulation will be discussed. (author)

  6. Prediction of molecular crystal structures

    International Nuclear Information System (INIS)

    The ab initio prediction of molecular crystal structures is a scientific challenge. Reliability of first-principle prediction calculations would show a fundamental understanding of crystallisation. Crystal structure prediction is also of considerable practical importance as different crystalline arrangements of the same molecule in the solid state (polymorphs)are likely to have different physical properties. A method of crystal structure prediction based on lattice energy minimisation has been developed in this work. The choice of the intermolecular potential and of the molecular model is crucial for the results of such studies and both of these criteria have been investigated. An empirical atom-atom repulsion-dispersion potential for carboxylic acids has been derived and applied in a crystal structure prediction study of formic, benzoic and the polymorphic system of tetrolic acid. As many experimental crystal structure determinations at different temperatures are available for the polymorphic system of paracetamol (acetaminophen), the influence of the variations of the molecular model on the crystal structure lattice energy minima, has also been studied. The general problem of prediction methods based on the assumption that the experimental thermodynamically stable polymorph corresponds to the global lattice energy minimum, is that more hypothetical low lattice energy structures are found within a few kJ mol-1 of the global minimum than are likely to be experimentally observed polymorphs. This is illustrated by the results for molecule I, 3-oxabicyclo(3.2.0)hepta-1,4-diene, studied for the first international blindtest for small organic crystal structures organised by the Cambridge Crystallographic Data Centre (CCDC) in May 1999. To reduce the number of predicted polymorphs, additional factors to thermodynamic criteria have to be considered. Therefore the elastic constants and vapour growth morphologies have been calculated for the lowest lattice energy structures

  7. Prediction of molecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, Theresa

    2001-07-01

    The ab initio prediction of molecular crystal structures is a scientific challenge. Reliability of first-principle prediction calculations would show a fundamental understanding of crystallisation. Crystal structure prediction is also of considerable practical importance as different crystalline arrangements of the same molecule in the solid state (polymorphs)are likely to have different physical properties. A method of crystal structure prediction based on lattice energy minimisation has been developed in this work. The choice of the intermolecular potential and of the molecular model is crucial for the results of such studies and both of these criteria have been investigated. An empirical atom-atom repulsion-dispersion potential for carboxylic acids has been derived and applied in a crystal structure prediction study of formic, benzoic and the polymorphic system of tetrolic acid. As many experimental crystal structure determinations at different temperatures are available for the polymorphic system of paracetamol (acetaminophen), the influence of the variations of the molecular model on the crystal structure lattice energy minima, has also been studied. The general problem of prediction methods based on the assumption that the experimental thermodynamically stable polymorph corresponds to the global lattice energy minimum, is that more hypothetical low lattice energy structures are found within a few kJ mol{sup -1} of the global minimum than are likely to be experimentally observed polymorphs. This is illustrated by the results for molecule I, 3-oxabicyclo(3.2.0)hepta-1,4-diene, studied for the first international blindtest for small organic crystal structures organised by the Cambridge Crystallographic Data Centre (CCDC) in May 1999. To reduce the number of predicted polymorphs, additional factors to thermodynamic criteria have to be considered. Therefore the elastic constants and vapour growth morphologies have been calculated for the lowest lattice energy

  8. Challenges for Inflationary Cosmology

    OpenAIRE

    Brandenberger, Robert H.

    2004-01-01

    Inflationary cosmology has provided a predictive and phenomenologically very successful scenario for early universe cosmology. Attempts to implement inflation using scalar fields, however, lead to models with serious conceptual problems. I will discuss some of the problems, explain why string theory could provide solutions to a subset of these problems, and give a brief overview of ``string gas cosmology'', one of the approaches to merge string theory and early universe cosmology.

  9. The ALICE Data Challenges

    CERN Document Server

    Baud, J P; Carminati, F; Collignon, M; Collin, F; Divià, R; Durand, J D; Jarp, S; Jouanigot, J M; Panzer, B; Rademakers, F; Saiz, P; Schossmaier, K; Van de Vyvre, P; Vascotto, Alessandro

    2001-01-01

    Since 1998, the ALICE experiment and the CERN/IT division have jointly executed several large-scale high throughput distributed computing exercises: the ALICE data challenges. The goals of these regular exercises are to test hardware and software components of the data acquisition and computing systems in realistic conditions and to execute an early integration of the overall ALICE computing infrastructure. This paper reports on the third ALICE Data Challenge (ADC III) that has been performed at CERN from January to March 2001. The data used during the ADC III are simulated physics raw data of the ALICE TPC, produced with the ALICE simulation program AliRoot. The data acquisition was based on the ALICE online framework called the ALICE Data Acquisition Test Environment (DATE) system. The data after event building were then formatted with the ROOT I/O package and a data catalogue based on MySQL was established. The Mass Storage System used during ADC III is CASTOR. Different software tools have been used to mo...

  10. Challenge Based Innovation gala

    CERN Document Server

    CERN. Geneva; Utriainen, Tuuli Maria; Toivonen, Harri; Nordberg, Markus

    2014-01-01

    Challenge Based Innovation gala   There’s a new experiment starting in CERN called IdeaLab where we work together with detector R&D researchers to help them to bridge their knowledge into a more human, societally oriented context. Currently we are located in B153, but will move our activities to a new facility next to the Globe in May 2014. One of our first pilot projects is a 5 month course CBI (Challenge Based Innovation) where two multidisciplinary student teams join forces with Edusafe & TALENT projects at CERN. Their goal is to discover what kind of tools for learning could be created in collaboration with the two groups. After months of user interviews and low resolution prototyping they are ready to share the results with us in the form of an afternoon gala. We warmly welcome you to join us to see the students' results and experience the prototypes they have conceived. The event is in three parts, you are welcome to visit all of them,...

  11. Proteomics Technologies and Challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

  12. The ALICE Data Challenges

    Institute of Scientific and Technical Information of China (English)

    J.P.Baud; W.Carena; 等

    2001-01-01

    Since 1998,the ALICE experiment and the CERN/IT division have jointly executed several large-scale high throughput distributed computing exercises:the ALICE data challenges.The goals of these regular exercises are to test hardware and software components of the data acqusition and computing systems in realistic conditions and to execute an early integration of the overall ALICE computing infrastructure.This paper reports on the third ALICE Data Challenge (ADC III) that has been performed at CERN from January to March 2001.The data used during the ADC Ⅲ are simulated physics raw data of the ALICE TPC,produced with the ALICE simulation program AliRoot.The data acquisition was based on the ALICE online framework called the ALICE Data Acquisition Test Environment (DATE) system.The data after event building,were then formatted with the ROOT I/O package and a data catalogue based on MySQl was established.The Mass Storage System used during ADC III is CASTOR.Different software tools have been used to monitor the performances,DATE has demonstrated performances of more than 500 MByte/s.An aggregate data throughput of 85 MByte/s was sutained in CASTOR over several days.The total collected data amounts to 100 TBytes in 100.00 files.

  13. Résultats challenge

    CERN Multimedia

    Club de pétanque

    2015-01-01

    C'est avec un temps magnifique que se disputait pour la deuxième année le Challenge de notre cher ami Patrick DURAND le jeudi 30 juillet 2015. Vingt-six personnes formées en doublettes s'affrontaient pour trois parties .Après des parties très serrées le juge arbitre Claude JOUVE épaulé par Alain PHILIPONA déclarait  vainqueur l'imbattable Claude MACARI suivi de très près par Eric DARMEDRU et à la troisième place Christian JOUVE. La première féminine était Mireille ROCHE. La soirée se clôturait par une succulente paëlla préparée par Jennifer et sa maman Sylvie JOUVE. Rendez-vous à tous pour le jeudi 27 août 2015 pour le challenge Jean-Claude FROT Nos concours sont ouverts à tous les amateurs de pétanque.

  14. Review - China's Environmental Challenges

    Directory of Open Access Journals (Sweden)

    Bill Bleisch

    2013-12-01

    Full Text Available Review of: Judith Shapiro. 2012. China's Environmental Challenges. Cambridge: UK and Malden, MA: Polity Press. Judith Shapiro's latest ambitious work picks up the story of modern China's checkered relationship with the environment at approximately the point where her previous study, Mao's War Against Nature (2001, left off. This latest book sets out to address questions of grave importance to China and to the world. The litany of challenges – poisonous water and toxic air, scarcity of water and other resources, deforestation, soil erosion, loss of biodiversity – seem nearly insurmountable, despite evidence of considerable attention from the Chinese government and from China's public, and despite the rocket-like rise of China's economic power and political influence in the world. Shapiro adds to this list the growing problems with lapses in environmental justice, both within China and passed on to its neighbours and to the countries with which it trades. Not only do growing environmental problems affect China's ability to achieve the government's stated goals of a 'harmonious society' with 'moderate prosperity for all,' but these problems, and the ways that ...

  15. Predicting chromatin organization using histone marks

    OpenAIRE

    Huang, Jialiang; Marco, Eugenio; Pinello, Luca; Yuan, Guo-Cheng

    2015-01-01

    Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these feat...

  16. Predicting Stock Market Returns by Combining Forecasts

    OpenAIRE

    Laurence Fung; Ip-wing Yu

    2008-01-01

    The predictability of stock market returns has been a challenge to market practitioners and financial economists. This is also important to central banks responsible for monitoring financial market stability. A number of variables have been found as predictors of future stock market returns with impressive in-sample results. Nonetheless, the predictive power of these variables has often performed poorly for out-of-sample forecasts. This study utilises a new method known as "Aggregate Forecast...

  17. Challenges in the Management of Older Patients with Colon Cancer

    OpenAIRE

    Dotan, Efrat; Browner, Ilene; Hurria, Arti; Denlinger, Crystal

    2012-01-01

    The majority of patients with colon cancer are over the age of 65. Their treatment poses multiple challenges to the oncologist, as these patients may have age-related comorbidities, polypharmacy, and physical or physiologic changes associated with older age. These challenges include limited data on the ability to predict tolerance to anti-cancer therapy and the appropriate use of treatment modalities in the setting of comorbidity and concurrent frailty. The low number of older patients enroll...

  18. Offshore northern Europe, the challenges

    International Nuclear Information System (INIS)

    This paper relates to challenges of the offshore activity in the North Sea. It is appropriate to address these challenges in the context of generating values through efficient management of resources, markets, safety and technology, as the challenges lie therein. The petroleum industry is built to turn natural resources into market value, assuring broad benefits to stake holders and shareholders. In the following, the challenges facing the industry the industry offshore Northern Europe is examined on this background

  19. WCET Tool Challenge 2011: Report

    OpenAIRE

    Bonenfant, Armelle; Cassé, Hugues; Bünte, Sven; Fellger, Wolfgang; Gepperth, Sebastian; Gustafsson, Jan; Huber, Benedikt; Islam, Nazrul Mohammad; Kästner, Daniel; Kirner, Raimund; Kovács, Laura; Krause, Felix; De Michiel, Marianne; Olesen, Mads Christian; Prantl, Adrian

    2011-01-01

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC’11) defined two kinds of problems to be solved by the Challenge participants with their tools, WCET problems, which ask for bounds on the execution time, and flow-analysis problems, which ask for bounds on the number ...

  20. Nuclear energy challenges in this Century

    International Nuclear Information System (INIS)

    The past fifty years have witnessed the advent of a new energy source and the beginning of yet another in the series of energy-use transitions that have marked our history since the start of our technological development. Each of these transitions has been accompanied by adaptive challenges. Each unique set of challenges has been met. Today the world faces the need for another transition. This paper outlines some of the associated challenges that lie ahead of us all, as we adapt to this new and exciting environment. The first step in defining the challenges ahead is to make some form of prediction of the future energy supply and demand during the period. Herein, the future up to 2010 is presumed to include two major events -- first, a decline in the availability and a rise in price of petroleum, and second a need to reduce greenhouse gases in our atmosphere. Both of these events are taken to be imminent. Added to these expected events is the assumption that the total of wind, solar, and other such energy sources will be able to contribute, but only in a relatively small way, to the provision of needed energy to our ever-expanding human population. (author)

  1. WCET Tool Challenge 2011: Report

    DEFF Research Database (Denmark)

    Bonenfant, Armelle; Cassé, Hugues; Bünte, Sven;

    2011-01-01

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC’11) defined two k...

  2. The WCET Tool Challenge 2011

    DEFF Research Database (Denmark)

    Hanxleden, Reinhard von; Holsti, Niklas; Lisper, Björn;

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC'11) dened two kin...

  3. The Biofilm Challenge

    DEFF Research Database (Denmark)

    Alhede, Maria; Alhede, Morten

    2014-01-01

    The concept of biofilms has emerged in the clinical setting during the last decade. Infections involving biofilms have been documented in all parts of the human body, and it is currently believed that the presence of biofilm-forming bacteria is equivalent to chronic infection. A quick Pubmed search...... reveals the significance of biofilms, as evidenced by a dramatic increase in scientific publications on the topic, as well as in publications concerning wounds with biofilms, which reached 600 publications in 2013. Judged from the number of publications, it appears that biofilms play a significant role in...... wounds. However, the impact of biofilms is often debated, because infected wounds were also treated before the concept of biofilms was coined. In this short review, we will address the significance of biofilms and their role in wounds, and discuss the future tasks of the biofilm challenge....

  4. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    VARMA S. K

    2013-01-01

    Full Text Available Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Improvement in knowledge in pharmacovigilance and communication from the top level to the grass-root level in the health sector will help in proper implementation of the programme. Patient should be educated to report any adverse effects after taking drug and stop relaying on acquiring information related to drugs in web. Proper detection, reporting and analysis would help to implement the programme for the betterment of society.

  5. Multicore Programming Challenges

    Science.gov (United States)

    Perrone, Michael

    The computer industry is facing fundamental challenges that are driving a major change in the design of computer processors. Due to restrictions imposed by quantum physics, one historical path to higher computer processor performance - by increased clock frequency - has come to an end. Increasing clock frequency now leads to power consumption costs that are too high to justify. As a result, we have seen in recent years that the processor frequencies have peaked and are receding from their high point. At the same time, competitive market conditions are giving business advantage to those companies that can field new streaming applications, handle larger data sets, and update their models to market conditions faster. The desire for newer, faster and larger is driving continued demand for higher computer performance.

  6. The Global Energy Challenge

    DEFF Research Database (Denmark)

    Connolly, David

    2011-01-01

    years. Afterwards, the security of the world’s energy supply is investigated and it becomes clear that there is both an inevitable shortage of fossil fuels and a dangerous separation of supply and demand. The final topic discussed is renewable energy, since it is one sustainable solution to the global......This report gives a brief overview of the global energy challenge and subsequently outlines how and where renewable energy could be developed to solve these issues. The report does not go into a lot of detail on these issues and hence, it is meant as an overview only. The report begins by outlining...... the causes of global climate change, concluding that energy-related emissions are the primary contributors to the problem. As a result, global energy production is analysed in more detail, discussing how it has evolved over the last 30 years and also, how it is expected to evolve in the coming 30...

  7. Sustainable Consumption: Research Challenges

    DEFF Research Database (Denmark)

    Reisch, Lucia A.; Cohen, Maurie J.; Thøgersen, John;

    policy) processes that are underway in Sweden and the rest of the European Union (EU) to tackle these challenges; ► to provide an overview of where the international research frontline is located and the status of Swedish research gaps in the area from an international perspective; ► to propose in detail......The Board of the Swedish Foundation for Strategic Environmental Research (Mistra) decided in October 2015 that a proposal for a funding application call in the research area of “sustainable consumption” should be drawn up. According to the statutes of Mistra, research funded by the foundation...... “shall promote the development of strong research environments of the highest international class with importance for Sweden’s future competitiveness. The research shall be of importance for finding solutions to important environmental problems and for a sustainable development of society. Opportunities...

  8. Media challenging capitalism

    DEFF Research Database (Denmark)

    Sandvik, Kjetil

    Digital media and especially so-called ‘social media’ have on the one hand been ascribed the power to change societies and empower democratic movements following the thoughts of e.g. Rheingold (2004), recently fueled by the democratic uprising in Arabic countries such as Egypt, Tunisia, Iran...... and communication research is currently engaging in a longer and deeper process of examining and assessing the cultural consequences of networked communication. One present challenge is to understand digital media and networked communication at the intersection of established and countercultural, utopian...... and dystopian trends in contemporary culture (Turner 2006). On that note, this paper examines the Occupy Wall Street-movement as an example on how social media with its democratic potential and its modes of communication through network structures – along with a variety of both historical and socio...

  9. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann;

    2015-01-01

    undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study was......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  10. Challenge Measurements For Authentication

    International Nuclear Information System (INIS)

    Authentication of systems with an information barrier that protects sensitive information is difficult; in particular, the information barrier can allow a hidden switch to be implemented by the system fabricator and operator. The hidden switch is the operator's ability to subvert the measurement system and force it to produce a desired and false result. It is usually discussed in the context of an attribute measurement in which a faked item is presented in place of a real item regulated by an agreement, with the driving motivation being the ability to preserve a stock of valuable items. In simple terms, the hidden switch enables a shell game with assets, and the information barrier protects the switch. This presentation outlines challenge measurements that could be used to detect the implementation of a hidden switch and assist the authentication process.

  11. Challenges of ecological restoration

    DEFF Research Database (Denmark)

    Halme, Panu; Allen, Katherine A.; Aunins, Ainars;

    2013-01-01

    The alarming rate of ecosystem degradation has raised the need for ecological restoration throughout different biomes and continents. North European forests may appear as one of the least vulnerable ecosystems from a global perspective, since forest cover is not rapidly decreasing and many...... Biological Diversity. Several northern countries are now taking up this challenge by restoring forest biodiversity with increasing intensity. The ecology and biodiversity of boreal forests are relatively well understood making them a good model for restoration activities in many other forest ecosystems. Here...... we introduce northern forests as an ecosystem, discuss the historical and recent human impact and provide a brief status report on the ecological restoration projects and research already conducted there. Based on this discussion, we argue that before any restoration actions commence, the ecology of...

  12. Predictable response from MCR operators

    International Nuclear Information System (INIS)

    Operating Philosophy in a nuclear power plant is the driving influence that leads to obtaining a predictable response to any operating challenge in the Main Control Room. This means that for any event or abnormal situation in the plant, every operator will take the unit to the required state, every time. This is a must in our industry. This can be achieved by clearly identifying the challenges that face the operating staff. It is essential that a balanced review be done so that there is not over emphasis on any aspect of the operator's ability to respond. The major areas discussed in this presentation are Plant, Procedures and People. Discussion will bring focus to the use of procedures and how to identify good practices that require reinforcement at the simulator, and how to identify potential vulnerabilities. The three overheads will be reviewed to illustrate the systematic approach used at Darlington Nuclear. (author)

  13. Advancement and prospect of short-term numerical climate prediction

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The defects of present methods of short-term numerical climate prediction are discussed in this paper, and four challenging problems are put forward. Considering our under developed computer conditions, we should innovate in the approcuch of numerical climate prediction on the basis of our own achievements and experiences in the field of short-term numerical climate prediction. It is possibly an effective way to settle the present defects of short-term numerical climate prediction.``

  14. New challenges in gas

    Energy Technology Data Exchange (ETDEWEB)

    Mandil, C. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France); Chabrelie, M.F. [Cedigaz, 92 - Rueil Malmaison (France); Streicher, C. [Prosernat, 92 - Paris la Defense (France)] [and others

    2003-07-01

    New developments in the area of gas treatment will be to a large extent driven by the need to find appropriate solutions to the fundamental need of sustainable development. New gas treatment processes are developed with the aim to minimise contaminant emissions and meet most stringent environmental specifications. A new major challenge for the industry will be to implement new cost effective technologies for reducing CO{sub 2} emissions. Industry has also to minimise its costs, and therefore, in order to ensure at the same time a better protection of the environment and a better safety, it is necessary to innovate. The purpose of this seminar is precisely to identify better the innovations which are required in the area of gas treatment. These proceedings comprise 8 papers and a summary of the contributions to a round-table discussion dealing with the options for CO{sub 2} capture and sequestration. The presentations treat of: the future prospects for the gas industry (M.F. Chabrelie, Cedigaz); the solutions for offshore gas treatment (C. Streicher, Prosernat); gas treatment with membranes (H. Meyer, GTI); the Axens Multibed{sub TM} technology for natural gas treatment (G. Jochem, Axens); the potentials and applications for the Propure co-current contactors (F.P. Nilsen, ProPure); the production of very-sour and super-sour large gas reserves: the new challenges (F. Lallemand, TotalFinaElf); Hybrisol, a new gas treatment process for sour natural gases (F. Lecomte, IFP); and the conception and building of large acid-gas removal units (J. Castel, Technip-Coflexip). (J.S.)

  15. Predicting protein structure classes from function predictions

    DEFF Research Database (Denmark)

    Sommer, I.; Rahnenfuhrer, J.; de Lichtenberg, Ulrik;

    2004-01-01

    We introduce a new approach to using the information contained in sequence-to-function prediction data in order to recognize protein template classes, a critical step in predicting protein structure. The data on which our method is based comprise probabilities of functional categories; for given......-to-structure prediction methods....

  16. Manufacturing Concepts of the Future – Upcoming Technologies Solving Upcoming Challenges

    DEFF Research Database (Denmark)

    Hadar, Ronen; Bilberg, Arne

    This paper presents an examination of Western European manufacturers’ future challenges as can be predicted today. Some of the challenges analyzed in the paper are: globalization, individualism and customization and agility challenges. Hereafter, the paper presents a broad analysis on manufacturing...... concepts and technologies that are being developed today which may be used to solve manufacturing challenges in the future, such as: (self) reconfigurable manufacturing systems, (focused) flexible manufacturing systems, and AI inspired manufacturing. The paper will try to offer a critical point of view...... on manufacturing challenges, concepts, and technologies, and is meant to address both academia and industry. Keywords: Reconfigurable manufacturing systems, manufacturing challenges, cognitive factory, mass-customization...

  17. Crowdsourcing for Challenging Technical Problems - It Works!

    Science.gov (United States)

    Davis, Jeffrey R.

    2011-01-01

    problems or challenges were posted through three different vendors: InnoCentive, yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive crowdsourcing platform designed for use internal to an organization and customized for NASA use, and promoted as NASA@Work. The results were significant. Of the seven InnoCentive external challenges, two full and five partial awards were made in complex technical areas such as predicting solar flares and long-duration food packaging.

  18. Algorithms for appliance usage prediction

    OpenAIRE

    Truong, Ngoc Cuong

    2014-01-01

    Demand-Side Management (DSM) is one of the key elements of future Smart Electricity Grids. DSM involves mechanisms to reduce or shift the consumption of electricity in an attempt to minimise peaks. By so doing it is possible to avoid using expensive peaking plants that are also highly carbon emitting. A key challenge in DSM, however, is the need to predict energy usage from specific home appliances accurately so that consumers can be notified to shift or reduce the use of high energy-consumin...

  19. Aviation turbulence processes, detection, prediction

    CERN Document Server

    Lane, Todd

    2016-01-01

    Anyone who has experienced turbulence in flight knows that it is usually not pleasant, and may wonder why this is so difficult to avoid. The book includes papers by various aviation turbulence researchers and provides background into the nature and causes of atmospheric turbulence that affect aircraft motion, and contains surveys of the latest techniques for remote and in situ sensing and forecasting of the turbulence phenomenon. It provides updates on the state-of-the-art research since earlier studies in the 1960s on clear-air turbulence, explains recent new understanding into turbulence generation by thunderstorms, and summarizes future challenges in turbulence prediction and avoidance.

  20. Predictability of Wave Energy and Electricity Markets

    DEFF Research Database (Denmark)

    Chozas, Julia Fernandez

    2012-01-01

    The articlw addresses an important challenge ahead the integration of the electricity generated by wave energy conversion technologies into the electric grid. Particularly, it looks into the role of wave energy within the day-ahead electricity market. For that the predictability of the theoretical...

  1. Predictive data mining in intensive care

    OpenAIRE

    Guiza Grandas, Fabian; Fierens, Daan; Ramon, Jan; Blockeel, Hendrik; Meyfroidt, Geert; Bruynooghe, Maurice; Van den Berghe , Greet

    2006-01-01

    In this paper we describe an application of data mining methods for different prediction tasks in an intensive care unit. Some of the challenging aspects of performing data mining in this domain are highlighted. The applied methods result in models with good performances within medical standards that can be valuable in assisting medical decision making.

  2. Making detailed predictions makes (some) predictions worse

    Science.gov (United States)

    Kelly, Theresa F.

    In this paper, we investigate whether making detailed predictions about an event makes other predictions worse. Across 19 experiments, 10,895 participants, and 415,960 predictions about 724 professional sports games, we find that people who made detailed predictions about sporting events (e.g., how many hits each baseball team would get) made worse predictions about more general outcomes (e.g., which team would win). We rule out that this effect is caused by inattention or fatigue, thinking too hard, or a differential reliance on holistic information about the teams. Instead, we find that thinking about game-relevant details before predicting winning teams causes people to give less weight to predictive information, presumably because predicting details makes information that is relatively useless for predicting the winning team more readily accessible in memory and therefore incorporated into forecasts. Furthermore, we show that this differential use of information can be used to predict what kinds of games will and will not be susceptible to the negative effect of making detailed predictions.

  3. Comprehensive adaptive mesh refinement in wrinkling prediction analysis

    OpenAIRE

    Selman, A.; Meinders, T.; Huetink, J.; Boogaard, van den, F.E.

    2002-01-01

    Discretisation errors indicator, contact free wrinkling and wrinkling with contact indicators are, in a challenging task, brought together and used in a comprehensive approach to wrinkling prediction analysis in thin sheet metal forming processes.

  4. Link prediction in complex networks: A survey

    Science.gov (United States)

    Lü, Linyuan; Zhou, Tao

    2011-03-01

    Link prediction in complex networks has attracted increasing attention from both physical and computer science communities. The algorithms can be used to extract missing information, identify spurious interactions, evaluate network evolving mechanisms, and so on. This article summaries recent progress about link prediction algorithms, emphasizing on the contributions from physical perspectives and approaches, such as the random-walk-based methods and the maximum likelihood methods. We also introduce three typical applications: reconstruction of networks, evaluation of network evolving mechanism and classification of partially labeled networks. Finally, we introduce some applications and outline future challenges of link prediction algorithms.

  5. Safeguards information challenges

    International Nuclear Information System (INIS)

    Full text: Overall, the aim of this paper is to provide the background and the broader vision in which the various information related presentations and posters proposed by the Department find their place, exploring solutions to the challenges faced. At a time when the Agency is expected to be a reference for the assessment of nuclear proliferation threats, providing the international community with independent, impartial, timely and credible conclusions that no declared nuclear material is diverted to non-peaceful purposes and that no undeclared nuclear material or activities exist in States, it has to address major challenges with regard to information. Drawing credible conclusions assumes that all relevant information is accessible and put into relevant context. Because of the legal constraints under which it operates, the limitation of resources for collecting existing but difficult to reach details and simply because of the overwhelming quantity of the information needed to properly evaluate proliferation issues, the Agency has to continually improve the way it collects, processes and internally disseminates safeguards relevant information. Developing a coherent picture of a State's nuclear capability is a complex process based on many experts' assessments and fusion of information. The search for better, broader and deeper information through dedicated collection processes is an ongoing effort aimed at filling the gaps of such pictures. Implementing well selected information collection tools is a sine qua non to render effective the Agency's detection capabilities. Beyond collection, another prerequisite to ensuring that the available information is accessible to those who need to know is the establishment of a proper information system architecture and an efficient set of standard business processes. At the same time, that information must be sufficiently protected by appropriate security measures, particularly at a time when private hacking has become a

  6. Safeguards information challenges

    International Nuclear Information System (INIS)

    The purpose of this paper is to provide the background and broader vision in which the various presentations and posters on information related matters, prepared by staff of the Department of Safeguards, find their place, exploring solutions to the challenges faced. At a time when the IAEA is expected to be a reference for the assessment of nuclear proliferation issues, it faces major challenges with regard to the information needed to provide the international community with independent, impartial, timely and soundly based conclusions regarding the non-diversion of declared nuclear material and the absence of undeclared nuclear material or activities in States. The drawing of such conclusions assumes that all relevant information is accessible and has been put in the relevant context. Unfortunately, because of legal constraints under which it operates, or because of limitations on resources available for collecting existing but difficult to reach facts, or simply because of the overwhelming aspect of the information needed to properly evaluate proliferation issues, the IAEA needs to enhance the way it collects, processes, analyses, evaluates and disseminates safeguards relevant information. The search for better, broader and deeper information through dedicated collection means is an ongoing effort aimed at filling the gaps that constrain the development of the coherent picture that analysts need to be comfortable with the results of complex analyses. Implementation of well-selected information collection tools is sine qua non for effective IAEA verification capabilities. Beyond collection, the establishment of a proper information architecture and documented business processes is a prerequisite for ensuring that the available information is accessible to those with a need to know. At the same time, information must be sufficiently protected by appropriate security measures, particularly when hacking has become an intellectual sport and institutional security

  7. Osteomyelitis: a current challenge

    Directory of Open Access Journals (Sweden)

    Luciana Souza Jorge

    2010-06-01

    Full Text Available Over the last 30 years, the pathogenesis of osteomyelitis has almost been totally elucidated, and many factors responsible for the persistence of this infection have been identified. Numerous antimicrobial agents with distinct spectrums of action, pharmacokinetics, and pharmacodynamics have been used in its treatment. Surgical techniques, including muscle grafts, the Ilizarov technique, and antibiotic bone cements, have been applied. However, bone infections are still a challenge. Despite the importance of isolation and identification of microorganisms to determine the antimicrobial treatment of bone infections, there are few systematic national studies about the etiological profile of these diseases. This article describes the current knowledge of osteomyelitis and summarizes published national data based on the experience of different Orthopedic and Traumatology Services. In general, S. aureus was described as an important etiological agent; however, the difference in design of national studies makes a comparison between the prevalence of bone infection, the associated risk factors, and the different therapeutic approaches difficult. In conclusion, effort is necessary in order to stimulate systematic national studies in different Orthopedics and Traumatology Services to obtain a better consensus on preventive measures and therapies of bone infections.

  8. VISIR: Experiences and Challenges

    Directory of Open Access Journals (Sweden)

    Mohamed Tawfik

    2012-02-01

    Full Text Available It is of crucial importance the integration of practical sessions in engineering curricula owing to their significant role in understanding engineering concepts and scientific phenomena. However, the lack of practical sessions due to the high costs of the equipment and the unavailability of instructors has caused a significant declination in experimentation in engineering education. Remote laboratories have tackled this issues providing online reusable and shared workbenches unconstrained by neither geographical nor time considerations. Thereby, they have extremely proliferated among universities and integrated into engineering curricula over the last decade. This contribution compiles diverse experiences based on the deployment of the remote laboratory, Virtual Instrument Systems in Reality (VISIR, on the practices of undergraduate engineering grades at various universities within the VISIR community. It aims to show the impact of its usage on engineering education concerning the assessments of students and teachers as well. In addition, the paper address the next challenges and future works carried out at several universities within the VISIR community.

  9. Challenges in organ transplantation.

    Science.gov (United States)

    Beyar, Rafael

    2011-04-01

    Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty. PMID:23908807

  10. Challenges in Organ Transplantation

    Directory of Open Access Journals (Sweden)

    Rafael Beyar

    2011-04-01

    Full Text Available Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty.

  11. [Geriatrics - an interdisciplinary challenge].

    Science.gov (United States)

    Nau, Roland; Djukic, Marija; Wappler, Manfred

    2016-06-01

    The care of elderly patients will continue to challenge the healthcare system over the next decades. As a rule geriatric patients suffer from multimorbidities with complex disease patterns, and the ability to cope with everyday life is severely reduced. Treatment is provided by a multiprofessional geriatric team, and the primary goal is improvement of functional status, quality of life in the social environment and autonomy by employing a holistic approach. In Germany geriatric care is provided by physicians from various medical specialties (e.g. general practitioners, internists, neurologists and psychiatrists). In the training for the subspecialty clinical geriatrics, these specialties enjoy equal rights. Recent efforts to establish a qualification as physician for internal medicine and geriatrics have initiated a discussion to make the suitability for qualification as a geriatrician dependent on the medical specialty. Geriatric patients benefit from multidisciplinary cooperation. Neurologists possess great expertise in the treatment of patients with dementia, depression, delirium, consequences of degenerative spinal cord diseases and vertebral bone fractures, stroke, Parkinson's syndrome, epileptic seizures, vertigo and dizziness, neuropathies, lesions of peripheral nerves and in the multimodal therapy of pain. To function in a position of responsibility in a geriatric department, neurologists need skills in general internal medicine. These are acquired either on a geriatric ward or during specialization as a neurologist by full time secondment to large neurological or interdisciplinary intensive care units. PMID:27167886

  12. Opportunities and challenges ahead

    International Nuclear Information System (INIS)

    Achievements of the natural gas industry during the past 11 years, since the beginning of deregulation, have been reviewed. The period has been characterized as a decade of rapid growth, almost entirely due to exports, which more than tripled from 740 BCF in 1986 to 2,810 BCF in 1996. Two major pipeline projects, the Iroquois project to the U.S. Northeast in 1991, followed by the massive PGT expansion to markets in southern California and the Pacific Northwest, were the prime facilitators of this unprecedented growth. At present, and for the immediate future, expansion of the market is stalled due the lack of major pipeline expansions. Only modest expansions are planned for the 1995-1998 period, when the Northern Border expansion is scheduled to begin. Thus, excess deliverability (resulting from record drilling levels in the mid-1990s), and a pressing need for additional pipeline capacity constitute the principal challenges for the immediate future. In the longer term, prospects are encouraging, with a number of major pipeline projects ahead, including a 1.2BCF/day line from northern Alberta to the U.S. Midwest, the Palliser project to ship 1BCF/day from southern Alberta to the Alberta border, the Nexus project, an expansion of the TransCanada Pipelines to the U.S. Midwest, and the Sable Island project on the East Coast to bring eastern Canadian natural gas to Canada's heartland. Overall, the long-term prospects are very good, indeed

  13. Challenges in Piaget's legacy.

    Science.gov (United States)

    Bibace, Roger

    2013-03-01

    The publication of After Piaget (Martí and Rodríguez 2012) hopefully triggers a new effort to understand the richness of the efforts of that major psychologist of the 20th century. Piaget was consistently concerned with part/whole relationships throughout his life. He addressed this issue philosophically, epistemologically, and psychologically. Conceptually Piaget struggled with the issue of continuity/discontinuity in development and changed his mind about how to reconcile the discontinuities of stages with his concept of development. I also attribute his variability to the implications of his important work on perception, and to his willingness to get involved in widespread concrete applications of his approach to education including the education of children with special needs; his center for genetic epistemology, and his interest in psychoanalysis. Benefiting from all the authors of After Piaget, I want to point out that Piaget has identified many major issues that will continue to constitute challenges to psychology in this century. These include specifying terms such as 'development;' methodological issues such as sampling both quantitatively in one culture and across cultures; comprehensive inclusion of the psychological processes covered by introductory textbooks in psychology; and conceptual issues such as the relationships among all these parts within a whole. I make a distinction between an 'issue' and a 'problem'--problems have solutions; while issues refer to controversies in science generally as well as in psychology that have persisted for centuries. PMID:22733313

  14. 'Scrap yard challenge'

    International Nuclear Information System (INIS)

    'Plutonium'. The word evokes deep reactions outside of the nuclear industry. Although the majority of Plutonium currently in existence is man-made and therefore perceived as being unnatural, plutonium has been found as a product of the Oklo natural reactor in Gabon. This paper seeks to challenge two concepts, that of the Nuclear Control Institute that Plutonium is unnatural, 'fiendishly toxic' and one of the 'substances most hazardous to man' and the second image that a high security Plutonium store is merely a 'scrapyard' containing a material which has little use. The nuclear industry has often been accused of treating Plutonium and its accumulation casually in proportion to the risks perceived by those outside the industry. As a result this paper seeks to demonstrate that the industry is aware of the concerns of the public and is actively seeking viable solutions. The paper looks at Plutonium itself and explores the issues surrounding military and civil Plutonium in adding to the current stockpiles. It also suggests three possible alternatives for dealing with these Plutonium stockpiles and arrives at a conclusion as to which solutions currently appear most viable. (authors)

  15. Physician Challenges in 2015.

    Science.gov (United States)

    Cascardo, Debra

    2015-01-01

    While the influx of new patients resulting from the ACA will increase the number of people receiving healthcare, the regulations associated with it will add to physicians' administrative duties, as will government regulations associated with HIPAA and Meaningful Use. Further stress will come from the demands of both payers and patients, requiring doctors to walk a fine line to protect themselves from litigation. Technology also will play an increasing role. The continuing move toward EHRs and the new ICD-10 coding standard will require investments in software, testing, and training staff, and may also require an investment in new computer hardware. Physicians and staff will have to teach patients how to use EHR portals and how to follow the record-keeping requirements of their insurance providers. The regulatory changes and increased costs of time and money associated with them may drive many physicians out of private practice and into hospital system-based team practices, which will face a greater challenge in recruiting and retaining top talent. Other physicians, in contrast, may continue to seek the independence of private practice; some of them may decide to stop accepting insurance because of their need for autonomy in their practices. Regardless of what decisions doctors choose to make within the changing nature of healthcare, it is important to keep abreast of the changes and develop a plan for dealing with them, in 2015 and beyond. PMID:26182706

  16. Challenges in Astronomy Education

    Science.gov (United States)

    De Greve, Jean-Pierre

    2010-11-01

    Astronomy is an attractive subject for education. It deals with fascination of the unknown and the unreachable, yet is uses tools, concepts and insights from various fundamental sciences such as mathematics, physics, chemistry, biology. Because of this it can be well used for introducing sciences to young people and to raise their interest in further studies in that direction. It is also an interesting subject for teaching as its different aspects (observation techniques, theory, data sampling and analysis, modelling,?) offer various didactical approaches towards different levels of pupils, students and different backgrounds. And it gives great opportunities to teach and demonstrate the essence of scientific research, through tutorials and projects. In this paper we discuss some of the challenges education in general, and astronomy in particular, faces in the coming decades, given the major geophysical and technological changes that can be deducted from our present knowledge. This defines a general, but very important background in terms of educational needs at various levels, and in geographical distribution of future efforts of the astronomical community. Special emphasis will be given to creative approaches to teaching, to strategies that are successful (such as the use of tutorials with element from computer games), and to initiatives complementary to the regular educational system. The programs developed by the IAU will be briefly highlighted.

  17. Downstream prediction using a nonlinear prediction method

    Science.gov (United States)

    Adenan, N. H.; Noorani, M. S. M.

    2013-11-01

    The estimation of river flow is significantly related to the impact of urban hydrology, as this could provide information to solve important problems, such as flooding downstream. The nonlinear prediction method has been employed for analysis of four years of daily river flow data for the Langat River at Kajang, Malaysia, which is located in a downstream area. The nonlinear prediction method involves two steps; namely, the reconstruction of phase space and prediction. The reconstruction of phase space involves reconstruction from a single variable to the m-dimensional phase space in which the dimension m is based on optimal values from two methods: the correlation dimension method (Model I) and false nearest neighbour(s) (Model II). The selection of an appropriate method for selecting a combination of preliminary parameters, such as m, is important to provide an accurate prediction. From our investigation, we gather that via manipulation of the appropriate parameters for the reconstruction of the phase space, Model II provides better prediction results. In particular, we have used Model II together with the local linear prediction method to achieve the prediction results for the downstream area with a high correlation coefficient. In summary, the results show that Langat River in Kajang is chaotic, and, therefore, predictable using the nonlinear prediction method. Thus, the analysis and prediction of river flow in this area can provide river flow information to the proper authorities for the construction of flood control, particularly for the downstream area.

  18. Challenges in publication ethics.

    Science.gov (United States)

    Barbour, V; Astaneh, B; Irfan, M

    2016-04-01

    skill. Finally, the editor needs to deal with the journal's ethical policy when examples of plagiarism, author disputes or other forms of misconduct are evident. Breaches of publication ethics are forms of scientific misconduct that can undermine science and challenge editors, many of whom have little formal training in this field. In this respect, the Committee on Publication Ethics (COPE), founded in 1997 as a voluntary body, has become a central player. COPE provides a discussion forum and advice as well as guidelines for scientific editors with the aim of finding practical ways to deal with forms of misconduct. The Annals is a member of COPE and follows its code of conduct for journal editors. (2) It is a privilege that the current chair of COPE, Dr Barbour, and her colleagues have written this final article in the medical publishing series about challenges in publication ethics. I hope you have found this series useful and enjoyed reading the range of articles we have published from many experts in their fields. JYOTI SHAH Commissioning Editor References 1. Sanders SA , Reinisch JM . Would you say you 'had sex' if…? JAMA 1999 ; 281 : 275 - 277 . 2. Committee on Publication Ethics . Code of Conduct and Best Practice Guidelines for Journal Editors . Harleston, UK : COPE ; 2011 . PMID:26985812

  19. Cognitive and affective components of challenge and threat states.

    Science.gov (United States)

    Meijen, Carla; Jones, Marc V; McCarthy, Paul J; Sheffield, David; Allen, Mark S

    2013-01-01

    We explored the cognitive and affective components of the Theory of Challenge and Threat States in Athletes (TCTSA) using a cross-sectional design. One hundred and seventy-seven collegiate athletes indicated how they typically approached an important competition on measures of self-efficacy, perceived control, achievement goals, emotional states and interpretation of emotional states. Participants also indicated to what extent they typically perceived the important competition as a challenge and/or a threat. The results suggest that a perception of challenge was not predicted by any of the cognitive components. A perception of threat was positively predicted by avoidance goals and negatively predicted by self-efficacy and approach goals. Both challenge and threat had a positive relationship with anxiety. Practical implications of this study are that an avoidance orientation appeared to be related to potentially negative constructs such as anxiety, threat and dejection. The findings may suggest that practitioners and researchers should focus on reducing an avoidance orientation, however the results should be treated with caution in applied settings, as this study did not examine how the combination of constructs exactly influences sport performance. The results provided partial support for the TCTSA with stronger support for proposed relationships with threat rather than challenge states. PMID:23256682

  20. The stem factor challenge

    International Nuclear Information System (INIS)

    One of the most important challenges that still needs to be met in the effort to understand the operation of motor-operated, rising-stem valves is the ability to determine stem factor throughout the valve's load range. The stem factor represents the conversion of operator torque to stem thrust. Determining the stem factor is important because some motor-operated valves (MOVs) cannot be tested in the plant at design basis conditions. The ability of these valves to perform their design basis function (typically, to operate against specified flow and pressure loads) must be ensured by analytical methods or by extrapolating from the results of tests conducted at lower loads. Because the stem factor tends to vary in response to friction and lubrication phenomena that occur during loading and wedging, analytical methods and extrapolation methods have been difficult to develop and implement. Early investigations into variability in the stem factor tended to look only at the tip of the iceberg; they focused on what was happening at torque switch trip, which usually occurs at full wedging. In most stems, the stem factor is better (lower) in the wedging transient than before wedging, so working with torque switch trip data alone led many early researchers to false conclusions about the relationship between stem factor and load. However, research at the Idaho National Engineering Laboratory (INEL) has taken a closer look at what happens during the running portion of the closing stroke along with the wedging portion. This shift in focus is important, because functional failure of a valve typically consists of a failure to isolate flow, not a failure to achieve full wedging. Thus, the stem factor that must be determined for a valve's design basis closing requirements is the one that corresponds with the running load before wedging

  1. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-12-01

    Full Text Available ABSTRACT IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  2. WANO. Development, programs, challenges

    International Nuclear Information System (INIS)

    In the wake of the accident at the Soviet RBMK reactor unit 4 in Chernobyl the nuclear industry founded the World Association of Nuclear Operators (WANO). To this day, the purpose of the organization has been to enhance worldwide cooperation of nuclear industry and, in this way, strengthen the safety and availability of nuclear power plants. Following some first steps after 1986, the charter of the organization was signed at the WANO constituent assembly in Moscow on May 15 and 16, 1989. The member companies thus committed themselves to support WANO's mission. WANO was established for these purposes: ''The mission of WANO is to maximize the safety and reliability of nuclear power plants worldwide by working together to assess, benchmark and improve performance through mutual support, exchange of information, and emulation of best practices.'' The WANO programs developed speedily thereafter. The focus was on peer reviews. In 2000, the first interim objective had been reached: Fifty percent of all member nuclear power plants had undergone peer reviews. In addition, plant-related peer reviews were extended throughout all operator organizations, and corporate peer reviews were developed. The other WANO programs as well, i.e. exchanges of experience, technical support, and performance indicators, exerted more and more influence on industry. Peer reviews covered entire operator organizations, and corporate peer reviews were developed. The worldwide paradigm shift in evaluating the use of nuclear power, and the associated construction programs for new nuclear power plants already in their implementation phase, assigned a new quality to the work of WANO. The organization is preparing a long-term strategy in the face of the challenges to be expected. The ultimate objective of these efforts is to support member organizations from the first preparations of a nuclear power plant project to the end of commercial operation. (orig.)

  3. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-10-01

    Full Text Available IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  4. The WCET Tool Challenge 2011

    OpenAIRE

    Hanxleden, Reinhard von; Holsti, Niklas; Lisper, Björn; Gustafsson, Jan; Islam, Nazrul Mohammad; Ploedereder, Erhard; Fellger, Wolfgang; Gepperth, Sebastian; Krause, Felix; Wilhelm, Reinhard; Bonenfant, Armelle; Casse, Hugues; De Michiel, Marianne; Rochange, Christine; Bünte, Sven

    2012-01-01

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC'11) dened two kinds of problems to be solved by the Challenge participants with their tools, WCET problems, which ask for bounds on the execution time, and ow-analysis problems, which ask for bounds on the number of t...

  5. The challenges of green nanotechnology

    OpenAIRE

    Miguel de la Guardia

    2014-01-01

    Nanomaterials have great impacts on life sciences; however, these advanced materials may induce inadvertant consequences. Thus, this editorial will highlight the futuristic challenges ingreen nanotechnology.

  6. Challenges and Opportunities

    International Nuclear Information System (INIS)

    A series of overhead viewgraphs accompanied this presentation. The viewgraphs presented 1998 year-end predictions of oil and gas prices. Comparisons of projected versus actual values for 1998 for natural gas consumption, production, imports and wellhead prices for the United States were also presented. A comparison of projected versus actual consumption values for 1998 in the residential, commercial, industrial and electric generation sectors was included. In many cases actual versus projected values were quite different. The importance of storage to balancing the market was illustrated. Graphs depicting gas production, workover rigs, reserve life comparisons, and GOM natural gas rig count and production for the U.S. were described. Drilling activity in the Gulf of Mexico was summarized. The total wells drilled in 1997 was 1223 compared to 1019 in 1998. The factors affecting deliverability additions on the Gulf of Mexico shelf include smaller new discoveries, diminishing completion opportunities in older fields, few productive zones in new discoveries and a rapid decline rate resulting from smaller reservoirs. 6 tabs., 13 figs

  7. Powering nanorobotic devices: challenges and future strategies

    Science.gov (United States)

    Sankar, Krishna Moorthi

    2014-04-01

    Nanotechnology, even after 55 years since its foundation (1959 Richard Feynman's speech - `There is lot of space in the bottom'), is still in its infancy. However, of late, there has been a large increase in the research being done in this field in many prominent Universities and Research institutions across the globe. Nanorobotics is the combination of Nanotechnology and the science of Robotics, to create robots that are only a few nanometres (10-9 metres) in size. Nanobots are yet to be made. But with the current pace of ongoing researches, scientists predict that nanobots will be made a reality by next ten years. The main proposed function of nanobots is to use them in the medical field to interact with cells or intra-cellular substances and prevent or reverse structural and genetical problems and diseases. One of the major challenges faced while creating a nanobot to travel through human body is to power it. Nanobots would require a very small yet highly potential source of energy. There are many hypothesised energy sources for nanobots which are either already available within the human body naturally or which are to be supplied externally. But, all of these energy sources pose a few challenges which need to be addressed if they are to be used to power nanobots. These challenges can be overcome using a number of strategies that can be used to make an economically, ecologically and medically viable energy source.

  8. Learning predictive clustering rules

    OpenAIRE

    Ženko, Bernard; Džeroski, Sašo; Struyf, Jan

    2005-01-01

    The two most commonly addressed data mining tasks are predictive modelling and clustering. Here we address the task of predictive clustering, which contains elements of both and generalizes them to some extent. We propose a novel approach to predictive clustering called predictive clustering rules, present an initial implementation and its preliminary experimental evaluation.

  9. The challenges of fusion

    International Nuclear Information System (INIS)

    The new boss of the world's biggest fusion experiment cannot afford to fail. Kaname Ikeda will soon be a name on many physicists' lips. Though the outgoing Japanese ambassador to Croatia and former science administrator is not currently widely known, that will all change when he starts work later this month as director general of the International Thermonuclear Experimental Reactor (ITER). Set to be built at Cadarache near Marseille in southern France - assuming the ITER treaty is ratified - this Euro10bn facility is designed to show that fusion could be turned into a practical energy source.To do so would be huge achievement. Fusion reactors could play a massive role in meeting the world's rapidly growing demand for energy. They promise to be environmentally friendly and relatively safe to operate, while the raw materials they need are plentiful. However, early progress in fusion research led plasma physicists to be over optimistic about this energy source, and a commercial fusion plant remains as far off in the future as it was back in the 1970s. Ikeda therefore has a tough job on his hands, as he readily admits in our interview with him (see p12; print version only). It will be no mean feat to build ITER on time and to budget, and Ikeda will have to draw heavily on his undoubted diplomatic skills to ensure that everyone involved in this complex international project gets on. ITER is hugely ambitious in engineering terms, with vast superconducting magnets needed to confine a deuterium-tritium plasma within a doughnut-shaped 'tokamak' vessel. Numerous technical challenges will have to be addressed to ensure ITER fulfils its goal of releasing more energy than it consumes. These include choosing which material to line the inner wall of the tokamak with, overcoming the accumulation of radioactive tritium on this surface, and controlling the properties of the plasma. Fortunately, such issues are being addressed at the recently upgraded Joint European Torus near Oxford

  10. Nonparametric bootstrap prediction

    OpenAIRE

    Fushiki, Tadayoshi; Komaki, Fumiyasu; Aihara, Kazuyuki

    2005-01-01

    Ensemble learning has recently been intensively studied in the field of machine learning. `Bagging' is a method of ensemble learning and uses bootstrap data to construct various predictors. The required prediction is then obtained by averaging the predictors. Harris proposed using this technique with the parametric bootstrap predictive distribution to construct predictive distributions, and showed that the parametric bootstrap predictive distribution gives asymptotically better prediction tha...

  11. Predictability of social interactions

    OpenAIRE

    Xu, Kevin S.

    2013-01-01

    The ability to predict social interactions between people has profound applications including targeted marketing and prediction of information diffusion and disease propagation. Previous work has shown that the location of an individual at any given time is highly predictable. This study examines the predictability of social interactions between people to determine whether interaction patterns are similarly predictable. I find that the locations and times of interactions for an individual are...

  12. Challenges in Computational Commutative Algebra

    OpenAIRE

    Abbott, John

    2006-01-01

    In this paper we consider a number of challenges from the point of view of the CoCoA project one of whose tasks is to develop software specialized for computations in commutative algebra. Some of the challenges extend considerably beyond the boundary of commutative algebra, and are addressed to the computer algebra community as a whole.

  13. IT Challenges for Space Medicine

    Science.gov (United States)

    Johnson-Throop, Kathy

    2010-01-01

    This viewgraph presentation reviews the various Information Technology challenges for aerospace medicine. The contents include: 1) Space Medicine Activities; 2) Private Medical Information; 3) Lifetime Surveillance of Astronaut Health; 4) Mission Medical Support; 5) Data Repositories for Research; 6) Data Input and Output; 7) Finding Data/Information; 8) Summary of Challenges; and 9) Solutions and questions.

  14. Organizational leadership: meeting the challenge.

    Science.gov (United States)

    Hart, A L

    1994-06-01

    Leadership can be learned. Knowledge of leadership theories can serve as basis for developing skills and techniques. Style, trait, and transformational leadership can be applied in both health care institutions and professional associations. Organizational leadership is challenging, but those challenges can help individual nurses grow in the leadership skills that will continue to be demanded in the ever changing healthcare arena. PMID:8075165

  15. Challenges Facing Group Work Online

    Science.gov (United States)

    Chang, Bo; Kang, Haijun

    2016-01-01

    Online group work can be complicated because of its asynchronous characteristics and lack of physical presence, and its requirements for skills in handling technology, human relationships, and content-related tasks. This study focuses on the administrative, logistical and relationship-related challenges in online group work. Challenges in areas…

  16. A Window-Washing Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    Skyscrapers sure do have a lot of windows, and these windows are cleaned and checked regularly. All this takes time, money, and puts workers at potential risk. Might there be a better way to do it? In this article, the author discusses a window-washing challenge and describes how students can tackle this task, pick up the challenge, and creatively…

  17. Higher Education Marketing: A Challenge.

    Science.gov (United States)

    Canterbury, Richard

    1999-01-01

    States that similarities between education and other services may not be sufficient to conclude that services marketing methods can be easily transferred to all markets in higher education. Article identifies and discusses why higher education marketing is a particular challenge. Suggests that understanding these challenges can help in making…

  18. Challenges When Introducing Electronic Exam

    Science.gov (United States)

    Kuikka, Matti; Kitola, Markus; Laakso, Mikko-Jussi

    2014-01-01

    Time pressures often necessitate the use of more efficient exam tools, such as electronic exams (e-exams), instead of traditional paper exams. However, teachers may face challenges when introducing e-exams in a higher education context. This paper describes what kinds of challenges teachers may face when introducing e-exams, based on experiences…

  19. Five Biggest Challenges for 2002.

    Science.gov (United States)

    Ishizuka, Kathy; Minkel, Walter; St. Lifer, Evan

    2002-01-01

    Addresses five themes that represent school librarians' overriding challenges for the year 2002: gaining the respect of school administrators; making information literacy a higher priority; recruiting new librarians to meet the growing demand; dealing with fiscal uncertainty in a recession; and the challenge of accessing information in a filtered…

  20. Adaptive challenges in medical practices.

    Science.gov (United States)

    Daiker, Barbara L

    2013-01-01

    The purpose of this qualitative grounded theory study was to describe the theoretical structures of the strategies used by medical practices to navigate adaptive challenges. The process of responding to adaptive challenges in five medical practices was studied using a grounded theory approach, collecting data from interviews with the organizations' leaders and managers. The leadership of these medical practices had successfully navigated adaptive challenges within two years of the study. The analysis revealed a model that describes the key elements in finding solutions to adaptive challenges. The model was named the Adaptation Solution Dynamic, which explains the elements of Rational Tools, Relationship Commitment, and Achievement Drive. The findings from the results of this study provide a theoretical basis for studying how leaders support identifying solutions to adaptive challenges. PMID:23866647

  1. Predicting ecosystem stability from community composition and biodiversity

    NARCIS (Netherlands)

    Mazancourt, C.; Isbell, F.; Larocque, A.; Berendse, F.; Ruijven, van J.

    2013-01-01

    As biodiversity is declining at an unprecedented rate, an important current scientific challenge is to understand and predict the consequences of biodiversity loss. Here, we develop a theory that predicts the temporal variability of community biomass from the properties of individual component speci

  2. Predictive Technologies: Can Smart Tools Augment the Brain's Predictive Abilities?

    Science.gov (United States)

    Pezzulo, Giovanni; D'Ausilio, Alessandro; Gaggioli, Andrea

    2016-01-01

    The ability of "looking into the future"-namely, the capacity of anticipating future states of the environment or of the body-represents a fundamental function of human (and animal) brains. A goalkeeper who tries to guess the ball's direction; a chess player who attempts to anticipate the opponent's next move; or a man-in-love who tries to calculate what are the chances of her saying yes-in all these cases, people are simulating possible future states of the world, in order to maximize the success of their decisions or actions. Research in neuroscience is showing that our ability to predict the behavior of physical or social phenomena is largely dependent on the brain's ability to integrate current and past information to generate (probabilistic) simulations of the future. But could predictive processing be augmented using advanced technologies? In this contribution, we discuss how computational technologies may be used to support, facilitate or enhance the prediction of future events, by considering exemplificative scenarios across different domains, from simpler sensorimotor decisions to more complex cognitive tasks. We also examine the key scientific and technical challenges that must be faced to turn this vision into reality. PMID:27199648

  3. Numerical earthquake prediction

    International Nuclear Information System (INIS)

    Can earthquakes be predicted? How should people overcome the difficulties encountered in the study of earthquake prediction? This issue can take inspiration from the experiences of weather forecast. Although weather forecasting took a period of about half a century to advance from empirical to numerical forecast, it has achieved significant success. A consensus has been reached among the Chinese seismological community that earthquake prediction must also develop from empirical forecasting to physical prediction. However, it is seldom mentioned that physical prediction is characterized by quantitatively numerical predictions based on physical laws. This article discusses five key components for numerical earthquake prediction and their current status. We conclude that numerical earthquake prediction should now be put on the planning agenda and its roadmap designed, seismic stations should be deployed and observations made according to the needs of numerical prediction, and theoretical research should be carried out. (authors)

  4. Predictive modeling of complications.

    Science.gov (United States)

    Osorio, Joseph A; Scheer, Justin K; Ames, Christopher P

    2016-09-01

    Predictive analytic algorithms are designed to identify patterns in the data that allow for accurate predictions without the need for a hypothesis. Therefore, predictive modeling can provide detailed and patient-specific information that can be readily applied when discussing the risks of surgery with a patient. There are few studies using predictive modeling techniques in the adult spine surgery literature. These types of studies represent the beginning of the use of predictive analytics in spine surgery outcomes. We will discuss the advancements in the field of spine surgery with respect to predictive analytics, the controversies surrounding the technique, and the future directions. PMID:27286683

  5. Location Prediction Optimisation in Wireless Sensor Networks Using Kriging Interpolation

    OpenAIRE

    Ali, A; Ikpehai, A.; Adebisi, B.; Mihaylova, L.S.

    2016-01-01

    Many wireless sensor network (WSN) applications rely on precise location or distance information. Despite the potentials of WSNs, efficient location prediction is one of the subsisting challenges. This paper presents novel prediction algorithms based on a Kriging interpolation technique. Given that each sensor is aware of its location only, the aims of this work are to accurately predict the temperature at uncovered areas and estimate positions of heat sources. By taking few measurements with...

  6. CNX PSU Bank Index Prediction Using Soft Computing - A Study

    OpenAIRE

    J. Mary Dallfin Bruxella; S. Arun Joe Babulo

    2013-01-01

    Stock markets are incredible systems wherein thousands of stocks, ETFs and bonds are traded bymillions of traders every day, around the world, in a never-ending battle to make money. Predicting stockmarkets has been one of the biggest challenges of the AI community since about two decades ago. Theobjective of this paper is to review the previous methods used for prediction and the proposed method. Theaim of this work is to predict the National Stock Exchange (NSE) market PSU Bank Index value ...

  7. Stock Price Change Rate Prediction by Utilizing Social Network Activities

    OpenAIRE

    Shangkun Deng; Takashi Mitsubuchi; Akito Sakurai

    2014-01-01

    Predicting stock price change rates for providing valuable information to investors is a challenging task. Individual participants may express their opinions in social network service (SNS) before or after their transactions in the market; we hypothesize that stock price change rate is better predicted by a function of social network service activities and technical indicators than by a function of just stock market activities. The hypothesis is tested by accuracy of predictions as well as pe...

  8. How to Establish Clinical Prediction Models.

    Science.gov (United States)

    Lee, Yong Ho; Bang, Heejung; Kim, Dae Jung

    2016-03-01

    A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice. PMID:26996421

  9. The Leadership Challenge Activities Book

    CERN Document Server

    Kouzes, James M; Biech, Elaine

    2010-01-01

    ACTIVE Learning for Exemplary Leaders. The best leaders are the best learners. This evidence-based truth has been a foundational principle of The Leadership Challenge since it was first published nearly twenty-five years ago. In this new work, bestselling Leadership Challenge authors Jim Kouzes and Barry Posner team up with experiential learning expert Elaine Biech to bring today's leaders over 100 engaging activities designed to expand and accelerate their leadership development efforts. Grounded in The Five Practices of Exemplary Leadership® model, The Leadership Challenge Activities Book in

  10. Eight challenges in phylodynamic inference

    Directory of Open Access Journals (Sweden)

    Simon D.W. Frost

    2015-03-01

    Full Text Available The field of phylodynamics, which attempts to enhance our understanding of infectious disease dynamics using pathogen phylogenies, has made great strides in the past decade. Basic epidemiological and evolutionary models are now well characterized with inferential frameworks in place. However, significant challenges remain in extending phylodynamic inference to more complex systems. These challenges include accounting for evolutionary complexities such as changing mutation rates, selection, reassortment, and recombination, as well as epidemiological complexities such as stochastic population dynamics, host population structure, and different patterns at the within-host and between-host scales. An additional challenge exists in making efficient inferences from an ever increasing corpus of sequence data.

  11. Grand Challenges facing Storage Systems

    CERN Document Server

    CERN. Geneva

    2004-01-01

    In this talk, we will discuss the future of storage systems. In particular, we will focus on several big challenges which we are facing in storage, such as being able to build, manage and backup really massive storage systems, being able to find information of interest, being able to do long-term archival of data, and so on. We also present ideas and research being done to address these challenges, and provide a perspective on how we expect these challenges to be resolved as we go forward.

  12. Nuclear energy: meeting the challenges

    International Nuclear Information System (INIS)

    'Nuclear Energy - Meeting the Challenges' was the theme of the 25th Annual Conference of the Canadian Nuclear Society, held in Toronto, Ontario on June 6-9, 2004. The theme has the implication of optimism - that we WILL meet the many challenges needed to overcome if nuclear power is to play a significant role in our energy future. The organizers succeeded in presenting a thorough discussion of the challenges facing the nuclear power industry in Canada with close to 300 delegates attending the three-day event

  13. Predicting missing links via correlation between nodes

    Science.gov (United States)

    Liao, Hao; Zeng, An; Zhang, Yi-Cheng

    2015-10-01

    As a fundamental problem in many different fields, link prediction aims to estimate the likelihood of an existing link between two nodes based on the observed information. Since this problem is related to many applications ranging from uncovering missing data to predicting the evolution of networks, link prediction has been intensively investigated recently and many methods have been proposed so far. The essential challenge of link prediction is to estimate the similarity between nodes. Most of the existing methods are based on the common neighbor index and its variants. In this paper, we propose to calculate the similarity between nodes by the Pearson correlation coefficient. This method is found to be very effective when applied to calculate similarity based on high order paths. We finally fuse the correlation-based method with the resource allocation method, and find that the combined method can substantially outperform the existing methods, especially in sparse networks.

  14. Predicting risky behavior in social communities

    CERN Document Server

    Simpson, Olivia

    2016-01-01

    Predicting risk profiles of individuals in networks (e.g.~susceptibility to a particular disease, or likelihood of smoking) is challenging for a variety of reasons. For one, `local' features (such as an individual's demographic information) may lack sufficient information to make informative predictions; this is especially problematic when predicting `risk,' as the relevant features may be precisely those that an individual is disinclined to reveal in a survey. Secondly, even if such features are available, they still may miss crucial information, as `risk' may be a function not just of an individual's features but also those of their friends and social communities. Here, we predict individual's risk profiles as a function of both their local features and those of their friends. Instead of modeling influence from the social network directly (which proved difficult as friendship links may be sparse and partially observed), we instead model influence by discovering social communities in the network that may be ...

  15. Optimal predictive model selection

    OpenAIRE

    Barbieri, Maria Maddalena; Berger, James O.

    2004-01-01

    Often the goal of model selection is to choose a model for future prediction, and it is natural to measure the accuracy of a future prediction by squared error loss. Under the Bayesian approach, it is commonly perceived that the optimal predictive model is the model with highest posterior probability, but this is not necessarily the case. In this paper we show that, for selection among normal linear models, the optimal predictive model is often the median probability model, which is defined a...

  16. Predictive software design measures

    OpenAIRE

    Love, Randall James

    1994-01-01

    This research develops a set of predictive measures enabling software testers and designers to identify and target potential problem areas for additional and/or enhanced testing. Predictions are available as early in the design process as requirements allocation and as late as code walk-throughs. These predictions are based on characteristics of the design artifacts prior to coding. Prediction equations are formed at established points in the software development process...

  17. Refugee status determination: three challenges

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  18. The Humpty-Dumpty Challenge.

    Science.gov (United States)

    Chock, Jan S.

    1995-01-01

    Describes a twist on the egg-drop challenge activity for an 8th grade physical science unit. Students engage in active inquiry and explore the laws of physics, develop critical thinking skills, and practice problem-solving tasks. (NB)

  19. Challenge of COPD: Getting Tested

    Science.gov (United States)

    ... please turn JavaScript on. Feature: The Challenge of COPD Getting Tested Past Issues / Fall 2014 Table of Contents Getting Tested Everyone at risk for COPD who has cough, sputum production, or shortness of ...

  20. Challenges in Designing Mechatronic Systems

    DEFF Research Database (Denmark)

    Torry-Smith, Jonas; Qamar, Ahsan; Achiche, Sofiane;

    2013-01-01

    Development of mechatronic products is traditionally carried out by several design experts from different design domains. Performing development of mechatronic products is thus greatly challenging. In order to tackle this, the critical challenges in mechatronics have to be well understood and well...... supported through applicable methods and tools. This paper aims at identifying the major challenges, by conducting a systematic and thorough survey of the most relevant research work in mechatronic design. Solutions proposed in literature are assessed and illustrated through a case study in order to...... investigate if the challenges can be handled appropriately by the methods, tools, and mindsets suggested by the mechatronic community. Using a real world mechatronics case, the paper identifies the areas where further research is required, by showing a clear connection between the actual problems faced during...

  1. The challenges of green nanotechnology

    Directory of Open Access Journals (Sweden)

    Miguel de la Guardia

    2014-03-01

    Full Text Available Nanomaterials have great impacts on life sciences; however,these advanced materials may induce inadvertant consequences.Thus, this editorial will highlight the futuristic challenges in green nanotechnology.

  2. Challenges in Soft Tissue Engineering

    OpenAIRE

    Yuksel, Eser; Choo, Joshua; Wettergreen, Matthew; Liebschner, Michael

    2005-01-01

    Soft tissue engineering strategies targeting restoration of volume loss have inherent critical challenges as they relate to the problem of restoration of defects with a high volume to surface ratio. We outline the problems associated with the limitations of translational applications regarding soft tissue engineering strategies as follows: cell survival, mechanical challenges: macroenvironment (scaffold collapse and on-the-shelf availability), compositional considerations: microenvironment, i...

  3. Challenges in Kurdish Text Processing

    OpenAIRE

    Esmaili, Kyumars Sheykh

    2012-01-01

    Despite having a large number of speakers, the Kurdish language is among the less-resourced languages. In this work we highlight the challenges and problems in providing the required tools and techniques for processing texts written in Kurdish. From a high-level perspective, the main challenges are: the inherent diversity of the language, standardization and segmentation issues, and the lack of language resources.

  4. Challenges to Nordic Police Research

    DEFF Research Database (Denmark)

    Holmberg, Lars

    2015-01-01

    The paper will cover three main points: A short description of published police research in the Nordic countries; a somewhat longer discussion of the nature of, and challenges to, Nordic police research and, finally, a critique of the homeliness of research.......The paper will cover three main points: A short description of published police research in the Nordic countries; a somewhat longer discussion of the nature of, and challenges to, Nordic police research and, finally, a critique of the homeliness of research....

  5. Challenges when introducing electronic exam

    OpenAIRE

    Kuikka, Matti; Kitola, Markus; Mikko-Jussi LAAKSO

    2014-01-01

    Time pressures often necessitate the use of more efficient exam tools, such as electronic exams (e-exams), instead of traditional paper exams. However, teachers may face challenges when introducing e-exams in a higher education context. This paper describes what kinds of challenges teachers may face when introducing e-exams, based on experiences in Turku University of Applied Sciences (TUAS) where e-exams have been used since 2012. For this research, the authors used their personal experience...

  6. Conclusion: challenges for the future

    OpenAIRE

    North, D. Warner

    1993-01-01

    The title “Challenges for the Future” implies the challenge to summarize a very complex meeting. Of necessity, I will present a personal impression. My interest is in risk assessment, which I define as a process for summarizing science in support of decision making. Risk assessment is sometimes regarded as arcane numerology, a rigid process of computing risk numbers in which much available science is unused. I am a strong advocate for the broader definition of risk assessment. It is encouragi...

  7. Internationalization challenges of Ethiopian SMEs

    OpenAIRE

    Yigzaw, Tamirat

    2014-01-01

    This study was made to find out what the internationalization challenges of Ethiopian small to medium size enterprises (SMEs) are. SMEs play a vital role in the economic development of a country. As the internationalization activities of these SMEs is affected by various factors, a research to identify the challenges that hinder their internationalization activities was made in order to minimize the internationalization problems faced in the future. A detailed literature review related to the...

  8. Testing earthquake predictions

    Science.gov (United States)

    Luen, Brad; Stark, Philip B.

    2008-01-01

    Statistical tests of earthquake predictions require a null hypothesis to model occasional chance successes. To define and quantify 'chance success' is knotty. Some null hypotheses ascribe chance to the Earth: Seismicity is modeled as random. The null distribution of the number of successful predictions - or any other test statistic - is taken to be its distribution when the fixed set of predictions is applied to random seismicity. Such tests tacitly assume that the predictions do not depend on the observed seismicity. Conditioning on the predictions in this way sets a low hurdle for statistical significance. Consider this scheme: When an earthquake of magnitude 5.5 or greater occurs anywhere in the world, predict that an earthquake at least as large will occur within 21 days and within an epicentral distance of 50 km. We apply this rule to the Harvard centroid-moment-tensor (CMT) catalog for 2000-2004 to generate a set of predictions. The null hypothesis is that earthquake times are exchangeable conditional on their magnitudes and locations and on the predictions - a common "nonparametric" assumption in the literature. We generate random seismicity by permuting the times of events in the CMT catalog. We consider an event successfully predicted only if (i) it is predicted and (ii) there is no larger event within 50 km in the previous 21 days. The P-value for the observed success rate is <0.001: The method successfully predicts about 5% of earthquakes, far better than 'chance' because the predictor exploits the clustering of earthquakes - occasional foreshocks - which the null hypothesis lacks. Rather than condition on the predictions and use a stochastic model for seismicity, it is preferable to treat the observed seismicity as fixed, and to compare the success rate of the predictions to the success rate of simple-minded predictions like those just described. If the proffered predictions do no better than a simple scheme, they have little value.

  9. MEMS performance challenges: packaging and shock tests

    Science.gov (United States)

    Chang, Jiyoung; Yang, Chen; Zhang, Bin; Lin, Liwei

    2011-06-01

    This paper describes recent advances in the MEMS performance challenges with emphases on packaging and shock tests. In the packaging area, metal to metal bonding processes have been developed to overcome limitations of the glass frit bonding by means of two specific methods: (1) pre-reflow of solder for enhanced bonding adhesion, and (2) the insertion of thin metal layer between parent metal bonding materials. In the shock test area, multiscale analysis for a MEMS package system has been developed with experimental verifications to investigate dynamic responses under drop-shock tests. Structural deformation and stress distribution data are extracted and predicted for device fracture and in-operation stiction analyses for micro mechanical components in various MEMS sensors, including accelerometers and gyroscopes.

  10. Facing Today's Exploration Challenges in the Gulf of Mexico

    Science.gov (United States)

    Detomo, R.

    2005-05-01

    The Gulf of Mexico represents one of the most intensively explored basins in the world, and yet it still delivers significant new material oil and gas discoveries every year. Because of it high productivity, geologic complexity, competitive acreage access and large profitability margins, the Gulf of Mexico presents many industry-leading challenges to Exploration today. For major companies exploring for oil and gas in the Gulf of Mexico today, their challenge is to "safely, responsibly and profitably find and produce reduced accumulations in increasingly hostile settings." The GoM serves as the sportsman's playground for a significant population located in and around its waters, and therefore, operating safely and responsibly are unassailable moral and operational standards by which we sustain future development, and maintain our license to operate. With that as a backdrop, today's challenges are driven by the nature of where the business is looking for new reserves in this extremely mature basin. These "Opportunities" encompass the following: 1) large, under-explored, sub-salt areas, characterized by poor seismic imaging, uncertain geologic regimes and potentially dangerous overpressures, 2) deep true-vertical-depth opportunities in older rocks that challenge our understanding of reservoir quality prediction and hydrocarbon systems, and are at the edge of today's drilling technologies, 3) access to sensitive areas including the eastern GoM-Florida shelf, coastal areas and international borders, 4) challenging "small accumulation" discoveries that cannot support expensive appraisal or development options, are remote to infrastructure or inefficiently produce the reservoir, and finally 5) new play development, which is challenged by long maturation cycles, small acreage blocks, intense international competition, and rapid lease rolls. This talk will consider what Shell and the Oil & Gas Industry does today to succeed in this arena, and specifically will show examples

  11. Predicting Predictable about Natural Catastrophic Extremes

    Science.gov (United States)

    Kossobokov, Vladimir

    2015-04-01

    By definition, an extreme event is rare one in a series of kindred phenomena. Usually (e.g. in Geophysics), it implies investigating a small sample of case-histories with a help of delicate statistical methods and data of different quality, collected in various conditions. Many extreme events are clustered (far from independent) and follow fractal or some other "strange" distribution (far from uniform). Evidently, such an "unusual" situation complicates search and definition of reliable precursory behaviors to be used for forecast/prediction purposes. Making forecast/prediction claims reliable and quantitatively probabilistic in the frames of the most popular objectivists' viewpoint on probability requires a long series of "yes/no" forecast/prediction outcomes, which cannot be obtained without an extended rigorous test of the candidate method. The set of errors ("success/failure" scores and space-time measure of alarms) and other information obtained in such a control test supplies us with data necessary to judge the candidate's potential as a forecast/prediction tool and, eventually, to find its improvements. This is to be done first in comparison against random guessing, which results confidence (measured in terms of statistical significance). Note that an application of the forecast/prediction tools could be very different in cases of different natural hazards, costs and benefits that determine risks, and, therefore, requires determination of different optimal strategies minimizing reliable estimates of realistic levels of accepted losses. In their turn case specific costs and benefits may suggest a modification of the forecast/prediction tools for a more adequate "optimal" application. Fortunately, the situation is not hopeless due to the state-of-the-art understanding of the complexity and non-linear dynamics of the Earth as a Physical System and pattern recognition approaches applied to available geophysical evidences, specifically, when intending to predict

  12. EVA Performance Prediction

    Science.gov (United States)

    Peacock, Brian; Maida, James; Rajulu, Sudhakar

    2004-01-01

    Astronaut physical performance capabilities in micro gravity EV A or on planetary surfaces when encumbered by a life support suit and debilitated by a long exposure to micro gravity will be less than unencumbered pre flight capabilities. The big question addressed by human factors engineers is: what can the astronaut be expected to do on EVA or when we arrive at a planetary surface? A second question is: what aids to performance will be needed to enhance the human physical capability? These questions are important for a number of reasons. First it is necessary to carry out accurate planning of human physical demands to ensure that time and energy critical tasks can be carried out with confidence. Second it is important that the crew members (and their ground or planetary base monitors) have a realistic picture of their own capabilities, as excessive fatigue can lead to catastrophic failure. Third it is important to design appropriate equipment to enhance human sensory capabilities, locomotion, materials handling and manipulation. The evidence from physiological research points to musculoskeletal, cardiovascular and neurovestibular degradation during long duration exposure to micro gravity . The evidence from the biomechanics laboratory (and the Neutral Buoyancy Laboratory) points to a reduction in range of motion, strength and stamina when encumbered by a pressurized suit. The evidence from a long history of EVAs is that crewmembers are indeed restricted in their physical capabilities. There is a wealth of evidence in the literature on the causes and effects of degraded human performance in the laboratory, in sports and athletics, in industry and in other physically demanding jobs. One approach to this challenge is through biomechanical and performance modeling. Such models must be based on thorough task analysis, reliable human performance data from controlled studies, and functional extrapolations validated in analog contexts. The task analyses currently carried

  13. A Molecular Dynamics Approach to Ligand-Receptor Interaction in the Aspirin-Human Serum Albumin Complex

    Directory of Open Access Journals (Sweden)

    H. Ariel Alvarez

    2012-01-01

    Full Text Available In this work, we present a study of the interaction between human serum albumin (HSA and acetylsalicylic acid (ASA, C9H8O4 by molecular dynamics simulations (MD. Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called “viscous work,” that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods.

  14. Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor ligand/receptor (PDGF/PDGFR) signaling.

    Science.gov (United States)

    Lamy, Sylvie; Beaulieu, Edith; Labbé, David; Bédard, Valérie; Moghrabi, Albert; Barrette, Stéphane; Gingras, Denis; Béliveau, Richard

    2008-05-01

    Most cancers are dependent on the growth of tumor blood vessels and inhibition of tumor angiogenesis may thus provide an efficient strategy to retard or block tumor growth. Recently, tumor vascular targeting has expanded to include not only endothelial cells (ECs) but also smooth muscle cells (SMCs), which contribute to a mature and functional vasculature. We have reported previously that delphinidin, a major biologically active constituent of berries, inhibits the vascular endothelial growth factor-induced phosphorylation of vascular endothelial growth factor receptor-2 and blocks angiogenesis in vitro and in vivo. In the present study, we show that delphinidin also inhibits activation of the platelet-derived growth factor (PDGF)-BB receptor-beta [platelet-derived growth factor receptor-beta (PDGFR-beta)] in SMC and that this inhibition may contribute to its antitumor effect. The inhibitory effect of delphinidin on PDGFR-beta was very rapid and led to the inhibition of PDGF-BB-induced activation of extracellular signal-regulated kinase (ERK)-1/2 signaling and of the chemotactic motility of SMC, as well as the differentiation and stabilization of EC and SMC into capillary-like tubular structures in a three-dimensional coculture system. Using an anthocyan-rich extract of berries, we show that berry extracts were able to suppress the synergistic induction of vessel formation by basic fibroblast growth factor-2 and PDGF-BB in the mouse Matrigel plug assay. Oral administration of the berry extract also significantly retarded tumor growth in a lung carcinoma xenograft model. Taken together, these results provide new insight into the molecular mechanisms underlying the antiangiogenic activity of delphinidin that will be helpful for the development of dietary-based chemopreventive strategies. PMID:18339683

  15. Optimization of Time-Resolved Fluorescence Assay for Detection of Eu-DOTA-labeled Ligand-Receptor Interactions

    OpenAIRE

    De Silva, Channa R.; Vagner, Josef; Lynch, Ronald; Gillies, Robert J.; Hruby, Victor J.

    2009-01-01

    Lanthanide-based luminescent ligand binding assays are superior to traditional radiolabel assays due to improved sensitivity and affordability in high throughput screening while eliminating the use of radioactivity. Despite significant progress using lanthanide(III)-coordinated chelators such as DTPA derivatives, dissociation-enhanced lanthanide fluoroimmunoassays (DELFIA) have not yet been successfully used with more stable chelators, e.g. DOTA derivatives, due to the incomplete release of l...

  16. Feedbacks, Receptor Clustering, and Receptor Restriction to Single Cells yield large Turing Spaces for Ligand-receptor based Turing Models

    OpenAIRE

    Kurics, Tamás; Menshykau, Denis; Iber, Dagmar

    2014-01-01

    Turing mechanisms can yield a large variety of patterns from noisy, homogenous initial conditions and have been proposed as patterning mechanism for many developmental processes. However, the molecular components that give rise to Turing patterns have remained elusive, and the small size of the parameter space that permits Turing patterns to emerge makes it difficult to explain how Turing patterns could evolve. We have recently shown that Turing patterns can be obtained with a single ligand i...

  17. Optimization of time-resolved fluorescence assay for detection of europium-tetraazacyclododecyltetraacetic acid-labeled ligand-receptor interactions.

    Science.gov (United States)

    De Silva, Channa R; Vagner, Josef; Lynch, Ronald; Gillies, Robert J; Hruby, Victor J

    2010-03-01

    Lanthanide-based luminescent ligand binding assays are superior to traditional radiolabel assays due to improving sensitivity and affordability in high-throughput screening while eliminating the use of radioactivity. Despite significant progress using lanthanide(III)-coordinated chelators such as diethylenetriaminepentaacetic acid (DTPA) derivatives, dissociation-enhanced lanthanide fluoroimmunoassays (DELFIAs) have not yet been successfully used with more stable chelators (e.g., tetraazacyclododecyltetraacetic acid [DOTA] derivatives) due to the incomplete release of lanthanide(III) ions from the complex. Here a modified and optimized DELFIA procedure incorporating an acid treatment protocol is introduced for use with Eu(III)-DOTA-labeled peptides. Complete release of Eu(III) ions from DOTA-labeled ligands was observed using hydrochloric acid (2.0M) prior to the luminescent enhancement step. [Nle(4),d-Phe(7)]-alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) labeled with Eu(III)-DOTA was synthesized, and the binding affinity to cells overexpressing the human melanocortin-4 (hMC4) receptor was evaluated using the modified protocol. Binding data indicate that the Eu(III)-DOTA-linked peptide bound to these cells with an affinity similar to its DTPA analogue. The modified DELFIA procedure was further used to monitor the binding of an Eu(III)-DOTA-labeled heterobivalent peptide to the cells expressing both hMC4 and cholecystokinin-2 (CCK-2) receptors. The modified assay provides superior results and is appropriate for high-throughput screening of ligand libraries. PMID:19852924

  18. ENTHALPY-ENTROPY COMPENSATION AND COOPERATIVITY AS THERMODYNAMIC EPIPHENOMENA OF STRUCTURAL FLEXIBILITY IN LIGAND-RECEPTOR INTERACTIONS

    OpenAIRE

    Ferrante, Andrea; Gorski, Jack

    2012-01-01

    Ligand binding is a thermodynamically cooperative process in many biochemical systems characterized by the conformational flexibility of the reactants. However the contribution of conformational entropy to cooperativity of ligation needs to be elucidated. Here we perform kinetic and thermodynamic analyses on a panel of cycle-mutated peptides, derived from influenza H3 HA306-319, interacting with wild type and a mutant HLA-DR. We observe that within a certain range of peptide affinity, this sy...

  19. Numerical prediction of slamming loads

    DEFF Research Database (Denmark)

    Seng, Sopheak; Jensen, Jørgen J; Pedersen, Preben T

    2012-01-01

    calculations in a realistic wave environment.Both the global and the local slamming loads are assessed numerically using a finite-volume formulation with the free surface captured by a volume-of-fluid technique. This numerical procedure is justified by comprehensive validation studies where numerically......It is important to include the contribution of the slamming-induced response in the structural design of large vessels with a significant bow flare. At the same time it is a challenge to develop rational tools to determine the slamming-induced loads and the prediction of their occurrence. Today it...... is normal practice to apply a standard sea-keeping procedure to determine the relative velocity distribution between the water surface and the hull and then to estimate the bottom slamming loads and the bow-flare slamming loads based on two-dimensional formulations similarly to water-entry problems...

  20. Academic Training: Predicting Natural Catastrophes

    CERN Multimedia

    Françoise Benz

    2005-01-01

    2005-2006 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 12, 13, 14, 15, 16 December from 11:00 to 12:00 - Main Auditorium, bldg. 500 Predicting Natural Catastrophes E. OKAL / Northwestern University, Evanston, USA 1. Tsunamis -- Introduction Definition of phenomenon - basic properties of the waves Propagation and dispersion Interaction with coasts - Geological and societal effects Origin of tsunamis - natural sources Scientific activities in connection with tsunamis. Ideas about simulations 2. Tsunami generation The earthquake source - conventional theory The earthquake source - normal mode theory The landslide source Near-field observation - The Plafker index Far-field observation - Directivity 3. Tsunami warning General ideas - History of efforts Mantle magnitudes and TREMOR algorithms The challenge of 'tsunami earthquakes' Energy-moment ratios and slow earthquakes Implementation and the components of warning centers 4. Tsunami surveys Principles and methodologies Fifteen years of field surveys and re...

  1. Prediction of protein subunits using KEGG BRITE

    OpenAIRE

    Dias, Oscar; Liu, Filipe; Rocha, Miguel; Ferreira, E.C.; Rocha, I

    2014-01-01

    The increased importance of genome-scale metabolic models (GSMMs) within systems biology and metabolic engineering, led to the development of several computational frameworks dedicated to their reconstruction. One of the toughest challenges, when reconstructing a model is associated to the identification of gene-protein-reaction (GPR) associations, a step usually performed by manually searching literature. In this work, we present a new approach for automatically predicting, at the genome lev...

  2. Mining Big Data to Predicting Future

    OpenAIRE

    Tyagi, Amit K.; Priya, R.

    2015-01-01

    Due to technological advances, vast data sets (e.g. big data) are increasing now days. Big Data a new term; is used to identify the collected datasets. But due to their large size and complexity, we cannot manage with our current methodologies or data mining software tools to extract those datasets. Such datasets provide us with unparalleled opportunities for modelling and predicting of future with new challenges. So as an awareness of this and weaknesses as well as the possibilit...

  3. Model Predictive Control of Autonomous Vehicles

    OpenAIRE

    Zanon, Mario; Frasch, Janick V.; Vukov, Milan; Sager, Sebastian; Diehl, Moritz

    2014-01-01

    International audience The control of autonomous vehicles is a challenging task that requires advanced control schemes. Nonlinear Model Predictive Control (NMPC) and Moving Horizon Estimation (MHE) are optimization-based control and estimation techniques that are able to deal with highly nonlinear, constrained, unstable and fast dynamic systems. In this chapter, these techniques are detailed, a descriptive nonlinear model is derived and the performance of the proposed control scheme is dem...

  4. Phenotype prediction in regulated metabolic networks

    OpenAIRE

    Centler Florian; Kaleta Christoph; di Fenizio Pietro; Dittrich Peter

    2008-01-01

    Abstract Background Due to the growing amount of biological knowledge that is incorporated into metabolic network models, their analysis has become more and more challenging. Here, we examine the capabilities of the recently introduced chemical organization theory (OT) to ease this task. Considering only network stoichiometry, the theory allows the prediction of all potentially persistent species sets and therewith rigorously relates the structure of a network to its potential dynamics. By th...

  5. Current Methods for Predicting Human Food Effect

    OpenAIRE

    Lentz, Kimberley A.

    2008-01-01

    Food can impact the pharmacokinetics of a drug product through several mechanisms, including but not limited to, enhancement in drug solubility, changes in GI physiology, or direct interaction with the drug. Significant food effects complicate development of new drugs, especially when clinical plans require control and/or monitoring of food intake in relation to dosing. The prediction of whether a drug or drug product will show a human food effect is challenging. In vitro models which conside...

  6. Predictive access control for distributed computation

    DEFF Research Database (Denmark)

    Yang, Fan; Hankin, Chris; Nielson, Flemming;

    2013-01-01

    We show how to use aspect-oriented programming to separate security and trust issues from the logical design of mobile, distributed systems. The main challenge is how to enforce various types of security policies, in particular predictive access control policies — policies based on the future...... behavior of a program. A novel feature of our approach is that we can define policies concerning secondary use of data....

  7. The Mock LISA Data Challenges: from Challenge 1B to Challenge 3

    International Nuclear Information System (INIS)

    The Mock LISA Data Challenges are a programme to demonstrate and encourage the development of LISA data-analysis capabilities, tools and techniques. At the time of this workshop, three rounds of challenges had been completed, and the next was about to start. In this paper we provide a critical analysis of the entries to the latest completed round, Challenge 1B. The entries confirm the consolidation of a range of data-analysis techniques for galactic and massive-black-hole binaries, and they include the first convincing examples of detection and parameter estimation of extreme-mass-ratio inspiral sources. In this paper we also introduce the next round, Challenge 3. Its data sets feature more realistic waveform models (e.g., galactic binaries may now chirp, and massive-black-hole binaries may precess due to spin interactions), as well as new source classes (bursts from cosmic strings, isotropic stochastic backgrounds) and more complicated nonsymmetric instrument noise

  8. The Mock LISA Data Challenges: from Challenge 1B to Challenge 3

    CERN Document Server

    Babak, Stanislav; Benacquista, Matthew J; Cornish, Neil J; Crowder, Jeff; Larson, Shane L; Plagnol, Eric; Porter, Edward K; Vallisneri, Michele; Vecchio, Alberto; Arnaud, Keith; Barack, Leor; Błaut, Arkadiusz; Cutler, Curt; Fairhurst, Stephen; Gair, Jonathan; Gong, Xuefei; Harry, Ian; Khurana, Deepak; Królak, Andrzej; Mandel, Ilya; Prix, Reinhard; Sathyaprakash, B S; Savov, Pavlin; Shang, Yu; Trias, Miquel; Veitch, John; Wang, Yan; Wen, Linqing; Whelan, John T

    2008-01-01

    The Mock LISA Data Challenges are a programme to demonstrate and encourage the development of LISA data-analysis capabilities, tools and techniques. At the time of this workshop, three rounds of challenges had been completed, and the next was about to start. In this article we provide a critical analysis of entries to the latest completed round, Challenge 1B. The entries confirm the consolidation of a range of data-analysis techniques for Galactic and massive--black-hole binaries, and they include the first convincing examples of detection and parameter estimation of extreme--mass-ratio inspiral sources. In this article we also introduce the next round, Challenge 3. Its data sets feature more realistic waveform models (e.g., Galactic binaries may now chirp, and massive--black-hole binaries may precess due to spin interactions), as well as new source classes (bursts from cosmic strings, isotropic stochastic backgrounds) and more complicated nonsymmetric instrument noise.

  9. IMPLANT REMOVAL: AN UNSOLVED CHALLENGE TO ORTHOPAEDICIAN

    Directory of Open Access Journals (Sweden)

    Varunjikar

    2014-04-01

    Full Text Available Its general consciences amongst the Orthopaedicians, that Implant removal is a challenging one. Newer generation is not aware of implants used in the past & if there is any patient where its removal is indicated it becomes a challenge. Unavailability of necessary & proper instruments as extractor or hook makes the task difficult. Surgeon has to rely on his mechanical skill, modification in procedure, and way of thinking in tackling the situation in present scenario with whatever things are there on trolley & in the armamentarium. We are presenting a case of intramedullary tibial implant – two V nails, put about 8 years ago having pain &sinus in upper third of leg. It was difficult to predict radiologically the nature of the intra- medullary implant & hence, difficulties during its removal. It is mandatory to discuss all the possible options with the patient and relatives prior to surgery. It is also necessary to explain at times, we might not be able to remove the implant and procedure have to be abandoned. The patient usually considers the removal of implant to be easier than the initial surgery and is usually unaware of the difficulties that can be encountered during removal and the fact that it may need a major procedure followed by a prolonged recovery time.

  10. Ocean OSSEs: recent developments and future challenges

    Science.gov (United States)

    Kourafalou, V. H.

    2012-12-01

    Atmospheric OSSEs have had a much longer history of applications than OSSEs (and OSEs) in oceanography. Long standing challenges include the presence of coastlines and steep bathymetric changes, which require the superposition of a wide variety of space and time scales, leading to difficulties on ocean observation and prediction. For instance, remote sensing is critical for providing a quasi-synoptic oceanographic view, but the coverage is limited at the ocean surface. Conversely, in situ measurements are capable to monitor the entire water column, but at a single location and usually for a specific, short time. Despite these challenges, substantial progress has been made in recent years and international initiatives have provided successful OSSE/OSE examples and formed appropriate forums that helped define the future roadmap. These will be discussed, together with various challenges that require a community effort. Examples include: integrated (remote and in situ) observing system requirements for monitoring large scale and climatic changes, vs. short term variability that is particularly important on the regional and coastal spatial scales; satisfying the needs of both global and regional/coastal nature runs, from development to rigorous evaluation and under a clear definition of metrics; data assimilation in the presence of tides; estimation of real-time river discharges for Earth system modeling. An overview of oceanographic efforts that complement the standard OSSE methodology will also be given. These include ocean array design methods, such as representer-based analysis and adaptive sampling. Exciting new opportunities for both global and regional ocean OSSE/OSE studies have recently become possible with targeted periods of comprehensive data sets, such as the existing Gulf of Mexico observations from multiple sources in the aftermath of the DeepWater Horizon incident and the upcoming airborne AirSWOT, in preparation for the SWOT (Surface Water and Ocean

  11. Stable isotope views on ecosystem function: challenging or challenged?

    Science.gov (United States)

    Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

    2010-01-01

    Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

  12. Predictable or not predictable? The MOV question

    International Nuclear Information System (INIS)

    Over the past 8 years, the nuclear industry has struggled to understand the dynamic phenomena experienced during motor-operated valve (MOV) operation under differing flow conditions. For some valves and designs, their operational functionality has been found to be predictable; for others, unpredictable. Although much has been accomplished over this period of time, especially on modeling valve dynamics, the unpredictability of many valves and designs still exists. A few valve manufacturers are focusing on improving design and fabrication techniques to enhance product reliability and predictability. However, this approach does not address these issues for installed and inpredictable valves. This paper presents some of the more promising techniques that Wyle Laboratories has explored with potential for transforming unpredictable valves to predictable valves and for retrofitting installed MOVs. These techniques include optimized valve tolerancing, surrogated material evaluation, and enhanced surface treatments

  13. Challenges and counter challenges in HIV/AIDS

    Institute of Scientific and Technical Information of China (English)

    Qingsheng Li; Charles Wood

    2010-01-01

    @@ Since the beginning of the HIV/AIDS pandemic, there has been significant progress in combating the virus.In addition to identifying HIV,1 scientists have developed an array of antiretroviral drugs and successfully converted the once deadly disease into a treatable and chronic condition.2 Nevertheless, this battle is far from over and HIV still outsmarts humans in multiple ways and poses tremendous challenges. Within this context, the Chinese Medical Journal has timely published this special issue on HIV/AIDS, highlighting the ongoing challenges posed by HIV and potential solutions to these problems.

  14. Data Mining and Neural Network Techniques in Stock Market Prediction : A Methodological Review

    Directory of Open Access Journals (Sweden)

    Debashish Das

    2013-02-01

    Full Text Available Prediction in any field is a complicated, challenging and daunting process. Employing traditional methodsmay not ensure the reliability of the prediction. In this paper, we are reviewing the possibility of applyingtwo well-known techniques neural network and data mining in stock market prediction. As neural networkis able to extract useful information from a huge data set and data mining is also able to predict futuretrends and behaviors. Therefore, a combination of both these techniques could make the prediction muchreliable.

  15. ITER safety challenges and opportunities

    International Nuclear Information System (INIS)

    This paper reports on results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ITER is capable of meeting anticipated regulatory dose limits, but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. Much research and development (R ampersand D) and design analysis is needed to establish that ITER meets regulatory requirements. There is a further oportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, three programmatic challenges and three technical challenges must be overcome. The first step is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of three key technical challenges is plasma engineering - burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost

  16. Ecological Challenges for Closed Systems

    Science.gov (United States)

    Nelson, Mark; Dempster, William; Allen, John P.

    2012-07-01

    Closed ecological systems are desirable for a number of purposes. In space life support systems, material closure allows precious life-supporting resources to be kept inside and recycled. Closure in small biospheric systems facilitates detailed measurement of global ecological processes and biogeochemical cycles. Closed testbeds facilitate research topics which require isolation from the outside (e.g. genetically modified organisms; radioisotopes) so their ecological interactions and fluxes can be studied separate from interactions with the outside environment. But to achieve and maintain closure entails solving complex ecological challenges. These challenges include being able to handle faster cycling rates and accentuated daily and seasonal fluxes of critical life elements such as carbon dioxide, oxygen, water, macro- and mico-nutrients. The problems of achieving sustainability in closed systems for life support include how to handle atmospheric dynamics including trace gases, producing a complete human diet and recycling nutrients and maintaining soil fertility, the sustaining of healthy air and water and preventing the loss of crucial elements from active circulation. In biospheric facilities the challenge is also to produce analogues to natural biomes and ecosystems, studying processes of self-organization and adaptation in systems that allow specification or determination of state variables and cycles which may be followed through all interactions from atmosphere to soils. Other challenges include the dynamics and genetics of small populations, the psychological challenges for small isolated human groups and measures and options which may be necessary to ensure long-term operation of closed ecological systems.

  17. Rising to the challenge: Deep acting is more beneficial when tasks are appraised as challenging.

    Science.gov (United States)

    Huang, Jason L; Chiaburu, Dan S; Zhang, Xin-an; Li, Ning; Grandey, Alicia A

    2015-09-01

    Cumulative research indicates that deep acting has a nonsignificant relationship with employee exhaustion, despite arguments that deep acting can be beneficial. To illuminate when deep acting leads to more positive employee outcomes, we draw on the resource conservation perspective to propose a within-individual model of deep acting that focuses on service employees' daily fluctuation of emotional labor and emotional exhaustion. Specifically, we propose that the ongoing experience of felt challenge is a within-person boundary condition that moderates deep acting's relationship with emotional exhaustion, and model emotional exhaustion as a mediating mechanism that subsequently predicts momentary job satisfaction and daily customer conflict handling. Using an experience sampling design, we collected data from 84 service employees over a 3-week period. Deep acting was less emotionally exhausting for service providers when they saw their tasks as more challenging. Furthermore, emotional exhaustion mediated the deep acting by felt challenge interaction effect on momentary job satisfaction and daily customer conflict handling. The findings contribute to a better understanding of the deep acting experience at work, while highlighting customer conflict handling as a key behavioral outcome of emotional labor. PMID:25751748

  18. A systems biology approach to transcription factor binding site prediction.

    Directory of Open Access Journals (Sweden)

    Xiang Zhou

    Full Text Available BACKGROUND: The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates. METHODOLOGY/PRINCIPAL FINDINGS: We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data. CONCLUSIONS/SIGNIFICANCE: Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct

  19. Chemoinformatics: Achievements and Challenges, a Personal View

    Directory of Open Access Journals (Sweden)

    Johann Gasteiger

    2016-01-01

    Full Text Available Chemoinformatics provides computer methods for learning from chemical data and for modeling tasks a chemist is facing. The field has evolved in the past 50 years and has substantially shaped how chemical research is performed by providing access to chemical information on a scale unattainable by traditional methods. Many physical, chemical and biological data have been predicted from structural data. For the early phases of drug design, methods have been developed that are used in all major pharmaceutical companies. However, all domains of chemistry can benefit from chemoinformatics methods; many areas that are not yet well developed, but could substantially gain from the use of chemoinformatics methods. The quality of data is of crucial importance for successful results. Computer-assisted structure elucidation and computer-assisted synthesis design have been attempted in the early years of chemoinformatics. Because of the importance of these fields to the chemist, new approaches should be made with better hardware and software techniques. Society’s concern about the impact of chemicals on human health and the environment could be met by the development of methods for toxicity prediction and risk assessment. In conjunction with bioinformatics, our understanding of the events in living organisms could be deepened and, thus, novel strategies for curing diseases developed. With so many challenging tasks awaiting solutions, the future is bright for chemoinformatics.

  20. Chemoinformatics: Achievements and Challenges, a Personal View.

    Science.gov (United States)

    Gasteiger, Johann

    2016-01-01

    Chemoinformatics provides computer methods for learning from chemical data and for modeling tasks a chemist is facing. The field has evolved in the past 50 years and has substantially shaped how chemical research is performed by providing access to chemical information on a scale unattainable by traditional methods. Many physical, chemical and biological data have been predicted from structural data. For the early phases of drug design, methods have been developed that are used in all major pharmaceutical companies. However, all domains of chemistry can benefit from chemoinformatics methods; many areas that are not yet well developed, but could substantially gain from the use of chemoinformatics methods. The quality of data is of crucial importance for successful results. Computer-assisted structure elucidation and computer-assisted synthesis design have been attempted in the early years of chemoinformatics. Because of the importance of these fields to the chemist, new approaches should be made with better hardware and software techniques. Society's concern about the impact of chemicals on human health and the environment could be met by the development of methods for toxicity prediction and risk assessment. In conjunction with bioinformatics, our understanding of the events in living organisms could be deepened and, thus, novel strategies for curing diseases developed. With so many challenging tasks awaiting solutions, the future is bright for chemoinformatics. PMID:26828468

  1. The Challenges of Becoming Agile

    DEFF Research Database (Denmark)

    Ovesen, Nis

    use of a radically different and empirically based process control model originating from the domain of software development, namely the process framework called Scrum. Scrum as a process framework is often identified with the overall development paradigm coined as Agile Development and during the...... last decade it has gained a vast success in software development due to its lightweight character and efficient way of handling the challenges of increased market speed, change and product complexity. Now, traditional product development companies are beginning to discover the Scrum framework as a...... potential solution to their struggles with similar challenges. This Ph.D. project is based on case studies of the development environments of seven Danish companies working with the implementation of Scrum. The outcome of the project is an identification and overview of the challenges of implementing and...

  2. The Challenges of Becoming Agile

    DEFF Research Database (Denmark)

    Ovesen, Nis; Dowlen, Chris

    2012-01-01

    During the last decade agile methods have been a vast success in the domain of software development. This paper investigates whether these methods can be successfully transferred to the domain of physical product development in order to address the fundamental challenges of increased marked speed......, development uncertainty and product complexity. The paper compares two cases from industry and education where agile methods are used in physical product development. The comparison between the cases is conducted within five thematic areas, which creates an overview of the challenges that may occur when...... implementing agile methods. The present paper is concluded by a discussion and conclusion drawing up the main challenges experienced and well as the benefits of utilising agile methods in physical product development....

  3. Challenges in future linear colliders

    CERN Document Server

    Chattopadhyay, S

    2002-01-01

    For decades, electron-positron colliders have been complementing proton-proton colliders. But the circular LEP, the largest e/sup -/e /sup +/ collider, represented an energy limit beyond which energy losses to synchrotron radiation necessitate moving to e/sup -/e/sup + / linear colliders (LCs), thereby raising new challenges for accelerator builders. Japanese-American, German, and European collaborations have presented options for the "Future Linear Collider " (FLC). Key accelerator issues for any FLC option are the achievement of high enough energy and luminosity. Damping rings, taking advantage of the phenomenon of synchrotron radiation, have been developed as the means for decreasing beam size, which is crucial for ensuring a sufficiently high rate of particle-particle collisions. Related challenges are alignment and stability in an environment where even minute ground motion can disrupt performance, and the ability to monitor beam size. The technical challenges exist within a wider context of socioeconomi...

  4. Higgs Machine Learning Challenge 2014

    CERN Multimedia

    Olivier, A-P; Bourdarios, C ; LAL / Orsay; Goldfarb, S ; University of Michigan

    2014-01-01

    High Energy Physics (HEP) has been using Machine Learning (ML) techniques such as boosted decision trees (paper) and neural nets since the 90s. These techniques are now routinely used for difficult tasks such as the Higgs boson search. Nevertheless, formal connections between the two research fields are rather scarce, with some exceptions such as the AppStat group at LAL, founded in 2006. In collaboration with INRIA, AppStat promotes interdisciplinary research on machine learning, computational statistics, and high-energy particle and astroparticle physics. We are now exploring new ways to improve the cross-fertilization of the two fields by setting up a data challenge, following the footsteps of, among others, the astrophysics community (dark matter and galaxy zoo challenges) and neurobiology (connectomics and decoding the human brain). The organization committee consists of ATLAS physicists and machine learning researchers. The Challenge will run from Monday 12th to September 2014.

  5. Einstein's Theory Fights off Challengers

    Science.gov (United States)

    2010-04-01

    Two new and independent studies have put Einstein's General Theory of Relativity to the test like never before. These results, made using NASA's Chandra X-ray Observatory, show Einstein's theory is still the best game in town. Each team of scientists took advantage of extensive Chandra observations of galaxy clusters, the largest objects in the Universe bound together by gravity. One result undercuts a rival gravity model to General Relativity, while the other shows that Einstein's theory works over a vast range of times and distances across the cosmos. The first finding significantly weakens a competitor to General Relativity known as "f(R) gravity". "If General Relativity were the heavyweight boxing champion, this other theory was hoping to be the upstart contender," said Fabian Schmidt of the California Institute of Technology in Pasadena, who led the study. "Our work shows that the chances of its upsetting the champ are very slim." In recent years, physicists have turned their attention to competing theories to General Relativity as a possible explanation for the accelerated expansion of the universe. Currently, the most popular explanation for the acceleration is the so-called cosmological constant, which can be understood as energy that exists in empty space. This energy is referred to as dark energy to emphasize that it cannot be directly detected. In the f(R) theory, the cosmic acceleration comes not from an exotic form of energy but from a modification of the gravitational force. The modified force also affects the rate at which small enhancements of matter can grow over the eons to become massive clusters of galaxies, opening up the possibility of a sensitive test of the theory. Schmidt and colleagues used mass estimates of 49 galaxy clusters in the local universe from Chandra observations, and compared them with theoretical model predictions and studies of supernovas, the cosmic microwave background, and the large-scale distribution of galaxies. They

  6. The Challenge of Prejudice: Counsellors' Talk about Challenging Clients' Prejudices

    Science.gov (United States)

    Spong, Sheila J.

    2012-01-01

    This paper considers the implications for training and practice of counsellors' responses to the notion of challenging clients' prejudices. It explores tensions in counselling discourse between social responsibility, responsibility to the client and responsibility for one's self as counsellor. Three focus groups of counsellors were asked whether a…

  7. Success of Breast Cancer Startup Challenge Inspires Second Challenge | Poster

    Science.gov (United States)

    By Thomas Stackhouse, Joseph Conrad, and Michele Newton, Contributing Writers, and Rosemarie Truman, Guest Writer Sixty-one teams have been accepted into, and are now competing in, the Neuro Startup Challenge, a new collaboration established by the National Institutes of Health (NIH) with The Center for Advancing Innovation (CAI) and Heritage Provider Network, Inc.

  8. Challenged

    Science.gov (United States)

    Manzo, Kathleen Kennedy

    2006-01-01

    The work of librarians can be a lifeline to youths dealing with difficult personal issues, such as family strife, growing up, and sexuality. This paper presents an issue where school library books at Fayetteville High School are questioned because their books are too sexually explicit or mature for teenagers. In the midst of intense media coverage…

  9. ITER safety challenges and opportunities

    International Nuclear Information System (INIS)

    Results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ''ITER is capable of meeting anticipated regulatory dose limits,'' but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. We need much research and development (R ampersand D) and design analysis to establish that ITER meets regulatory requirements. We have a further opportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, we need to overcome three programmatic challenges and three technical challenges. The first programmatic challenge is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of the three key technical challenges is plasma engineering -- burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost. Some design requirements are now too strict; some are too lax. Fuel cycle design requirements are presently too strict, mandating inappropriate T separation from H and D. Heat sink requirements are presently too lax; they should be strengthened to ensure that maximum loss of coolant accident temperatures drop

  10. Fired up or burned out? How developmental challenge differentially impacts leader behavior.

    Science.gov (United States)

    Courtright, Stephen H; Colbert, Amy E; Choi, Daejeong

    2014-07-01

    Leadership development research has largely drawn on experiential and enactive learning theories to explore the positive effects of developmental challenge on leaders. In contrast, we examined potential positive and negative effects of developmental challenge (i.e., challenging job assignments) on leader behavior through an alternative theoretical lens--transactional stress theory. We predicted, on one hand, that developmental challenge may be associated with higher leader engagement and transformational leadership behavior; however, developmental challenge also has the potential to be associated with higher leader emotional exhaustion and laissez-faire leadership behavior. We further proposed that leadership self-efficacy (LSE) moderates these potential effects of developmental challenge and helps explain why leaders react either positively or negatively to developmental challenge. We tested our hypotheses in a sample of 153 leaders and 631 direct reports at a Fortune 500 company. Findings supported positive relationships among developmental challenge, leader engagement, and transformational leadership. However, we also found support for significant relationships among developmental challenge, emotional exhaustion, and laissez-faire leadership. Additionally, leaders lower in LSE were more likely to encounter the negative effects of developmental challenge by experiencing increased emotional exhaustion and displaying laissez-faire leadership behaviors. Our study contributes to theory and practice by elucidating a "dark side" of developmental challenge, identifying LSE as a moderator of the negative effects of developmental challenge, identifying antecedents of transformational and laissez-faire leadership behaviors, and investigating demands and stress in leadership roles. PMID:24490967

  11. Visualizing Risk Prediction Models

    OpenAIRE

    Vanya Van Belle; Ben Van Calster

    2015-01-01

    Objective Risk prediction models can assist clinicians in making decisions. To boost the uptake of these models in clinical practice, it is important that end-users understand how the model works and can efficiently communicate its results. We introduce novel methods for interpretable model visualization. Methods The proposed visualization techniques are applied to two prediction models from the Framingham Heart Study for the prediction of intermittent claudication and stroke after atrial fib...

  12. Pyroshock prediction procedures

    Science.gov (United States)

    Piersol, Allan G.

    2002-05-01

    Given sufficient effort, pyroshock loads can be predicted by direct analytical procedures using Hydrocodes that analytically model the details of the pyrotechnic explosion and its interaction with adjacent structures, including nonlinear effects. However, it is more common to predict pyroshock environments using empirical procedures based upon extensive studies of past pyroshock data. Various empirical pyroshock prediction procedures are discussed, including those developed by the Jet Propulsion Laboratory, Lockheed-Martin, and Boeing.

  13. Predicting transformers oil parameters

    OpenAIRE

    Shaban, K.; El-Hag, A.; Matveev, A.

    2009-01-01

    In this paper different configurations of artificial neural networks are applied to predict various transformers oil parameters. The prediction is performed through modeling the relationship between the transformer insulation resistance extracted from the Megger test and the breakdown strength, interfacial tension, acidity and the water content of the transformers oil. The process of predicting these oil parameters statuses is carried out using two different configurations of neural networks....

  14. Is Suicide Predictable?

    OpenAIRE

    Asmaee, S; Mosavi, N; R Abdul Rashid; H Habi; Seghatoleslam, T; Naseri, A.

    2012-01-01

    Background: The current study aimed to test the hypothesis: Is suicide predictable? And try to classify the predictive factors in multiple suicide attempts. Methods: A cross-sectional study was administered to 223 multiple attempters, women who came to a medical poison centre after a suicide attempt. The participants were young, poor, and single. A Logistic Regression Analiysis was used to classify the predictive factors of suicide. Results: Women who had multiple suicide attempts exhibited a...

  15. Statistical Challenges in Modern Astronomy

    CERN Document Server

    Feigelson, E D

    2003-01-01

    Despite centuries of close association, statistics and astronomy are surprisingly distant today. Most observational astronomical research relies on an inadequate toolbox of methodological tools. Yet the needs are substantial: astronomy encounters sophisticated problems involving sampling theory, survival analysis, multivariate classification and analysis, time series analysis, wavelet analysis, spatial point processes, nonlinear regression, bootstrap resampling and model selection. We review the recent resurgence of astrostatistical research, and outline new challenges raised by the emerging Virtual Observatory. Our essay ends with a list of research challenges and infrastructure for astrostatistics in the coming decade.

  16. The challenges of big data.

    Science.gov (United States)

    Mardis, Elaine R

    2016-05-01

    The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  17. Grand Challenges of Enterprise Integration

    Energy Technology Data Exchange (ETDEWEB)

    Brosey, W.D; Neal, R.E.; Marks, D.

    2001-04-01

    Enterprise Integration connects and combines people, processes, systems, and technologies to ensure that the right people and the right processes have the right information and the right resources at the right time. A consensus roadmap for Technologies for Enterprise Integration was created as part of an industry/government/academia partnership in the Integrated Manufacturing Technology Initiative (IMTI). Two of the grand challenges identified by the roadmapping effort will be addressed here--Customer Responsive Enterprises and Totally Connected Enterprises. Each of these challenges is briefly discussed as to the current state of industry and the future vision as developed in the roadmap.

  18. The challenges of big data

    Science.gov (United States)

    2016-01-01

    ABSTRACT The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  19. The Challenges of Credible Thermal Protection System Reliability Quantification

    Science.gov (United States)

    Green, Lawrence L.

    2013-01-01

    The paper discusses several of the challenges associated with developing a credible reliability estimate for a human-rated crew capsule thermal protection system. The process of developing such a credible estimate is subject to the quantification, modeling and propagation of numerous uncertainties within a probabilistic analysis. The development of specific investment recommendations, to improve the reliability prediction, among various potential testing and programmatic options is then accomplished through Bayesian analysis.

  20. Internet anonymity with mobility - key challenges for the future.

    OpenAIRE

    Doswell, Stephen

    2013-01-01

    Privacy, including the privacy of correspondence (communications), is a human right. Privacy Enhancing Technologies (PETs) provide a number of tools with the aim to protect this right. Anonymity networks, such as Tor, contribute to privacy by providing a degree of anonymity for an individual's Internet traffic. An increase in mobile devices connecting to the Internet is predicted to surpass static connections by 2014. The desire for privacy will provide additional challenges in the future, fo...

  1. Organotypic liver culture models: Meeting current challenges in toxicity testing

    OpenAIRE

    LeCluyse, Edward L.; Witek, Rafal P; Andersen, Melvin E.; Powers, Mark J.

    2012-01-01

    Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive respo...

  2. Interference Alignment: Practical Challenges and Test-bed Implementation

    OpenAIRE

    Moghadam, Nima N.; Farhadi, Hamed; Zetterberg, Per; Khormuji, Majid Nasiri; Skoglund, Mikael

    2014-01-01

    Data traffic over wireless communication networks has experienced a tremendous growth in the last decade, and it is predicted to exponentially increase in the next decades. Enabling future wireless networks to fulfill this expectation is a challenging task both due to the scarcity of radio resources (e.g. spectrum and energy), and also the inherent characteristics of the wireless transmission medium. Wireless transmission is in general subject to two phenomena: fading and interference. The el...

  3. Pelagic functional group modeling: Progress, challenges and prospects

    OpenAIRE

    Hood, RR; Laws, EA; Armstrong, RA; Bates, NR; Brown, CW; Carlson, CA; F. Chai; Doney, SC; Falkowski, PG; Feely, RA; Friedrichs, MAM; Landry, MR; Keith Moore, J; Nelson, DM; Richardson, TL

    2006-01-01

    In this paper, we review the state of the art and major challenges in current efforts to incorporate biogeochemical functional groups into models that can be applied on basin-wide and global scales, with an emphasis on models that might ultimately be used to predict how biogeochemical cycles in the ocean will respond to global warming. We define the term "biogeochemical functional group" to refer to groups of organisms that mediate specific chemical reactions in the ocean. Thus, according to ...

  4. Testing the predictive power of nuclear mass models

    International Nuclear Information System (INIS)

    A number of tests are introduced which probe the ability of nuclear mass models to extrapolate. Three models are analyzed in detail: the liquid drop model, the liquid drop model plus empirical shell corrections and the Duflo-Zuker mass formula. If predicted nuclei are close to the fitted ones, average errors in predicted and fitted masses are similar. However, the challenge of predicting nuclear masses in a region stabilized by shell effects (e.g., the lead region) is far more difficult. The Duflo-Zuker mass formula emerges as a powerful predictive tool

  5. Testing the predictive power of nuclear mass models

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza-Temis, J.; Morales, I. [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-543, Mexico 04510 D.F. (Mexico); Barea, J. [Center for Theoretical Physics, Sloane Physics Laboratory, Yale University, PO Box 208120, New Haven, CT 06520-8120 (United States); Frank, A. [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-543, Mexico 04510 D.F. (Mexico); Hirsch, J.G. [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-543, Mexico 04510 D.F. (Mexico)], E-mail: hirsch@nucleares.unam.mx; Vieyra, J.C. Lopez [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-543, Mexico 04510 D.F. (Mexico); Van Isacker, P. [Grand Accelerateur National d' Ions Lourds, CEA/DSM-CNRS/IN2P3, BP 55027, F-14076 Caen cedex 5 (France); Velazquez, V. [Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-543, Mexico 04510 D.F. (Mexico)

    2008-11-01

    A number of tests are introduced which probe the ability of nuclear mass models to extrapolate. Three models are analyzed in detail: the liquid drop model, the liquid drop model plus empirical shell corrections and the Duflo-Zuker mass formula. If predicted nuclei are close to the fitted ones, average errors in predicted and fitted masses are similar. However, the challenge of predicting nuclear masses in a region stabilized by shell effects (e.g., the lead region) is far more difficult. The Duflo-Zuker mass formula emerges as a powerful predictive tool.

  6. ROMANIAN STATISTICS – CURRENT CHALLENGES

    OpenAIRE

    Secareanu Constantin

    2009-01-01

    In the last decades, theoretical research and managerial practice have intensified and permitted the crystallization of some concepts, methods and new instruments for analysis and prediction of the status and evolution of a national statistical system. T

  7. Challenges of operational river forecasting

    NARCIS (Netherlands)

    Pagano, T.C.; Wood, A.W.; Ramos, M.H.; Cloke, H.L.; Pappenbreger, F.; Verkade, J.S.; et al.

    2014-01-01

    Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover

  8. Predicting the Lifetimes of Nuclear Waste Containers

    Science.gov (United States)

    King, Fraser

    2014-03-01

    As for many aspects of the disposal of nuclear waste, the greatest challenge we have in the study of container materials is the prediction of the long-term performance over periods of tens to hundreds of thousands of years. Various methods have been used for predicting the lifetime of containers for the disposal of high-level waste or spent fuel in deep geological repositories. Both mechanical and corrosion-related failure mechanisms need to be considered, although until recently the interactions of mechanical and corrosion degradation modes have not been considered in detail. Failure from mechanical degradation modes has tended to be treated through suitable container design. In comparison, the inevitable loss of container integrity due to corrosion has been treated by developing specific corrosion models. The most important aspect, however, is to be able to justify the long-term predictions by demonstrating a mechanistic understanding of the various degradation modes.

  9. The Mock LISA Data Challenges: from challenge 3 to challenge 4

    Energy Technology Data Exchange (ETDEWEB)

    Babak, Stanislav; Petiteau, Antoine; Robinson, Emma L [Max-Planck-Institut fuer Gravitationsphysik (Albert-Einstein-Institut), Am Muehlenberg 1, D-14476 Golm bei Potsdam (Germany); Baker, John G; McWilliams, Sean T; Arnaud, Keith A [Gravitational Astrophysics Laboratory, NASA Goddard Space Flight Center, 8800 Greenbelt Rd, Greenbelt, MD 20771 (United States); Benacquista, Matthew J [Center for Gravitational Wave Astronomy, University of Texas at Brownsville, Brownsville, TX 78520 (United States); Cornish, Neil J; Adams, Matt [Department of Physics, Montana State University, Bozeman, MT 59717 (United States); Larson, Shane L [Department of Physics, Utah State University, Logan, UT 84322 (United States); Mandel, Ilya [Department of Physics and Astronomy, Northwestern University, Evanston, IL (United States); Porter, Edward K [APC, UMR 7164, University Paris 7 Denis Diderot, 10, rue Alice Domon et Leonie Duquet, 75025 Paris Cedex 13 (France); Vallisneri, Michele; Cutler, Curt [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Vecchio, Alberto [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B152TT (United Kingdom); Blaut, Arkadiusz [Institute of Theoretical Physics, University of Wroclaw, Wroclaw (Poland); Bridges, Michael; Feroz, Farhan [Astrophysics Group, Cavendish Laboratory, University of Cambridge, Cambridge CB30HE (United Kingdom); Cohen, Michael [Theoretical Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Gair, Jonathan R., E-mail: Michele.Vallisneri@jpl.nasa.go [Institute of Astronomy, University of Cambridge, Cambridge CB30HA (United Kingdom)

    2010-04-21

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in April 2008, which demonstrated the positive recovery of signals from chirping galactic binaries, from spinning supermassive-black-hole binaries (with optimal SNRs between approx10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with OMEGA{sub gw}(f) approx 10{sup -11}, slightly below the LISA instrument noise.

  10. The Mock LISA Data Challenges: from Challenge 3 to Challenge 4

    CERN Document Server

    Babak, Stanislav; Benacquista, Matthew J; Cornish, Neil J; Larson, Shane L; Mandel, Ilya; Petiteau, Antoine; Porter, Edward K; Robinson, Emma L; Vallisneri, Michele; Vecchio, Alberto; Adams, Matt; Arnaud, Keith A; Błaut, Arkadiusz; Bridges, Michael; Cohen, Michael; Cutler, Curt; Feroz, Farhan; Gair, Jonathan R; Graff, Philip; Hobson, Mike; Key, Joey Shapiro; Królak, Andrzej; Lasenby, Anthony; Prix, Reinhard; Shang, Yu; Trias, Miquel; Veitch, John; Whelan, John T

    2009-01-01

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in Apr 2008, which demonstrated the positive recovery of signals from chirping Galactic binaries, from spinning supermassive--black-hole binaries (with optimal SNRs between ~ 10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Omega_gw(f) ~ 10^-11, slightly below the LISA instrument noise.

  11. The Mock LISA Data Challenges: from challenge 3 to challenge 4

    International Nuclear Information System (INIS)

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in April 2008, which demonstrated the positive recovery of signals from chirping galactic binaries, from spinning supermassive-black-hole binaries (with optimal SNRs between ∼10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Ωgw(f) ∼ 10-11, slightly below the LISA instrument noise.

  12. Evaluating Link Prediction Accuracy on Dynamic Networks with Added and Removed Edges

    CERN Document Server

    Junuthula, Ruthwik R; Devabhaktuni, Vijay K

    2016-01-01

    The task of predicting future relationships in a social network, known as link prediction, has been studied extensively in the literature. Many link prediction methods have been proposed, ranging from common neighbors to probabilistic models. Recent work by Yang et al. has highlighted several challenges in evaluating link prediction accuracy. In dynamic networks where edges are both added and removed over time, the link prediction problem is more complex and involves predicting both newly added and newly removed edges. This results in new challenges in the evaluation of dynamic link prediction methods, and the recommendations provided by Yang et al. are no longer applicable, because they do not address edge removal. In this paper, we investigate several metrics currently used for evaluating accuracies of dynamic link prediction methods and demonstrate why they can be misleading in many cases. We provide several recommendations on evaluating dynamic link prediction accuracy, including separation into two categ...

  13. Monitoring challenges and innovative ideas

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, R.V.; Hunsaker, C.T.; Levine, D.A.

    1990-01-01

    Monitoring programs are difficult to design even when they focus on specific problems. Ecosystems are complex, and it is often impossible to predetermine what aspects of system structure or dynamics will respond to a specific insult. It is equally difficult to interpret whether a response is a stabilizing compensatory mechanism or a real loss of capacity to maintain the ecosystem. The problems are compounded in a broad monitoring program designed to assess ecosystem health'' at regional and continental scales. It is challenging in the extreme to monitor ecosystem response, at any scale, to past insults as well as an unknown future array of impacts. The present paper will examine some of the fundamental issues and challenges raised by large-scale monitoring efforts. The challenges will serve as a framework and as an excuse to discuss several important topics in more detail. Following the discussion of challenges, we suggest some basic innovations that could be important across a range of monitoring programs. The innovations include integrative measures, innovative methodology, and creative interpretation. 59 refs., 1 tab.

  14. They rose to the challenge!

    CERN Multimedia

    Anaïs Schaeffer

    2015-01-01

    The Challenge-Based Innovation programme is a Masters-level initiative developed at CERN in collaboration with many universities around the world. The first programme saw 45 students take part, and their final results were presented at an official "gala" held on 26 February.   On 26 February, after their official presentations, the six CBI teams presented their prototypes to the public in the IdeaSquare building.   As part of the IdeaSquare project, the Challenge-Based Innovation (CBI) programme is based on a very pragmatic question: can the tools and results produced by basic research (like that being carried out at CERN) be used to solve societal problems? If so, how? To answer this question, 45 students from very different professional and cultural backgrounds formed six teams, each with a specific societal challenge to solve (see here). Over a six-month period – from September 2014 to February 2015 – the six teams worked on the challenge in o...

  15. The Concrete and Pavement Challenge

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    The modern world is characterized by the extensive use of concrete and asphalt pavement. Periodically, these materials are replaced and the old materials disposed of. In this challenge, students will be asked to develop ways to reuse the old materials. It is important for students to understand how concrete and asphalt are made and applied, as…

  16. Challenges for cancer vaccine development.

    Science.gov (United States)

    Tabi, Z; Man, S

    2006-10-01

    The first generation of human cancer vaccines has been tested in phase III clinical trials, but only a few of these have demonstrated sufficient efficacy to be licensed for clinical use. This article reviews some of the mechanisms that could contribute to these limited clinical responses, and highlights the challenges faced for development of future vaccines. PMID:16979786

  17. Challenging Sexual Harassment on Campus

    Science.gov (United States)

    Baker, Nancy V.

    2010-01-01

    More than thirty years ago, an administrative assistant at Cornell University first challenged her university's indifference to her boss's sexually predatory behavior. While she did not prevail, her case sparked a movement. Litigation, news stories, and government guidelines defining sexual harassment followed. And universities responded: policies…

  18. Tuberculosis 2004: Challenges and Opportunities

    OpenAIRE

    Glassroth, Jeffrey

    2005-01-01

    Tuberculosis (TB) continues as a major public health challenge worldwide. HIV-TB coinfection is especially concerning as it accelerates progression of infection to active disease and amplifies spread of TB including drug resistant disease. Application of molecular biology and insights from classic microbiology to TB control have resulted in important innovations in diagnosis and treatment.

  19. CHALLENGES FACING THE ESP PRACTITIONER

    Directory of Open Access Journals (Sweden)

    SIMION MINODORA OTILIA

    2015-12-01

    Full Text Available The ESP teacher has to face certain challenges in his profession: One of the biggest challenges of the ESP teacher is the fact that he/she lacks the necessary knowledge of the subject to teach Business English, for instance, some researchers believing that such courses should be taught by subject teachers. The task of teaching ESP by ESL teachers is not an easy one. Dudley- Evans and St. John pointed out its complexity, identifying five key roles of the ESP practitioner: teacher, course designer and materials provider, collaborator, researcher and evaluator and this is probably the biggest challenge of the profession. The ESP practitioner has also to be aware of the fact that using a foreign language for workplace or study purposes requires not only linguistic proficiency and knowledge but also knowledge of work –related and disciplinary concepts.Last but not least, another challenge for the ESP practitioner is the use of technology in class, a valuable tool for helping with traditional forms of teaching and for creating new forms of communicating.Thus, the ESP practitioner has many things in common with the teacher of general English: he has to be familiar with linguistic development and teaching theories ,he has to be aware of contemporary ideas related to his position and role and he has to become familiar with the new technologies which can be used to improve his methodology.However,his role is more complex than that of a General English teacher.

  20. Plain language and organisational challenges

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    2014-01-01

    Changing the language in an organization is a major organizational change. In this article, I discuss some of the organizational challenges for one specific language change implementation, taking the stance that language change must be treated as any other organizational change for it to have an ...

  1. The Real Challenge of ESD

    Science.gov (United States)

    Jackson, M. G.

    2011-01-01

    Between the Inter-governmental Conference on Environmental Education at Tbilisi in 1977 and the Fourth International Conference on Environmental Education at Ahmedabad in 2007, our conception of the challenge posed by the global crises of climate change, environmental destruction, social disintegration, poverty, natural resources exhaustion and…

  2. Challenges of blended-learning

    OpenAIRE

    Lugovtsova, Y. D.; Mylnikova, Tatyana Stepanovna

    2014-01-01

    Creation of the virtual environment as an educational resource to increase motivation and inquisition of the students is a great challenge for Russian educational system. The paper considers some issues of blended-learning. Some elements of blended-learning are analyzed through the ways they are implemented in Tomsk Polytechnic University.

  3. Climate Change: Meeting the Challenge

    Science.gov (United States)

    Chance, Paul; Heward, William L.

    2010-01-01

    In "Climate Change: Meeting the Challenge," we conclude the special section by assuming that you have been persuaded by Thompson's paper or other evidence that global warming is real and poses a threat that must be dealt with, and that for now the only way to deal with it is by changing behavior. Then we ask what you, as behavior analysts, can do…

  4. Efficient audio power amplification - challenges

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Michael A.E.

    2005-07-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extensive research and development are needed is covered. (au)

  5. The Speeding Car Design Challenge

    Science.gov (United States)

    Roman, Harry T.

    2009-01-01

    All too often, one reads about high-speed police chases in pursuit of stolen cars that result in death and injury to people and innocent bystanders. Isn't there another way to accomplish the apprehension of the thieves that does not put people at such great risk? This article presents a classroom challenge to use technology to remotely shutdown…

  6. The Health and Fitness Challenge.

    Science.gov (United States)

    Snelling, Anastasia M.

    1999-01-01

    "Health and Fitness Challenge" program was implemented using the "social marketing model" to raise awareness of health education and related services to students. Collaboration between faculty, student affairs professionals, and students occurred from design through evaluation. The primary goal of bringing students, faculty and staff together was…

  7. Accountability: new challenges, new forms

    NARCIS (Netherlands)

    C. van Woerkum; N. Aarts

    2012-01-01

    The general call for more accountability, affecting all western institutions, has reached the communication professionals as well. How can they cope with this new challenge? The danger is that they focus mainly on outcomes, so on performative accountability, whereas decisional accountability, meanin

  8. Challenges to 5G standardization

    DEFF Research Database (Denmark)

    Mihovska, Albena D.; Prasad, Ramjee

    2013-01-01

    Interoperable, ubiquitous and dynamic are key objectives for fifth-generation (5G) communication systems and applications. These characteristics are also at the core of the main challenges that researchers, manufacturers, regulators and standardization bodies face when designing targeted strategies...... for the successful deployment of 5G enabling technologies....

  9. A Water-Service Challenge

    Science.gov (United States)

    Roman, Harry T.

    2011-01-01

    It is important to let students see the value of mathematics in design--and how mathematics lends perspective to problem solving. In this article, the author describes a water-service challenge which enables students to design a water utility system that uses surface runoff into an open reservoir as the potable water source. This challenge…

  10. NASA Space Rocket Logistics Challenges

    Science.gov (United States)

    Neeley, James R.; Jones, James V.; Watson, Michael D.; Bramon, Christopher J.; Inman, Sharon K.; Tuttle, Loraine

    2014-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle and is scheduled for its first mission in 2017. The goal of the first mission, which will be uncrewed, is to demonstrate the integrated system performance of the SLS rocket and spacecraft before a crewed flight in 2021. SLS has many of the same logistics challenges as any other large scale program. Common logistics concerns for SLS include integration of discreet programs geographically separated, multiple prime contractors with distinct and different goals, schedule pressures and funding constraints. However, SLS also faces unique challenges. The new program is a confluence of new hardware and heritage, with heritage hardware constituting seventy-five percent of the program. This unique approach to design makes logistics concerns such as commonality especially problematic. Additionally, a very low manifest rate of one flight every four years makes logistics comparatively expensive. That, along with the SLS architecture being developed using a block upgrade evolutionary approach, exacerbates long-range planning for supportability considerations. These common and unique logistics challenges must be clearly identified and tackled to allow SLS to have a successful program. This paper will address the common and unique challenges facing the SLS programs, along with the analysis and decisions the NASA Logistics engineers are making to mitigate the threats posed by each.

  11. Efficient Audio Power Amplification - Challenges

    DEFF Research Database (Denmark)

    Andersen, Michael Andreas E.

    2005-01-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where...

  12. The Kiki-Bouba Challenge

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Collins, Nick

    2014-01-01

    We propose the “Kiki-Bouba Challenge” (KBC) for the re- search and development of content-based music informa- tion retrieval (MIR) systems. This challenge is unencum- bered by several problems typically encountered in MIR research: insufficient data, restrictive copyrights, imper- fect ground...

  13. Training Information Consumers: Today's Challenge.

    Science.gov (United States)

    Gordon, Dena W.

    The revolution in the information environment caused by new technology is making the training of information consumers a major challenge for publishers of business-targeted databases and vendors of online systems. Research conducted by Data Courier in 1981 and 1982 suggests that online searching by information consumers will continue to increase.…

  14. Challenges in a Physics Course

    DEFF Research Database (Denmark)

    Hernández, Carola Hernández; Ravn, Ole; Forero Shelton, Antonio Manu

    2014-01-01

    This article identifies and analyses some of the challenges that arose in a development process of changing from a content-based teaching environment to a student-centred environment in an undergraduate physics course for medicine and biology students at Universidad de los Andes. Through the use...

  15. 'Red Flag' Predictions

    DEFF Research Database (Denmark)

    Hallin, Carina Antonia; Andersen, Torben Juul; Tveterås, Sigbjørn

    -generation prediction markets and outline its unique features as a third-generation prediction market. It is argued that frontline employees gain deep insights when they execute operational activities on an ongoing basis in the organization. The experiential learning from close interaction with internal and external...

  16. Predicting the MJO

    Science.gov (United States)

    Hendon, H.

    2003-04-01

    Extended range prediction of the Madden Julian Oscillation (MJO) and seasonal prediction of MJO activity are reviewed. Skillful prediction of individual MJO events offers the possibility of forecasting increased risk of cyclone development throughout the global tropics, altered risk of extreme rainfall events in both tropics and extratropics, and displacement of storm tracks with 3-4 week lead times. The level of MJO activity within a season, which affects the mean intensity of the Australian summer monsoon and possibly the evolution of ENSO, may be governed by variations of sea surface temperature that are predictable with lead times of a few seasons. The limit of predictability for individual MJO events is unknown. Empirical-statistical schemes are skillful out to about 3 weeks and have better skill than dynamical forecast models at lead times longer than about 5 days. The dynamical forecast models typically suffer from a poor representation (or complete lack) of the MJO and large initial error. They are better used to ascertain the global impacts of the lack of the MJO rather than for determination of the limit of predictability. Dynamical extended range prediction within a GCM that has a good representation of the MJO indicates potential skill comparable to the empirical schemes. Examples of operational extended range prediction with POAMA, the new coupled seasonal forecast model at the Bureau of Meteorology that also reasonably simulates the MJO, will be presented.

  17. Improved nonlinear prediction method

    Science.gov (United States)

    Adenan, Nur Hamiza; Md Noorani, Mohd Salmi

    2014-06-01

    The analysis and prediction of time series data have been addressed by researchers. Many techniques have been developed to be applied in various areas, such as weather forecasting, financial markets and hydrological phenomena involving data that are contaminated by noise. Therefore, various techniques to improve the method have been introduced to analyze and predict time series data. In respect of the importance of analysis and the accuracy of the prediction result, a study was undertaken to test the effectiveness of the improved nonlinear prediction method for data that contain noise. The improved nonlinear prediction method involves the formation of composite serial data based on the successive differences of the time series. Then, the phase space reconstruction was performed on the composite data (one-dimensional) to reconstruct a number of space dimensions. Finally the local linear approximation method was employed to make a prediction based on the phase space. This improved method was tested with data series Logistics that contain 0%, 5%, 10%, 20% and 30% of noise. The results show that by using the improved method, the predictions were found to be in close agreement with the observed ones. The correlation coefficient was close to one when the improved method was applied on data with up to 10% noise. Thus, an improvement to analyze data with noise without involving any noise reduction method was introduced to predict the time series data.

  18. Zephyr - the prediction models

    DEFF Research Database (Denmark)

    Nielsen, Torben Skov; Madsen, Henrik; Nielsen, Henrik Aalborg;

    2001-01-01

    utilities as partners and users. The new models are evaluated for five wind farms in Denmark as well as one wind farm in Spain. It is shown that the predictions based on conditional parametric models are superior to the predictions obatined by state-of-the-art parametric models....

  19. Predicting AD conversion

    DEFF Research Database (Denmark)

    Liu, Yawu; Mattila, Jussi; Ruiz, Miguel �ngel Mu�oz;

    2013-01-01

    To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI...

  20. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  1. Error mode prediction.

    Science.gov (United States)

    Hollnagel, E; Kaarstad, M; Lee, H C

    1999-11-01

    The study of accidents ('human errors') has been dominated by efforts to develop 'error' taxonomies and 'error' models that enable the retrospective identification of likely causes. In the field of Human Reliability Analysis (HRA) there is, however, a significant practical need for methods that can predict the occurrence of erroneous actions--qualitatively and quantitatively. The present experiment tested an approach for qualitative performance prediction based on the Cognitive Reliability and Error Analysis Method (CREAM). Predictions of possible erroneous actions were made for operators using different types of alarm systems. The data were collected as part of a large-scale experiment using professional nuclear power plant operators in a full scope simulator. The analysis showed that the predictions were correct in more than 70% of the cases, and also that the coverage of the predictions depended critically on the comprehensiveness of the preceding task analysis. PMID:10582035

  2. Evaluating prediction uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    McKay, M.D. [Los Alamos National Lab., NM (United States)

    1995-03-01

    The probability distribution of a model prediction is presented as a proper basis for evaluating the uncertainty in a model prediction that arises from uncertainty in input values. Determination of important model inputs and subsets of inputs is made through comparison of the prediction distribution with conditional prediction probability distributions. Replicated Latin hypercube sampling and variance ratios are used in estimation of the distributions and in construction of importance indicators. The assumption of a linear relation between model output and inputs is not necessary for the indicators to be effective. A sequential methodology which includes an independent validation step is applied in two analysis applications to select subsets of input variables which are the dominant causes of uncertainty in the model predictions. Comparison with results from methods which assume linearity shows how those methods may fail. Finally, suggestions for treating structural uncertainty for submodels are presented.

  3. Evaluating prediction uncertainty

    International Nuclear Information System (INIS)

    The probability distribution of a model prediction is presented as a proper basis for evaluating the uncertainty in a model prediction that arises from uncertainty in input values. Determination of important model inputs and subsets of inputs is made through comparison of the prediction distribution with conditional prediction probability distributions. Replicated Latin hypercube sampling and variance ratios are used in estimation of the distributions and in construction of importance indicators. The assumption of a linear relation between model output and inputs is not necessary for the indicators to be effective. A sequential methodology which includes an independent validation step is applied in two analysis applications to select subsets of input variables which are the dominant causes of uncertainty in the model predictions. Comparison with results from methods which assume linearity shows how those methods may fail. Finally, suggestions for treating structural uncertainty for submodels are presented

  4. Predictable return distributions

    DEFF Research Database (Denmark)

    Pedersen, Thomas Quistgaard

    This paper provides detailed insights into predictability of the entire stock and bond return distribution through the use of quantile regression. This allows us to examine speci…c parts of the return distribution such as the tails or the center, and for a suf…ciently …ne grid of quantiles we can...... predictable as a function of economic state variables. The results are, however, very different for stocks and bonds. The state variables primarily predict only location shifts in the stock return distribution, while they also predict changes in higher-order moments in the bond return distribution. Out......-of-sample analyses show that the relative accuracy of the state variables in predicting future returns varies across the distribution. A portfolio study shows that an investor with power utility can obtain economic gains by applying the empirical return distribution in portfolio decisions instead of imposing an...

  5. Is Time Predictability Quantifiable?

    DEFF Research Database (Denmark)

    Schoeberl, Martin

    2012-01-01

    Computer architects and researchers in the realtime domain start to investigate processors and architectures optimized for real-time systems. Optimized for real-time systems means time predictable, i.e., architectures where it is possible to statically derive a tight bound of the worst-case execu......Computer architects and researchers in the realtime domain start to investigate processors and architectures optimized for real-time systems. Optimized for real-time systems means time predictable, i.e., architectures where it is possible to statically derive a tight bound of the worst......-case execution time. To compare different approaches we would like to quantify time predictability. That means we need to measure time predictability. In this paper we discuss the different approaches for these measurements and conclude that time predictability is practically not quantifiable. We can only...

  6. Ground motion predictions

    International Nuclear Information System (INIS)

    Nuclear generated ground motion is defined and then related to the physical parameters that cause it. Techniques employed for prediction of ground motion peak amplitude, frequency spectra and response spectra are explored, with initial emphasis on the analysis of data collected at the Nevada Test Site (NTS). NTS postshot measurements are compared with pre-shot predictions. Applicability of these techniques to new areas, for example, Plowshare sites, must be questioned. Fortunately, the Atomic Energy Commission is sponsoring complementary studies to improve prediction capabilities primarily in new locations outside the NTS region. Some of these are discussed in the light of anomalous seismic behavior, and comparisons are given showing theoretical versus experimental results. In conclusion, current ground motion prediction techniques are applied to events off the NTS. Predictions are compared with measurements for the event Faultless and for the Plowshare events, Gasbuggy, Cabriolet, and Buggy I. (author)

  7. Crowd Sourcing for Challenging Technical Problems and Business Model

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth

    2011-01-01

    Crowd sourcing may be defined as the act of outsourcing tasks that are traditionally performed by an employee or contractor to an undefined, generally large group of people or community (a crowd) in the form of an open call. The open call may be issued by an organization wishing to find a solution to a particular problem or complete a task, or by an open innovation service provider on behalf of that organization. In 2008, the Space Life Sciences Directorate (SLSD), with the support of Wyle Integrated Science and Engineering, established and implemented pilot projects in open innovation (crowd sourcing) to determine if these new internet-based platforms could indeed find solutions to difficult technical challenges. These unsolved technical problems were converted to problem statements, also called "Challenges" or "Technical Needs" by the various open innovation service providers, and were then posted externally to seek solutions. In addition, an open call was issued internally to NASA employees Agency wide (10 Field Centers and NASA HQ) using an open innovation service provider crowd sourcing platform to post NASA challenges from each Center for the others to propose solutions). From 2008 to 2010, the SLSD issued 34 challenges, 14 externally and 20 internally. The 14 external problems or challenges were posted through three different vendors: InnoCentive, Yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive crowd sourcing platform designed for internal use by an organization. This platform was customized for NASA use and promoted as NASA@Work. The results were significant. Of the seven InnoCentive external challenges, two full and five partial awards were made in complex technical areas such as predicting solar flares and long-duration food packaging. Similarly, the TopCoder challenge yielded an optimization algorithm for designing a lunar medical kit. The Yet2.com challenges yielded many new industry and academic contacts in bone

  8. Success of Breast Cancer Startup Challenge Inspires Second Challenge | Poster

    Science.gov (United States)

    By Thomas Stackhouse, Joseph Conrad, and Michele Newton, Contributing Writers, and Rosemarie Truman, Guest Writer Sixty-one teams have been accepted into, and are now competing in, the Neuro Startup Challenge, a new collaboration established by the National Institutes of Health (NIH) with The Center for Advancing Innovation (CAI) and Heritage Provider Network, Inc.

  9. Structural prediction in aphasia

    Directory of Open Access Journals (Sweden)

    Tessa Warren

    2015-05-01

    Full Text Available There is considerable evidence that young healthy comprehenders predict the structure of upcoming material, and that their processing is facilitated when they encounter material matching those predictions (e.g., Staub & Clifton, 2006; Yoshida, Dickey & Sturt, 2013. However, less is known about structural prediction in aphasia. There is evidence that lexical prediction may be spared in aphasia (Dickey et al., 2014; Love & Webb, 1977; cf. Mack et al, 2013. However, predictive mechanisms supporting facilitated lexical access may not necessarily support structural facilitation. Given that many people with aphasia (PWA exhibit syntactic deficits (e.g. Goodglass, 1993, PWA with such impairments may not engage in structural prediction. However, recent evidence suggests that some PWA may indeed predict upcoming structure (Hanne, Burchert, De Bleser, & Vashishth, 2015. Hanne et al. tracked the eyes of PWA (n=8 with sentence-comprehension deficits while they listened to reversible subject-verb-object (SVO and object-verb-subject (OVS sentences in German, in a sentence-picture matching task. Hanne et al. manipulated case and number marking to disambiguate the sentences’ structure. Gazes to an OVS or SVO picture during the unfolding of a sentence were assumed to indicate prediction of the structure congruent with that picture. According to this measure, the PWA’s structural prediction was impaired compared to controls, but they did successfully predict upcoming structure when morphosyntactic cues were strong and unambiguous. Hanne et al.’s visual-world evidence is suggestive, but their forced-choice sentence-picture matching task places tight constraints on possible structural predictions. Clearer evidence of structural prediction would come from paradigms where the content of upcoming material is not as constrained. The current study used self-paced reading study to examine structural prediction among PWA in less constrained contexts. PWA (n=17 who

  10. Effects of mesh resolution on hypersonic heating prediction

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Aeroheating prediction is a challenging and critical problem for the design and optimization of hypersonic vehicles.One challenge is that the solution of the Navier-Stokes equations strongly depends on the computational mesh.In this letter,the effect of mesh resolution on heat flux prediction is studied.It is found that mesh-independent solutions can be obtained using fine mesh,whose accuracy is confirmed by results from kinetic particle simulation.It is analyzed that mesh-induced numerical error comes m...

  11. Predicting E-commerce Consumer Behaviour Using Sparse Session Data

    OpenAIRE

    Thorrud, Thorstein Kaldahl; Myklatun, Øyvind

    2015-01-01

    This thesis research consumer behavior in an e-commerce domain by using a data set of sparse session data collected from an anonymous European e-commerce site. The goal is to predict whether a consumer session results in a purchase, and if so, which items are purchased. The data is supplied by the ACM Recommender System Challenge, which is a yearly challenge held by the ACM Recommender System Conference. Classification is used for predicting whether or not a session made a purchase, as w...

  12. Predicting geomagnetic activity indices

    International Nuclear Information System (INIS)

    Complete text of publication follows. Magnetically active times, e.g., Kp > 5, are notoriously difficult to predict, precisely the times when such predictions are crucial to the space weather users. Taking advantage of the routinely available solar wind measurements at Lagrangian point (L1) and nowcast Kps, Kp and Dst forecast models based on neural networks were developed with the focus on improving the forecast for active times. To satisfy different needs and operational constraints, three models were developed: (1) a model that inputs nowcast Kp and solar wind parameters and predicts Kp 1 hr ahead; (2) a model with the same input as model 1 and predicts Kp 4 hr ahead; and (3) a model that inputs only solar wind parameters and predicts Kp 1 hr ahead (the exact prediction lead time depends on the solar wind speed and the location of the solar wind monitor.) Extensive evaluations of these models and other major operational Kp forecast models show that, while the new models can predict Kps more accurately for all activities, the most dramatic improvements occur for moderate and active times. Similar Dst models were developed. Information dynamics analysis of Kp, suggests that geospace is more dominated by internal dynamics near solar minimum than near solar maximum, when it is more directly driven by external inputs, namely solar wind and interplanetary magnetic field (IMF).

  13. On Prediction of EOP

    CERN Document Server

    Malkin, Z

    2009-01-01

    Two methods of prediction of the Pole coordinates and TAI-UTC were tested -- extrapolation of the deterministic components and ARIMA. It was found that each of these methods is most effective for certain length of prognosis. For short-time prediction ARIMA algorithm yields more accurate prognosis, and for long-time one extrapolation is preferable. So, the combined algorithm is being used in practice of IAA EOP Service. The accuracy of prognosis is close to accuracy of IERS algorithms. For prediction of nutation the program KSV-1996-1 by T. Herring is being used.

  14. Challenges in Complex Systems Science

    CERN Document Server

    Miguel, Maxi San; Kertesz, Janos; Kaski, Kimmo; Díaz-Guilera, Albert; MacKay, Robert S; Loreto, Vittorio; Erdi, Peter; Helbing, Dirk

    2012-01-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneou...

  15. The Higgs Machine Learning Challenge

    Science.gov (United States)

    Adam-Bourdarios, C.; Cowan, G.; Germain-Renaud, C.; Guyon, I.; Kégl, B.; Rousseau, D.

    2015-12-01

    The Higgs Machine Learning Challenge was an open data analysis competition that took place between May and September 2014. Samples of simulated data from the ATLAS Experiment at the LHC corresponding to signal events with Higgs bosons decaying to τ+τ- together with background events were made available to the public through the website of the data science organization Kaggle (kaggle.com). Participants attempted to identify the search region in a space of 30 kinematic variables that would maximize the expected discovery significance of the signal process. One of the primary goals of the Challenge was to promote communication of new ideas between the Machine Learning (ML) and HEP communities. In this regard it was a resounding success, with almost 2,000 participants from HEP, ML and other areas. The process of understanding and integrating the new ideas, particularly from ML into HEP, is currently underway.

  16. Terahertz applications: trends and challenges

    Science.gov (United States)

    Robin, Thierry; Bouye, Clementine; Cochard, Jacques

    2014-03-01

    The objective of our work [1] was to determine the opportunities and challenges for Terahertz application development for the next years with a focus on systems: for homeland security and for Non Destructive Testing (NDT). Terahertz radiation has unique abilities and has been the subject of extensive research for many years. Proven concepts have emerged for numerous applications including Industrial NDT, Security, Health, Telecommunications, etc. Nevertheless, there has been no widely deployed application and Businesses based on THz technologies are still in their infancy. Some technological, market and industrial barriers are still to be broken. We summarize the final analysis and data: study of the technology trends and major bottlenecks per application segment, main challenges to be addressed in the next years, key opportunities for THz technologies based on market needs and requirements.

  17. The Higgs Machine Learning Challenge

    CERN Document Server

    Cowan, Glen; Adam-Bourdarios, C; Kégl, B; Rousseau, D; Germain-Renaud, C; Guyon, I

    2015-01-01

    The Higgs Machine Learning Challenge was an open data analysis competition that took place between May and September 2014. Samples of simulated data from the ATLAS Experiment at the LHC corresponding to signal events with Higgs bosons decaying to $\\tau^+\\tau^-$ together with background events were made available to the public through the website of the data science organization Kaggle (\\verb=kaggle.com=). Participants attempted to identify the search region in a space of 30 kinematic variables that would maximize the expected discovery significance of the signal process. One of the primary goals of the Challenge was promote communication of new ideas between the Machine Learning (ML) and HEP communities. In this regard it was a resounding success, with almost 2,000 participants from HEP, ML and other areas. The process of understanding and integrating the new ideas, particularly from ML into HEP, is currently underway.

  18. Challenges in pediatric endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Vikas Mittal

    2014-01-01

    Full Text Available We performed endothelial keratoplasty (EK in three eyes of two siblings (2.5 years, male and 3.5 years, female with congenital hereditary endothelial dystrophy (CHED and report the intraoperative and postoperative difficulties. Repeated iris prolapse, apprehension of crystalline lens touch due to positive vitreous pressure, and need for frequent air injections to attach the graft were intraoperative challenges in all three eyes. These were addressed by use of Sheet′s glide instead of Busin′s glide during graft insertion and suturing of main and side ports before air injection. One eye had graft dislocation on second postoperative day due to eye rubbing by the child. Graft was repositioned with air and a venting incision was created. Postoperative examination required repeated general anesthesia. Corneal edema resolved completely in all three eyes. Present case series highlights the possible intraoperative and postoperative challenges and their solutions in pediatric EK for CHED.

  19. Challenges for Research on Intelligence

    Directory of Open Access Journals (Sweden)

    Earl Hunt

    2013-10-01

    Full Text Available After 100 years of research, the definition of the field is still inadequate. The biggest challenge we see is moving away from a de-factor definition of intelligence in terms of test scores, but at the same time making clear what the boundaries of the field are. We then present four challenges for the field, two within a biological and two within a social context. These revolve around the issues of the malleability of intelligence and its display in everyday life, outside of a formal testing context. We conclude that developments in cognitive neuroscience and increases in the feasibility of monitoring behavior outside of the context of a testing session offer considerable hope for expansion of our both the biological and social aspects of individual differences in cognition.

  20. Challenges of Human Space Flight

    Science.gov (United States)

    Davis, Jeffrey R.; Charles, John B.

    2006-01-01

    The presentations will be given during the X-Prize symposium, exploring the multi-faceted dimensions of spaceflight ranging from the technical developments necessary to achieve safe routine flight to and from and through space to the new personal business opportunities and economic benefits that will open in space and here on Earth. The symposium will delve into the technical, regulatory, market and financial needs and challenges that must be met in charting and executing the incremental developments leading to Personal Spaceflight and the opening of a Place Called Space. The presentation covers facets of human space flight including descriptions of life in space, the challenges of delivering medical care in space, and the preparations needed for safe and productive human travel to the moon and Mars.

  1. Embracing the challenge of competition

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, C. [Edmonton Power Inc., Edmonton, AB (Canada)

    1998-07-01

    The new and creative solutions that Edmonton Power is using to meet the challenges of deregulation, competition and demand for customer choice in the electric power industry are discussed. Among these creative initiatives, in 1997 Edmonton Power extended account management services to 850 accounts to deliver commercial and operational analysis of energy consumption and management. Another major focus of effort has been the introduction of time of use (TOU) pricing options to commercial and industrial customers above 150 kWh. This required the installation of the latest hourly metering technology and the establishment of new price plans and contracts. Two major challenges were highlighted: (1) the mismatch between the prices utilities pay at the power pool and what the customer pays at the meter, and (2) the increased volatility of hour to hour price changes are just some of the risks that will have to be resolved under the new market structure.

  2. The challenge of financing nuclear power plants

    International Nuclear Information System (INIS)

    To date, more then 500 nuclear power reactors have been successfully financed and built. Experience in recent nuclear projects confirms that nuclear power will not cease to be a viable option due to a worldwide financing constraint. For financing nuclear plants there are special considerations: large investment; long lead and construction times; complex technology; regulatory risk and political risk. The principal preconditions to financing are a national policy supporting nuclear power; creditworthiness; economic competitiveness; project feasibility; assurance of adequate revenues; acceptability of risks; and no open-ended liabilities. Generally, nuclear power plants are financed conventionally through multi-sources, where a package covers the entire cost. The first source, the investor/owner/operator responsible for building and operating the plant, should cover a sizable portion of the overall investment. In addition, bond issues, domestic bank credits etc. and, in case of State-owned or controlled enterprises, donations and credits from public entities or the governmental budget, should complete the financing. A financially sound utility should be able to meet this challenge. For importing technology, bids are invited. Export credits should form the basis of foreign financing, because these have favorable terms and conditions. Suppliers from several countries may join in a consortium subdividing the scope of supply and involve several Export Credit Agencies (ECAs). There are also innovative financing approaches that could be applied to nuclear projects. Evolutionary Reactors with smaller overall investment, shorter construction times, reliance on proven technology, together with predictable regulatory regimes and reliable long-term national policies favorable to nuclear power, should make it easier to meet the future challenges of financing. (author)

  3. Structural materials challenges for fusion power systems

    International Nuclear Information System (INIS)

    Full text: Structural materials in a fusion power system must function in an extraordinarily demanding environment that includes various combinations of high temperatures, reactive chemicals, time-dependent thermal and mechanical stresses, and intense damaging radiation. The fusion neutron environment produces displacement damage equivalent to displacing every atom in the material about 150 times during its expected service life, and changes in chemical composition by transmutation reactions, which includes creation of reactive and insoluble gases. Fundamental materials challenges that must be resolved to effectively harness fusion power include (1) understanding the relationships between material strength, ductility and resistance to cracking, (2) development of materials with extraordinary phase stability, high-temperature strength and resistance to radiation damage, (3) establishment of the means to control corrosion of materials exposed to aggressive environments, (4) development of technologies for large-scale fabrication and joining, and (5) design of structural materials that provide for an economically attractive fusion power system while simultaneously achieving safety and environmental acceptability goals. The most effective approach to solve these challenges is a science-based effort that couples development of physics-based, predictive models of materials behavior with key experiments to validate the models. The U.S. Fusion Materials Sciences program is engaged in an integrated effort of theory, modeling and experiments to develop structural materials that will enable fusion to reach its safety, environmental and economic competitiveness goals. In this presentation, an overview of recent progress on reduced activation ferritic/martensitic steels, nanocomposited ferritic alloys, and silicon carbide fiber reinforced composites for fusion applications will be given

  4. Challenges in Regulating Pesticide Mixtures

    OpenAIRE

    Debra Denton; Bruce Hammock; Craig Wheelock; Jason Belden; Michael Lydy

    2004-01-01

    This paper introduces the field of mixture toxicity and the challenges in regulating pesticide mixtures. Even though pesticides are unique chemical stressors designed to have biological activity that can affect a number of nontarget species, they are intentionally placed into the environment in large quantities. Currently, methods and terminology for evaluating mixture toxicity are poorly established. The most common approach used is the assumption of additive concentration, with the concentr...

  5. ETHICAL CHALLENGES IN AESTHETIC DENTISTRY

    OpenAIRE

    Marius NEAGU; Bianca HANGANU; Magdalena IORGA; Beatrice IOAN

    2015-01-01

    Aesthetic dentistry is a branch of dentistry which aims primarily at improving patient’s physical appearance and, to a lesser extent, the functionality of teeth. This field raises particular ethical dilemmas and requires a careful evaluation of patient’s needs and wishes versus his/her clinical best interests. In this article, the authors discuss the main ethical challenges in the field of aesthetic dentistry in the light of the four “classical” principles of bioethics: autonomy, beneficence,...

  6. The challenges of managing migration

    Energy Technology Data Exchange (ETDEWEB)

    Tacoli, Cecilia

    2005-10-15

    Migration and urbanisation are driven by economic growth and social change, but also by deepening inequalities. Managing migration should not be equated with curbing it, as this inevitably reduces migrants' rights. But managing population movement whilst respecting the rights of migrants and nonmigrants, supporting the contribution of migration to poverty reduction and economic growth in sending and receiving areas and reducing the human and material costs of movement means that fundamental challenges need to be addressed.

  7. Computational photography: advances and challenges

    OpenAIRE

    Lam, EYM

    2011-01-01

    In the mid-1990s when digital photography began to enter the consumer market, Professor Joseph Goodman and I set out to explore how computation would impact the imaging system design. The field of study has since grown to be known as computational photography. In this paper I'll describe some of its recent advances and challenges, and discuss what the future holds. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

  8. Diagnostic challenges in celiac disease

    Directory of Open Access Journals (Sweden)

    M Haghighat

    2014-04-01

    Full Text Available   1-The most important challenge in diagnosis of celiac disease is not- performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be awared about uncommon presentations of disease and indications of celiac tests 2-The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3- The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing  for DQ8 and  DQ2 should be done. 4-The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN , positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5-In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6-In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7-Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.  

  9. Economic challenges in the Anthropocene

    OpenAIRE

    Musu, Ignazio

    2013-01-01

    The evolution during the Anthropocene is analyzed through the interaction between economic and technological development, characterized by the role of fossil fuels and by the progressive dominance of those with a higher energy and density power. The challenge is how to make the rising demand for economic growth, mainly coming from developing and emerging countries, compatible with the sustainability of the processes concerning the Earth system. Mainly by focusing on the energy-environment cha...

  10. Challenges in PFBR civil construction

    International Nuclear Information System (INIS)

    Civil works of PFBR has posed numerous design and construction challenges. Eight safety related nuclear buildings of PFBR are founded on a single raft, first of its kind in Indian nuclear Reactors. Construction of eight interconnected buildings on the common raft has been challenge for construction material transportation. Thus Herculean task, require storage of massive quantities of raw materials and ice. The civil construction scope in PFBR expanded to critical steel fabricated structures integrated with civil works. This includes huge embedment erected to very close tolerances. Large size panels for upper lateral, lower lateral and bottom shields were to be fabricated to intricate contours with tight tolerances and were required to be transported to locations from far off distances; this was well accomplished without loss of tolerances of fabricated structures. Novel construction practices and stringent quality control procedures were implemented to accomplish this critical requirement. Integration of cooling coils inside the safety vessel flanges after completing the reactor vault and safety vessel erection, required special contour bending for numerous reinforcement and development of special construction methodology. The neutron detector box integration with bottom shield was also a construction challenge posed and well addressed by site. Many mock ups were to be carried out for demonstrating the construction procedures and methodology for critical construction activities. Maintaining the stringent requirements such as clean room conditions was a major challenge and was met effectively. Equipment erection in parallel to civil works too required innovative solutions for clean condition maintenance while civil works are in progress. it can be said that the civil construction of PFBR has emerged as a marvel of technology handled professionally by competent engineers deploying scientific construction techniques and stringent quality control procedures. (author)

  11. EMU Challenges European Labor Markets

    OpenAIRE

    Soltwedel, Rüdiger; Dohse, Dirk; Krieger-Boden, Christiane

    1999-01-01

    This paper discusses the challenges that European Monetary Union (EMU) poses for European labor markets, emphasizing in particular the regional dimension of the European unemployment problem. The authors argue that the inability of labor markets to adjust to shocks is largely a regional problem within EMU member countries, requiring structural reforms to enhance labor market flexibility bur also a decentralization of competencies and greater diversity of labor market outcomes. Any attempt to ...

  12. PETS 2014: dataset and challenge

    OpenAIRE

    Patino, Luis; Ferryman, James

    2015-01-01

    This paper describes the dataset and vision challenges that form part of the PETS 2014 workshop. The datasets are multisensor sequences containing different activities around a parked vehicle in a parking lot. The dataset scenarios were filmed from multiple cameras mounted on the vehicle itself and involve multiple actors. In PETS2014 workshop, 22 acted scenarios are provided of abnormal behaviour around the parked vehicle. The aim in PETS 2014 is to provide a standard benchmark that indicate...

  13. Challenges in global genomics education

    Directory of Open Access Journals (Sweden)

    Ashwini de Abrew

    2014-12-01

    Full Text Available In spite of high expectations for the integration of genomics into medicine, it is not clear that health providers are competent to appropriately use new genomic approaches. The issue is further complicated by differences across the globe in terms of educational systems, access to genomic technologies, and priorities in health care. In this commentary we will review some of the major challenges in educating the health provider workforce about genomic medicine.

  14. Challenges Facing Entrepreneurship in Nigeria

    OpenAIRE

    Onyeka Uche Ofili

    2014-01-01

    Entrepreneurship is critical to the development of societies. Entrepreneurs however, cannot work in isolation; they need the right environment to thrive. The judicial system, the educational system, the financial system and generalgovernment policies should be such that encourage and promote entrepreneurship. Basic infrastructures such aspower, water, and transport systems are necessary to boost entrepreneurship. This paper looks at the challenges facing entrepreneurship in Nigeria and recomm...

  15. Statistical Challenges in Functional Genomics

    OpenAIRE

    Sebastiani, Paola; Gussoni, Emanuela; Kohane, Isaac S.; Ramoni, Marco F

    2003-01-01

    On February 12, 2001 the Human Genome Project announced the completion of a draft physical map of the human genome---the genetic blueprint for a human being. Now the challenge is to annotate this map by understanding the functions of genes and their interplay with proteins and the environment to create complex, dynamic living systems. This is the goal of functional genomics. Recent technological advances enable biomedical investigators to observe the genome of entire orga...

  16. The 5-second marketing challenge

    OpenAIRE

    Wilson, Jonathan

    2015-01-01

    Talk by: Dr Jonathan A.J. Wilson, looking at the challenges of marketing and advertising on social media - in the face of shorter attention spans and greater clutter. (Introduction by Iwan Setiwan in Bahasa Indonesia) At: the MarkPlus Inc. and KIN ASEAN Kellogg Innovation Network Annual Conference. To: an audience of 5,000 marketing delegates. In: The Ritz Carlton Pacific Place Hotel Ballroom, Jakarta, Indonesia. On: 10th December 2015. Having already delivered his confer...

  17. Challenges for Contextualizing Language Learning

    DEFF Research Database (Denmark)

    Eskildsen, Søren; Rehm, Matthias

    2013-01-01

    To help facilitate language learning for immigrants or foreigners arriving to another culture and language, we propose a context-aware mobile application. To expand on the known elements like location, activity, time and identity, we investigate the challenges on including cultural awareness to...... ensure a better experience-based learning. We present methods used to collect information about everyday activities collected by immigrants or foreigners. This information will help structuring language learning assignments presented through the context-aware mobile application....

  18. Plain language and organisational challenges

    OpenAIRE

    Pedersen, Karsten

    2014-01-01

    Changing the language in an organization is a major organizational change. In this article, I discuss some of the organizational challenges for one specific language change implementation, taking the stance that language change must be treated as any other organizational change for it to have an effect. I work with the case of the Danish tax authorities’ language project aimed at producing more readable letters. The empirical data that I work with are two qualitative informant interviews. One...

  19. Proceedings: International conference Reforestation Challenges

    OpenAIRE

    Vladan Ivetić; Dragica Stanković

    2015-01-01

    This book of Proceedings compiles 35 papers presented by researchers and scientists at The International Conference on Reforestation Challenges. Topics included various aspects of reforestation: 1) Planning and management of reforestation programs; 2) Stocktypes and seedlings quality; 3) Monitoring reforestation successes; 4) Planting and seedling-site interaction; 5) Species, intra-species and seed source selection and 6) Plant health in nurseries and plantations. In addition to country repo...

  20. Challenges of aircraft design integration

    OpenAIRE

    Kafyeke, F.; Abdo, M.; Pepin, F; Piperni, P.; Laurendeau, E.

    2007-01-01

    The design of a modern airplane brings together many disciplines: structures, aerodynamics, controls, systems, propulsion with complex interdependencies and many variables. Recent aircraft programs, such as Bombardier's Continental Jet program use participants located around the world and selected for their cost, quality and delivery capability. These participants share the risk on the program and must therefore be fully implicated in the design. A big challenge is to provide information on c...