Sample records for challenging current models

  1. Multiscale Modeling in Computational Biomechanics: Determining Computational Priorities and Addressing Current Challenges

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tawhai, Merryn; Bischoff, Jeff; Einstein, Daniel R.

    2009-05-01

    Abstract In this article, we describe some current multiscale modeling issues in computational biomechanics from the perspective of the musculoskeletal and respiratory systems and mechanotransduction. First, we outline the necessity of multiscale simulations in these biological systems. Then we summarize challenges inherent to multiscale biomechanics modeling, regardless of the subdiscipline, followed by computational challenges that are system-specific. We discuss some of the current tools that have been utilized to aid research in multiscale mechanics simulations, and the priorities to further the field of multiscale biomechanics computation.

  2. Integration of RAM-SCB into the Space Weather Modeling Framework

    DOE PAGES

    Welling, Daniel; Toth, Gabor; Jordanova, Vania Koleva; ...

    2018-02-07

    We present that numerical simulations of the ring current are a challenging endeavor. They require a large set of inputs, including electric and magnetic fields and plasma sheet fluxes. Because the ring current broadly affects the magnetosphere-ionosphere system, the input set is dependent on the ring current region itself. This makes obtaining a set of inputs that are self-consistent with the ring current difficult. To overcome this challenge, researchers have begun coupling ring current models to global models of the magnetosphere-ionosphere system. This paper describes the coupling between the Ring current Atmosphere interaction Model with Self-Consistent Magnetic field (RAM-SCB) tomore » the models within the Space Weather Modeling Framework. Full details on both previously introduced and new coupling mechanisms are defined. Finally, the impact of self-consistently including the ring current on the magnetosphere-ionosphere system is illustrated via a set of example simulations.« less

  3. Integration of RAM-SCB into the Space Weather Modeling Framework

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Welling, Daniel; Toth, Gabor; Jordanova, Vania Koleva

    We present that numerical simulations of the ring current are a challenging endeavor. They require a large set of inputs, including electric and magnetic fields and plasma sheet fluxes. Because the ring current broadly affects the magnetosphere-ionosphere system, the input set is dependent on the ring current region itself. This makes obtaining a set of inputs that are self-consistent with the ring current difficult. To overcome this challenge, researchers have begun coupling ring current models to global models of the magnetosphere-ionosphere system. This paper describes the coupling between the Ring current Atmosphere interaction Model with Self-Consistent Magnetic field (RAM-SCB) tomore » the models within the Space Weather Modeling Framework. Full details on both previously introduced and new coupling mechanisms are defined. Finally, the impact of self-consistently including the ring current on the magnetosphere-ionosphere system is illustrated via a set of example simulations.« less

  4. At the Crossroads of Nanotoxicology: Past Achievements and Current Challenges

    DTIC Science & Technology

    2015-01-01

    rates of ionic dissolution, improving in vitro to in vivo predictive efficiencies, and establishing safety exposure limits. This Review will discuss...Oberdörster et al., 2005a), which drove the focus of in vitro and in vivo model selection to accommodate these areas of higher NM exposure. Most...Accordingly, a current challenge is the design of simple, in vitro models that reliably predict in vivo effects following a NM challenge. In order

  5. Current and Future Flight Operating Systems

    NASA Technical Reports Server (NTRS)

    Cudmore, Alan

    2007-01-01

    This viewgraph presentation reviews the current real time operating system (RTOS) type in use with current flight systems. A new RTOS model is described, i.e. the process model. Included is a review of the challenges of migrating from the classic RTOS to the Process Model type.

  6. Next-Generation Climate Modeling Science Challenges for Simulation, Workflow and Analysis Systems

    NASA Astrophysics Data System (ADS)

    Koch, D. M.; Anantharaj, V. G.; Bader, D. C.; Krishnan, H.; Leung, L. R.; Ringler, T.; Taylor, M.; Wehner, M. F.; Williams, D. N.

    2016-12-01

    We will present two examples of current and future high-resolution climate-modeling research that are challenging existing simulation run-time I/O, model-data movement, storage and publishing, and analysis. In each case, we will consider lessons learned as current workflow systems are broken by these large-data science challenges, as well as strategies to repair or rebuild the systems. First we consider the science and workflow challenges to be posed by the CMIP6 multi-model HighResMIP, involving around a dozen modeling groups performing quarter-degree simulations, in 3-member ensembles for 100 years, with high-frequency (1-6 hourly) diagnostics, which is expected to generate over 4PB of data. An example of science derived from these experiments will be to study how resolution affects the ability of models to capture extreme-events such as hurricanes or atmospheric rivers. Expected methods to transfer (using parallel Globus) and analyze (using parallel "TECA" software tools) HighResMIP data for such feature-tracking by the DOE CASCADE project will be presented. A second example will be from the Accelerated Climate Modeling for Energy (ACME) project, which is currently addressing challenges involving multiple century-scale coupled high resolution (quarter-degree) climate simulations on DOE Leadership Class computers. ACME is anticipating production of over 5PB of data during the next 2 years of simulations, in order to investigate the drivers of water cycle changes, sea-level-rise, and carbon cycle evolution. The ACME workflow, from simulation to data transfer, storage, analysis and publication will be presented. Current and planned methods to accelerate the workflow, including implementing run-time diagnostics, and implementing server-side analysis to avoid moving large datasets will be presented.

  7. Next generation system modeling of NTR systems

    NASA Technical Reports Server (NTRS)

    Buksa, John J.; Rider, William J.

    1993-01-01

    The topics are presented in viewgraph form and include the following: nuclear thermal rocket (NTR) modeling challenges; current approaches; shortcomings of current analysis method; future needs; and present steps to these goals.

  8. Comparison of predictive estimates of high-latitude electrodynamics with observations of global-scale Birkeland currents

    NASA Astrophysics Data System (ADS)

    Anderson, Brian J.; Korth, Haje; Welling, Daniel T.; Merkin, Viacheslav G.; Wiltberger, Michael J.; Raeder, Joachim; Barnes, Robin J.; Waters, Colin L.; Pulkkinen, Antti A.; Rastaetter, Lutz

    2017-02-01

    Two of the geomagnetic storms for the Space Weather Prediction Center Geospace Environment Modeling challenge occurred after data were first acquired by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). We compare Birkeland currents from AMPERE with predictions from four models for the 4-5 April 2010 and 5-6 August 2011 storms. The four models are the Weimer (2005b) field-aligned current statistical model, the Lyon-Fedder-Mobarry magnetohydrodynamic (MHD) simulation, the Open Global Geospace Circulation Model MHD simulation, and the Space Weather Modeling Framework MHD simulation. The MHD simulations were run as described in Pulkkinen et al. (2013) and the results obtained from the Community Coordinated Modeling Center. The total radial Birkeland current, ITotal, and the distribution of radial current density, Jr, for all models are compared with AMPERE results. While the total currents are well correlated, the quantitative agreement varies considerably. The Jr distributions reveal discrepancies between the models and observations related to the latitude distribution, morphologies, and lack of nightside current systems in the models. The results motivate enhancing the simulations first by increasing the simulation resolution and then by examining the relative merits of implementing more sophisticated ionospheric conductance models, including ionospheric outflows or other omitted physical processes. Some aspects of the system, including substorm timing and location, may remain challenging to simulate, implying a continuing need for real-time specification.

  9. Current Status and Challenges of Atmospheric Data Assimilation

    NASA Astrophysics Data System (ADS)

    Atlas, R. M.; Gelaro, R.

    2016-12-01

    The issues of modern atmospheric data assimilation are fairly simple to comprehend but difficult to address, involving the combination of literally billions of model variables and tens of millions of observations daily. In addition to traditional meteorological variables such as wind, temperature pressure and humidity, model state vectors are being expanded to include explicit representation of precipitation, clouds, aerosols and atmospheric trace gases. At the same time, model resolutions are approaching single-kilometer scales globally and new observation types have error characteristics that are increasingly non-Gaussian. This talk describes the current status and challenges of atmospheric data assimilation, including an overview of current methodologies, the difficulty of estimating error statistics, and progress toward coupled earth system analyses.

  10. Ahead of the Curve: Implementation Challenges in Personalized Learning School Models

    ERIC Educational Resources Information Center

    Bingham, Andrea J.; Pane, John F.; Steiner, Elizabeth D.; Hamilton, Laura S.

    2018-01-01

    In the current educational context, school models that leverage technology to personalize instruction have proliferated, as has student enrollment in, and funding of, such school models. However, even the best laid plans are subject to challenges in design and practice, particularly in the dynamic context of a school. In this collective case…

  11. Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges

    PubMed Central

    Day, Chi-Ping; Merlino, Glenn; Van Dyke, Terry

    2015-01-01

    Significant advances have been made in developing novel therapeutics for cancer treatment, and targeted therapies have revolutionized the treatment of some cancers. Despite the promise, only about five percent of new cancer drugs are approved, and most fail due to lack of efficacy. The indication is that current preclinical methods are limited in predicting successful outcomes. Such failure exacts enormous cost, both financial and in the quality of human life. This primer explores the current status, promise and challenges of preclinical evaluation in advanced mouse cancer models and briefly addresses emerging models for early-stage preclinical development. PMID:26406370

  12. Challenges to Apprenticeship Learning in Religious Education: Narrow Use of the Apprenticeship Model and Current Developments in Youth Ministry

    ERIC Educational Resources Information Center

    de Kock, A.

    2017-01-01

    In 2012, I proposed the apprenticeship model as a promising catechetical model for church communities in which catechists might be hope generators, and the church community becomes a community of hope. This article argues that the original meaning of the apprenticeship model is challenged by an emphasis in youth ministry practices on the…

  13. Dst Index in the 2008 GEM Modeling Challenge - Model Performance for Moderate and Strong Magnetic Storms

    NASA Technical Reports Server (NTRS)

    Rastaetter, Lutz; Kuznetsova, Maria; Hesse, Michael; Chulaki, Anna; Pulkkinen, Antti; Ridley, Aaron J.; Gombosi, Tamas; Vapirev, Alexander; Raeder, Joachim; Wiltberger, Michael James; hide

    2010-01-01

    The GEM 2008 modeling challenge efforts are expanding beyond comparing in-situ measurements in the magnetosphere and ionosphere to include the computation of indices to be compared. The Dst index measures the largest deviations of the horizontal magnetic field at 4 equatorial magnetometers from the quiet-time background field and is commonly used to track the strength of the magnetic disturbance of the magnetosphere during storms. Models can calculate a proxy Dst index in various ways, including using the Dessler-Parker Sckopke relation and the energy of the ring current and Biot-Savart integration of electric currents in the magnetosphere. The GEM modeling challenge investigates 4 space weather events and we compare models available at CCMC against each other and the observed values of Ost. Models used include SWMF/BATSRUS, OpenGGCM, LFM, GUMICS (3D magnetosphere MHD models), Fok-RC, CRCM, RAM-SCB (kinetic drift models of the ring current), WINDMI (magnetosphere-ionosphere electric circuit model), and predictions based on an impulse response function (IRF) model and analytic coupling functions with inputs of solar wind data. In addition to the analysis of model-observation comparisons we look at the way Dst is computed in global magnetosphere models. The default value of Dst computed by the SWMF model is for Bz the Earth's center. In addition to this, we present results obtained at different locations on the Earth's surface. We choose equatorial locations at local noon, dusk (18:00 hours), midnight and dawn (6:00 hours). The different virtual observatory locations reveal the variation around the earth-centered Dst value resulting from the distribution of electric currents in the magnetosphere during different phases of a storm.

  14. Geospace environment modeling 2008--2009 challenge: Dst index

    USGS Publications Warehouse

    Rastätter, L.; Kuznetsova, M.M.; Glocer, A.; Welling, D.; Meng, X.; Raeder, J.; Wittberger, M.; Jordanova, V.K.; Yu, Y.; Zaharia, S.; Weigel, R.S.; Sazykin, S.; Boynton, R.; Wei, H.; Eccles, V.; Horton, W.; Mays, M.L.; Gannon, J.

    2013-01-01

    This paper reports the metrics-based results of the Dst index part of the 2008–2009 GEM Metrics Challenge. The 2008–2009 GEM Metrics Challenge asked modelers to submit results for four geomagnetic storm events and five different types of observations that can be modeled by statistical, climatological or physics-based models of the magnetosphere-ionosphere system. We present the results of 30 model settings that were run at the Community Coordinated Modeling Center and at the institutions of various modelers for these events. To measure the performance of each of the models against the observations, we use comparisons of 1 hour averaged model data with the Dst index issued by the World Data Center for Geomagnetism, Kyoto, Japan, and direct comparison of 1 minute model data with the 1 minute Dst index calculated by the United States Geological Survey. The latter index can be used to calculate spectral variability of model outputs in comparison to the index. We find that model rankings vary widely by skill score used. None of the models consistently perform best for all events. We find that empirical models perform well in general. Magnetohydrodynamics-based models of the global magnetosphere with inner magnetosphere physics (ring current model) included and stand-alone ring current models with properly defined boundary conditions perform well and are able to match or surpass results from empirical models. Unlike in similar studies, the statistical models used in this study found their challenge in the weakest events rather than the strongest events.

  15. Computational challenges in modeling gene regulatory events.

    PubMed

    Pataskar, Abhijeet; Tiwari, Vijay K

    2016-10-19

    Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

  16. State and transition models: Theory, applications, and challenges. In: Briske, D.D. Rangeland Systems: Processes, Management and Challenges

    USDA-ARS?s Scientific Manuscript database

    State and transition models (STMs) are used for communicating about ecosystem change in rangelands and other ecosystems, especially the implications for management. The fundamental premise that rangelands can exhibit multiple states is now widely accepted. The current application of STMs for managem...

  17. Ocean Modeling and Visualization on Massively Parallel Computer

    NASA Technical Reports Server (NTRS)

    Chao, Yi; Li, P. Peggy; Wang, Ping; Katz, Daniel S.; Cheng, Benny N.

    1997-01-01

    Climate modeling is one of the grand challenges of computational science, and ocean modeling plays an important role in both understanding the current climatic conditions and predicting future climate change.

  18. Current Status and Future Challenges in Risk-Based Radiation Engineering

    NASA Technical Reports Server (NTRS)

    Pellish, Jonathan A.

    2017-01-01

    This presentation covers the basis and challenges for radiation effects in electronic systems. The three main types of radiation effects in electronics are: 1) total ionizing dose (TID), 2) total non-ionizing dose (TNID) / displacement damage dose (DDD), and 3) single-event effect (SEE). Some content on relevant examples of effects, current concerns, and possible environmental model-driven solutions are also included.

  19. Computational challenges in modeling gene regulatory events

    PubMed Central

    Pataskar, Abhijeet; Tiwari, Vijay K.

    2016-01-01

    ABSTRACT Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating “omics” data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology. PMID:27390891

  20. Additive and Interactive Effects of Stimulus Degradation: No Challenge for CDP+

    ERIC Educational Resources Information Center

    Ziegler, Johannes C.; Perry, Conrad; Zorzi, Marco

    2009-01-01

    S. O'Malley and D. Besner (2008) showed that additive effects of stimulus degradation and word frequency in reading aloud occur in the presence of nonwords but not in pure word lists. They argued that this dissociation presents a major challenge to interactive computational models of reading aloud and claimed that no currently implemented model is…

  1. A Meta-Analysis of Video-Modeling Based Interventions for Reduction of Challenging Behaviors for Students with EBD

    ERIC Educational Resources Information Center

    Losinski, Mickey; Wiseman, Nicole; White, Sherry A.; Balluch, Felicity

    2016-01-01

    The current study examined the use of video modeling (VM)-based interventions to reduce the challenging behaviors of students with emotional or behavioral disorders. Each study was evaluated using Council for Exceptional Children's (CEC's) quality indicators for evidence-based practices. In addition, study effects were calculated along the three…

  2. Climate Ocean Modeling on Parallel Computers

    NASA Technical Reports Server (NTRS)

    Wang, P.; Cheng, B. N.; Chao, Y.

    1998-01-01

    Ocean modeling plays an important role in both understanding the current climatic conditions and predicting future climate change. However, modeling the ocean circulation at various spatial and temporal scales is a very challenging computational task.

  3. Staying Connected: Sustaining Collaborative Care Models with Limited Funding.

    PubMed

    Johnston, Brenda J; Peppard, Lora; Newton, Marian

    2015-08-01

    Providing psychiatric services in the primary care setting is challenging. The multidisciplinary, coordinated approach of collaborative care models (CCMs) addresses these challenges. The purpose of the current article is to discuss the implementation of a CCM at a free medical clinic (FMC) where volunteer staff provide the majority of services. Essential components of CCMs include (a) comprehensive screening and assessment, (b) shared development and communication of care plans among providers and the patient, and (c) care coordination and management. Challenges to implementing and sustaining a CCM at a FMC in Virginia attempting to meet the medical and psychiatric needs of the underserved are addressed. Although the CCM produced favorable outcomes, sustaining the model long-term presented many challenges. Strategies for addressing these challenges are discussed. Copyright 2015, SLACK Incorporated.

  4. A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine: towards implementing patient-level models.

    PubMed

    Degeling, Koen; Koffijberg, Hendrik; IJzerman, Maarten J

    2017-02-01

    The ongoing development of genomic medicine and the use of molecular and imaging markers in personalized medicine (PM) has arguably challenged the field of health economic modeling (HEM). This study aims to provide detailed insights into the current status of HEM in PM, in order to identify if and how modeling methods are used to address the challenges described in literature. Areas covered: A review was performed on studies that simulate health economic outcomes for personalized clinical pathways. Decision tree modeling and Markov modeling were the most observed methods. Not all identified challenges were frequently found, challenges regarding companion diagnostics, diagnostic performance, and evidence gaps were most often found. However, the extent to which challenges were addressed varied considerably between studies. Expert commentary: Challenges for HEM in PM are not yet routinely addressed which may indicate that either (1) their impact is less severe than expected, (2) they are hard to address and therefore not managed appropriately, or (3) HEM in PM is still in an early stage. As evidence on the impact of these challenges is still lacking, we believe that more concrete examples are needed to illustrate the identified challenges and to demonstrate methods to handle them.

  5. A New Framework for Massive Open Online Courses (MOOCs)

    ERIC Educational Resources Information Center

    Schoenack, Lindsie

    2013-01-01

    The challenges that massive open online courses (MOOCs) bring to the learning arena spur adult educators to improve delivery. A framework for a new type of MOOC is presented to address some of the challenges presented by earlier models. This new MOOC, called a mesoMOOC, can bridge several challenges that hinder current effective delivery of MOOCs…

  6. Modeling of Photoionized Plasmas

    NASA Technical Reports Server (NTRS)

    Kallman, Timothy R.

    2010-01-01

    In this paper I review the motivation and current status of modeling of plasmas exposed to strong radiation fields, as it applies to the study of cosmic X-ray sources. This includes some of the astrophysical issues which can be addressed, the ingredients for the models, the current computational tools, the limitations imposed by currently available atomic data, and the validity of some of the standard assumptions. I will also discuss ideas for the future: challenges associated with future missions, opportunities presented by improved computers, and goals for atomic data collection.

  7. Developing Learning Environments: Challenges for Theory, Research and Practice.

    ERIC Educational Resources Information Center

    Iles, Paul

    1994-01-01

    Key challenges in development of learning organizations, promotion of learning culture, enhancement of learning processes, and development of learning communities are appropriateness of current models for interdisciplinary teams; whether valuing diversity enhances effectiveness; how global human resource development affects domestic; and what…

  8. Current status of deepwater oil spill modelling in the Faroe-Shetland Channel, Northeast Atlantic, and future challenges.

    PubMed

    Gallego, Alejandro; O'Hara Murray, Rory; Berx, Barbara; Turrell, William R; Beegle-Krause, C J; Inall, Mark; Sherwin, Toby; Siddorn, John; Wakelin, Sarah; Vlasenko, Vasyl; Hole, Lars R; Dagestad, Knut Frode; Rees, John; Short, Lucy; Rønningen, Petter; Main, Charlotte E; Legrand, Sebastien; Gutierrez, Tony; Witte, Ursula; Mulanaphy, Nicole

    2018-02-01

    As oil reserves in established basins become depleted, exploration and production moves towards relatively unexploited areas, such as deep waters off the continental shelf. The Faroe-Shetland Channel (FSC, NE Atlantic) and adjacent areas have been subject to increased focus by the oil industry. In addition to extreme depths, metocean conditions in this region characterise an environment with high waves and strong winds, strong currents, complex circulation patterns, sharp density gradients, and large small- and mesoscale variability. These conditions pose operational challenges to oil spill response and question the suitability of current oil spill modelling frameworks (oil spill models and their forcing data) to adequately simulate the behaviour of a potential oil spill in the area. This article reviews the state of knowledge relevant to deepwater oil spill modelling for the FSC area and identifies knowledge gaps and research priorities. Our analysis should be relevant to other areas of complex oceanography. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  9. WFIRST: Exoplanet Data Challenge. Atmospheric retrieval results

    NASA Astrophysics Data System (ADS)

    Hildebrandt, Sergi; Turnbull, Margaret; Exoplanet Data Challenge Team

    2018-01-01

    We present the results of the Exoplanet Data Challenge for its first 2016/17 cycle and the current cycle 2. Some input spectra for extra-solar systems are processed through the WFIRST IFS instrument model, producing simulated data representative of the flight data. Atmospheric properties are then recovered using complex atmospheric models and multidimensional optimization. The results inform about WFIRST CGI ability to characterize exo-planetray atmospheres.

  10. ACTDs: Management Plans as Predictors of Transition

    DTIC Science & Technology

    2007-12-01

    phase. Figure 2 shows the current ACTD funding model in place today and highlights the challenges involved in the process. Current ACTD Funding ... Model All other Sources (~70%) OSD AS&C Cash Resources (~30%) Army PE x PE x PE x PE x Navy PE x PE x PE x PE x USAF PE x PE x

  11. Technology Transfer Challenges for High-Assurance Software Engineering Tools

    NASA Technical Reports Server (NTRS)

    Koga, Dennis (Technical Monitor); Penix, John; Markosian, Lawrence Z.

    2003-01-01

    In this paper, we describe our experience with the challenges thar we are currently facing in our effort to develop advanced software verification and validation tools. We categorize these challenges into several areas: cost benefits modeling, tool usability, customer application domain, and organizational issues. We provide examples of challenges in each area and identrfj, open research issues in areas which limit our ability to transfer high-assurance software engineering tools into practice.

  12. Coarse Grained Model for Biological Simulations: Recent Refinements and Validation

    PubMed Central

    Vicatos, Spyridon; Rychkova, Anna; Mukherjee, Shayantani; Warshel, Arieh

    2014-01-01

    Exploring the free energy landscape of proteins and modeling the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of various simplified coarse grained (CG) models offers an effective way of sampling the landscape, but most current models are not expected to give a reliable description of protein stability and functional aspects. The main problem is associated with insufficient focus on the electrostatic features of the model. In this respect our recent CG model offers significant advantage as it has been refined while focusing on its electrostatic free energy. Here we review the current state of our model, describing recent refinement, extensions and validation studies while focusing on demonstrating key applications. These include studies of protein stability, extending the model to include membranes and electrolytes and electrodes as well as studies of voltage activated proteins, protein insertion trough the translocon, the action of molecular motors and even the coupling of the stalled ribosome and the translocon. Our example illustrates the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins and large macromolecular complexes. PMID:25050439

  13. Summary of "Using Student Growth to Evaluate Educators of Students with Disabilities: Issues, Challenges, and Next Steps": A Forum of State Special Education and Teacher Effectiveness Experts and Researchers. Forum Summary

    ERIC Educational Resources Information Center

    Holdheide, Lynn; Browder, Diane; Warren, Sandra; Buzick, Heather; Jones, Nathan

    2012-01-01

    With the current emphasis in educational policy on improving teacher effectiveness, states and school districts are quickly developing and implementing new models of teacher evaluation. However, few models address the unique challenges in accurately measuring achievement growth of students with disabilities (including those participating in…

  14. Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases

    PubMed Central

    Amos, Christopher I.; Bafna, Vineet; Hauser, Elizabeth R.; Hernandez, Ryan D.; Li, Chun; Liberles, David A.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Papanicolaou, George J.; Peng, Bo; Ritchie, Marylyn D.; Rosenfeld, Gabriel; Witte, John S.

    2014-01-01

    Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high-throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled “Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases” at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were to: (i) identify opportunities, challenges and resource needs for the development and application of genetic simulation models; (ii) improve the integration of tools for modeling and analysis of simulated data; and (iii) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation. PMID:25371374

  15. Application of soft computing based hybrid models in hydrological variables modeling: a comprehensive review

    NASA Astrophysics Data System (ADS)

    Fahimi, Farzad; Yaseen, Zaher Mundher; El-shafie, Ahmed

    2017-05-01

    Since the middle of the twentieth century, artificial intelligence (AI) models have been used widely in engineering and science problems. Water resource variable modeling and prediction are the most challenging issues in water engineering. Artificial neural network (ANN) is a common approach used to tackle this problem by using viable and efficient models. Numerous ANN models have been successfully developed to achieve more accurate results. In the current review, different ANN models in water resource applications and hydrological variable predictions are reviewed and outlined. In addition, recent hybrid models and their structures, input preprocessing, and optimization techniques are discussed and the results are compared with similar previous studies. Moreover, to achieve a comprehensive view of the literature, many articles that applied ANN models together with other techniques are included. Consequently, coupling procedure, model evaluation, and performance comparison of hybrid models with conventional ANN models are assessed, as well as, taxonomy and hybrid ANN models structures. Finally, current challenges and recommendations for future researches are indicated and new hybrid approaches are proposed.

  16. Current Challenges in the First Principle Quantitative Modelling of the Lower Hybrid Current Drive in Tokamaks

    NASA Astrophysics Data System (ADS)

    Peysson, Y.; Bonoli, P. T.; Chen, J.; Garofalo, A.; Hillairet, J.; Li, M.; Qian, J.; Shiraiwa, S.; Decker, J.; Ding, B. J.; Ekedahl, A.; Goniche, M.; Zhai, X.

    2017-10-01

    The Lower Hybrid (LH) wave is widely used in existing tokamaks for tailoring current density profile or extending pulse duration to steady-state regimes. Its high efficiency makes it particularly attractive for a fusion reactor, leading to consider it for this purpose in ITER tokamak. Nevertheless, if basics of the LH wave in tokamak plasma are well known, quantitative modeling of experimental observations based on first principles remains a highly challenging exercise, despite considerable numerical efforts achieved so far. In this context, a rigorous methodology must be carried out in the simulations to identify the minimum number of physical mechanisms that must be considered to reproduce experimental shot to shot observations and also scalings (density, power spectrum). Based on recent simulations carried out for EAST, Alcator C-Mod and Tore Supra tokamaks, the state of the art in LH modeling is reviewed. The capability of fast electron bremsstrahlung, internal inductance li and LH driven current at zero loop voltage to constrain all together LH simulations is discussed, as well as the needs of further improvements (diagnostics, codes, LH model), for robust interpretative and predictive simulations.

  17. The mathematics of cancer: integrating quantitative models.

    PubMed

    Altrock, Philipp M; Liu, Lin L; Michor, Franziska

    2015-12-01

    Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

  18. Challenges in the global QCD analysis of parton structure of nucleons

    NASA Astrophysics Data System (ADS)

    Tung, Wu-Ki

    2000-12-01

    We briefly summarize the current status of global QCD analysis of the parton structure of the nucleon and then highlight the open questions and challenges which confront this endeavor on which much of the phenomenology of the Standard Model and the search of New Physics depend.

  19. Effects of Horticulture Therapy on Engagement and Affect

    ERIC Educational Resources Information Center

    Gigliotti, Christina M.; Jarrott, Shannon E.

    2005-01-01

    Implementing generationally appropriate activities for persons with dementia is a challenging task. Horticulture therapy (HT) addresses this challenge through the use of plants to facilitate holistic outcomes. Utilizing the model of environmental press, the current study sought to analyse adult day service (ADS) participants' responses to HT as…

  20. Facing the challenges of multiscale modelling of bacterial and fungal pathogen–host interactions

    PubMed Central

    Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard

    2017-01-01

    Abstract Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host–pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. PMID:26857943

  1. Seven challenges for modelling indirect transmission: Vector-borne diseases, macroparasites and neglected tropical diseases

    PubMed Central

    Hollingsworth, T. Déirdre; Pulliam, Juliet R.C.; Funk, Sebastian; Truscott, James E.; Isham, Valerie; Lloyd, Alun L.

    2015-01-01

    Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission – whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of “evolution-proof” interventions against vector-borne disease. PMID:25843376

  2. Seven challenges for modelling indirect transmission: vector-borne diseases, macroparasites and neglected tropical diseases.

    PubMed

    Hollingsworth, T Déirdre; Pulliam, Juliet R C; Funk, Sebastian; Truscott, James E; Isham, Valerie; Lloyd, Alun L

    2015-03-01

    Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission--whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of "evolution-proof" interventions against vector-borne disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Computational Aeroelastic Modeling of Airframes and TurboMachinery: Progress and Challenges

    NASA Technical Reports Server (NTRS)

    Bartels, R. E.; Sayma, A. I.

    2006-01-01

    Computational analyses such as computational fluid dynamics and computational structural dynamics have made major advances toward maturity as engineering tools. Computational aeroelasticity is the integration of these disciplines. As computational aeroelasticity matures it too finds an increasing role in the design and analysis of aerospace vehicles. This paper presents a survey of the current state of computational aeroelasticity with a discussion of recent research, success and continuing challenges in its progressive integration into multidisciplinary aerospace design. This paper approaches computational aeroelasticity from the perspective of the two main areas of application: airframe and turbomachinery design. An overview will be presented of the different prediction methods used for each field of application. Differing levels of nonlinear modeling will be discussed with insight into accuracy versus complexity and computational requirements. Subjects will include current advanced methods (linear and nonlinear), nonlinear flow models, use of order reduction techniques and future trends in incorporating structural nonlinearity. Examples in which computational aeroelasticity is currently being integrated into the design of airframes and turbomachinery will be presented.

  4. Protective effects of vaccines against Bordetella parapertussis in a mouse intranasal challenge model.

    PubMed

    Komatsu, Eiji; Yamaguchi, Fuminori; Eguchi, Masahiro; Watanabe, Mineo

    2010-06-17

    Bordetella parapertussis causes typical whooping cough, as does Bordetella pertussis. However, current commercial vaccines are ineffective against B. parapertussis. In an effort to develop vaccines that are effective in protecting against both B. pertussis and B. parapertussis, we examined the protective effects of vaccines prepared from whole-cells and from recombinant proteins derived from B. parapertussis in a mouse intranasal challenge model. We confirmed current pertussis vaccines did not induce protective immunity against B. parapertussis in the mouse model. A whole-cell vaccine prepared from B. parapertussis induced protective immunity against B. parapertussis but not against B. pertussis, suggesting a combination of a current pertussis vaccine with a whole-cell parapertussis vaccine might prevent whooping cough caused by both species of Bordetella. We also found that filamentous hemagglutinin was a protective antigen of B. parapertussis. Our observations should lead to the development of new pertussis vaccines that can control the two prevalent forms of whooping cough.

  5. Exemplar for simulation challenges: Large-deformation micromechanics of Sylgard 184/glass microballoon syntactic foams.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, Judith Alice; Long, Kevin Nicholas

    2018-05-01

    Sylgard® 184/Glass Microballoon (GMB) potting material is currently used in many NW systems. Analysts need a macroscale constitutive model that can predict material behavior under complex loading and damage evolution. To address this need, ongoing modeling and experimental efforts have focused on study of damage evolution in these materials. Micromechanical finite element simulations that resolve individual GMB and matrix components promote discovery and better understanding of the material behavior. With these simulations, we can study the role of the GMB volume fraction, time-dependent damage, behavior under confined vs. unconfined compression, and the effects of partial damage. These simulations are challengingmore » and push the boundaries of capability even with the high performance computing tools available at Sandia. We summarize the major challenges and the current state of this modeling effort, as an exemplar of micromechanical modeling needs that can motivate advances in future computing efforts.« less

  6. Practical examples of modeling choices and their consequences for risk assessment

    EPA Science Inventory

    Although benchmark dose (BMD) modeling has become the preferred approach to identifying a point of departure (POD) over the No Observed Adverse Effect Level, there remain challenges to its application in human health risk assessment. BMD modeling, as currently implemented by the...

  7. Physics-based distributed snow models in the operational arena: Current and future challenges

    NASA Astrophysics Data System (ADS)

    Winstral, A. H.; Jonas, T.; Schirmer, M.; Helbig, N.

    2017-12-01

    The demand for modeling tools robust to climate change and weather extremes along with coincident increases in computational capabilities have led to an increase in the use of physics-based snow models in operational applications. Current operational applications include the WSL-SLF's across Switzerland, ASO's in California, and USDA-ARS's in Idaho. While the physics-based approaches offer many advantages there remain limitations and modeling challenges. The most evident limitation remains computation times that often limit forecasters to a single, deterministic model run. Other limitations however remain less conspicuous amidst the assumptions that these models require little to no calibration based on their foundation on physical principles. Yet all energy balance snow models seemingly contain parameterizations or simplifications of processes where validation data are scarce or present understanding is limited. At the research-basin scale where many of these models were developed these modeling elements may prove adequate. However when applied over large areas, spatially invariable parameterizations of snow albedo, roughness lengths and atmospheric exchange coefficients - all vital to determining the snowcover energy balance - become problematic. Moreover as we apply models over larger grid cells, the representation of sub-grid variability such as the snow-covered fraction adds to the challenges. Here, we will demonstrate some of the major sensitivities of distributed energy balance snow models to particular model constructs, the need for advanced and spatially flexible methods and parameterizations, and prompt the community for open dialogue and future collaborations to further modeling capabilities.

  8. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

    PubMed Central

    McGreevy, Joe W.; Hakim, Chady H.; McIntosh, Mark A.; Duan, Dongsheng

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. PMID:25740330

  9. The robust nature of the biopsychosocial model challenge and threat: a reply to Wright and Kirby.

    PubMed

    Blascovich, Jim; Mendes, Wendy Berry; Tomaka, Joe; Salomon, Kristen; Seery, Mark

    2003-01-01

    This article responds to Wright and Kirby's (this issue) critique of our biopsychosocial (BPS) analysis of challenge and threat motivation. We counter their arguments by reviewing the current state of our theory as well as supporting data, then turn to their specific criticisms. We believe that Wright and Kirby failed to accurately represent the corpus of our work, including both our theoretical model and its supporting data. They critiqued our model from a contextual, rational-economic perspective that ignores the complexity and subjectivity of person-person and person-environmental interactions as well as nonconscious influences. Finally, they provided criticisms regarding possible underspecificity of antecedent components of our model that do not so much indicate theoretical flaws as provide important and interesting questions for future research. We conclude by affirming that our BPS model of challenge and threat is an evolving, generative theory directed toward understanding the complexity of personality and social psychological factors underlying challenge and threat states.

  10. Redefining success as significance through leadership in the new economy.

    PubMed

    De Jong, Steven A

    2006-03-01

    This review re-examines our current definition of success in the current economic system and challenges the surgeon to play a significant part in role modeling and mentoring surgical residents and other healthcare professionals. Leadership skills are presented and implementation strategies are suggested.

  11. From California dreaming to California data: Challenging historic models for landfill CH4 emissions

    USDA-ARS?s Scientific Manuscript database

    Improved quantification of diverse CH4 sources at the urban scale is needed to guide local greenhouse gas (GHG) mitigation strategies in the Anthropocene. Herein, we focus on landfill CH4 emissions in California, challenging the current IPCC methodology which focuses on a climate dependency for land...

  12. 2008 GEM Modeling Challenge: Metrics Study of the Dst Index in Physics-Based Magnetosphere and Ring Current Models and in Statistical and Analytic Specifications

    NASA Technical Reports Server (NTRS)

    Rastaetter, L.; Kuznetsova, M.; Hesse, M.; Pulkkinen, A.; Glocer, A.; Yu, Y.; Meng, X.; Raeder, J.; Wiltberger, M.; Welling, D.; hide

    2011-01-01

    In this paper the metrics-based results of the Dst part of the 2008-2009 GEM Metrics Challenge are reported. The Metrics Challenge asked modelers to submit results for 4 geomagnetic storm events and 5 different types of observations that can be modeled by statistical or climatological or physics-based (e.g. MHD) models of the magnetosphere-ionosphere system. We present the results of over 25 model settings that were run at the Community Coordinated Modeling Center (CCMC) and at the institutions of various modelers for these events. To measure the performance of each of the models against the observations we use comparisons of one-hour averaged model data with the Dst index issued by the World Data Center for Geomagnetism, Kyoto, Japan, and direct comparison of one-minute model data with the one-minute Dst index calculated by the United States Geologic Survey (USGS).

  13. Model Uncertainty and Bayesian Model Averaged Benchmark Dose Estimation for Continuous Data

    EPA Science Inventory

    The benchmark dose (BMD) approach has gained acceptance as a valuable risk assessment tool, but risk assessors still face significant challenges associated with selecting an appropriate BMD/BMDL estimate from the results of a set of acceptable dose-response models. Current approa...

  14. MULTIVARIATE RECEPTOR MODELS-CURRENT PRACTICE AND FUTURE TRENDS. (R826238)

    EPA Science Inventory

    Multivariate receptor models have been applied to the analysis of air quality data for sometime. However, solving the general mixture problem is important in several other fields. This paper looks at the panoply of these models with a view of identifying common challenges and ...

  15. Why learning and development can lead to poorer recognition memory.

    PubMed

    Hayes, Brett K; Heit, Evan

    2004-08-01

    Current models of inductive reasoning in children and adults assume a central role for categorical knowledge. A recent paper by Sloutsky and Fisher challenges this assumption, showing that children are more likely than adults to rely on perceptual similarity as a basis for induction, and introduces a more direct method for examining the representations activated during induction. This method has the potential to constrain models of induction in novel ways, although there are still important challenges.

  16. Examining the Links between Challenging Behaviors in Youth with ASD and Parental Stress, Mental Health, and Involvement: Applying an Adaptation of the Family Stress Model to Families of Youth with ASD

    ERIC Educational Resources Information Center

    Schiltz, Hillary K.; McVey, Alana J.; Magnus, Brooke; Dolan, Bridget K.; Willar, Kirsten S.; Pleiss, Sheryl; Karst, Jeffrey; Carson, Audrey M.; Caiozzo, Christina; Vogt, Elisabeth; Van Hecke, Amy Vaughan

    2018-01-01

    Raising a child with autism spectrum disorder (ASD) poses unique challenges that may impact parents' mental health and parenting experiences. The current study analyzed self-report data from 77 parents of youth with ASD. A serial multiple mediation model revealed that parenting stress (SIPA) and parental mental health (BAI and BDI-II) appears to…

  17. The physicochemical process of bacterial attachment to abiotic surfaces: Challenges for mechanistic studies, predictability and the development of control strategies.

    PubMed

    Wang, Yi; Lee, Sui Mae; Dykes, Gary

    2015-01-01

    Bacterial attachment to abiotic surfaces can be explained as a physicochemical process. Mechanisms of the process have been widely studied but are not yet well understood due to their complexity. Physicochemical processes can be influenced by various interactions and factors in attachment systems, including, but not limited to, hydrophobic interactions, electrostatic interactions and substratum surface roughness. Mechanistic models and control strategies for bacterial attachment to abiotic surfaces have been established based on the current understanding of the attachment process and the interactions involved. Due to a lack of process control and standardization in the methodologies used to study the mechanisms of bacterial attachment, however, various challenges are apparent in the development of models and control strategies. In this review, the physicochemical mechanisms, interactions and factors affecting the process of bacterial attachment to abiotic surfaces are described. Mechanistic models established based on these parameters are discussed in terms of their limitations. Currently employed methods to study these parameters and bacterial attachment are critically compared. The roles of these parameters in the development of control strategies for bacterial attachment are reviewed, and the challenges that arise in developing mechanistic models and control strategies are assessed.

  18. Social Work Education on Mental Health: Postmodern Discourse and the Medical Model

    ERIC Educational Resources Information Center

    Casstevens, W. J.

    2010-01-01

    This article provides a pedagogical approach to presenting alternatives along with the traditional medical model in the context of mental health treatment and service provision. Given the current influence of the medical model in community mental health, this article outlines a rationale for challenging the model and considering alternative models…

  19. The trials and tribulations of a practitioner-researcher: challenges and lessons learned through testing a feminist-cognitive-relational social work model of practice.

    PubMed

    Dombo, Eileen A; Bass, Ami P

    2014-01-01

    In practice with adult women who survived childhood sexual abuse, the field of social work currently lacks an evidence-based intervention. The current interventions, from the 1990s, come primarily from psychologists. The hypothesis that the Feminist-Cognitive-Relational Social Work Model and Intervention will be more effective in decreasing cognitive distortions, and increasing intimacy and relational health when compared to the standard agency intervention was tested in a quasi-experimental study. The challenges in carrying out the study in small, non-profit organizations are explored to highlight the difficulties in developing evidence-based interventions. Changes to implementation that resulted from the research findings are discussed.

  20. Fusing visual and behavioral cues for modeling user experience in games.

    PubMed

    Shaker, Noor; Asteriadis, Stylianos; Yannakakis, Georgios N; Karpouzis, Kostas

    2013-12-01

    Estimating affective and cognitive states in conditions of rich human-computer interaction, such as in games, is a field of growing academic and commercial interest. Entertainment and serious games can benefit from recent advances in the field as, having access to predictors of the current state of the player (or learner) can provide useful information for feeding adaptation mechanisms that aim to maximize engagement or learning effects. In this paper, we introduce a large data corpus derived from 58 participants that play the popular Super Mario Bros platform game and attempt to create accurate models of player experience for this game genre. Within the view of the current research, features extracted both from player gameplay behavior and game levels, and player visual characteristics have been used as potential indicators of reported affect expressed as pairwise preferences between different game sessions. Using neuroevolutionary preference learning and automatic feature selection, highly accurate models of reported engagement, frustration, and challenge are constructed (model accuracies reach 91%, 92%, and 88% for engagement, frustration, and challenge, respectively). As a step further, the derived player experience models can be used to personalize the game level to desired levels of engagement, frustration, and challenge as game content is mapped to player experience through the behavioral and expressivity patterns of each player.

  1. Why the elderly could bankrupt Canada and how demographic imperatives will force the redesign of acute care service delivery.

    PubMed

    Sinha, Samir K

    2011-01-01

    Canada's aging population poses a significant challenge for the existing healthcare system. While individuals 65 and older accounted for 13.7% of the population in 2005, they accounted for 60% of all acute care service spending. This paper further illustrates how the heterogeneity of the older population and its impact on patterns of healthcare use demonstrate the failings of our current care systems. Our outdated acute care models frequently disadvantage the system's highest users, who are often characterized by factors such as poly-morbidity, functional impairment and social frailty. Understanding how implementing innovative models that challenge deeply ingrained ways of providing care has proven to be a significant challenge, this paper highlights one hospital's mission to transform current traditional paradigms of care by developing and implementing an elder-friendly hospital integrated service delivery model. This hospital aims to demonstrate wide-ranging benefits of this model that can contribute toward optimizing the outcomes of hospitalization for older adults and the system as a whole. The establishment of a national agency that could support the development of a national aging strategy to promote best practice dissemination and implementation could also ensure that the significant health, social and economic benefits that better care models can realize could be more easily achieved.

  2. Usability and accessibility in consumer health informatics current trends and future challenges.

    PubMed

    Goldberg, Larry; Lide, Bettijoyce; Lowry, Svetlana; Massett, Holly A; O'Connell, Trisha; Preece, Jennifer; Quesenbery, Whitney; Shneiderman, Ben

    2011-05-01

    It is a truism that, for innovative eHealth systems to have true value and impact, they must first and foremost be usable and accessible by clinicians, consumers, and other stakeholders. In this paper, current trends and future challenges in the usability and accessibility of consumer health informatics will be described. Consumer expectations of their healthcare providers and healthcare records in this new era of consumer-directed care will be explored, and innovative visualizations, assistive technologies, and other ways that healthcare information is currently being provided and/or shared will be described. Challenges for ensuring the usability of current and future systems will also be discussed. An innovative model for conducting systematic, timely, user-centered research on consumer-facing websites at the National Cancer Institute (NCI) and the ongoing efforts at the National Institute of Standards and Technology (NIST) to promote health information technology (HIT) usability standards and evaluation criteria will also be presented. Copyright © 2011 American Journal of Preventive Medicine. All rights reserved.

  3. Data needs for X-ray astronomy satellites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kallman, T.

    I review the current status of atomic data for X-ray astronomy satellites. This includes some of the astrophysical issues which can be addressed, current modeling and analysis techniques, computational tools, the limitations imposed by currently available atomic data, and the validity of standard assumptions. I also discuss the future: challenges associated with future missions and goals for atomic data collection.

  4. Aerothermodynamics of Blunt Body Entry Vehicles. Chapter 3

    NASA Technical Reports Server (NTRS)

    Hollis, Brian R.; Borrelli, Salvatore

    2011-01-01

    In this chapter, the aerothermodynamic phenomena of blunt body entry vehicles are discussed. Four topics will be considered that present challenges to current computational modeling techniques for blunt body environments: turbulent flow, non-equilibrium flow, rarefied flow, and radiation transport. Examples of comparisons between computational tools to ground and flight-test data will be presented in order to illustrate the challenges existing in the numerical modeling of each of these phenomena and to provide test cases for evaluation of Computational Fluid Dynamics (CFD) code predictions.

  5. Aerothermodynamics of blunt body entry vehicles

    NASA Astrophysics Data System (ADS)

    Hollis, Brian R.; Borrelli, Salvatore

    2012-01-01

    In this chapter, the aerothermodynamic phenomena of blunt body entry vehicles are discussed. Four topics will be considered that present challenges to current computational modeling techniques for blunt body environments: turbulent flow, non-equilibrium flow, rarefied flow, and radiation transport. Examples of comparisons between computational tools to ground and flight-test data will be presented in order to illustrate the challenges existing in the numerical modeling of each of these phenomena and to provide test cases for evaluation of computational fluid dynamics (CFD) code predictions.

  6. Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions

    NASA Astrophysics Data System (ADS)

    Chaudhari, Rajan; Heim, Andrew J.; Li, Zhijun

    2015-05-01

    Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of "refined restraints first, modeling next", provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins.

  7. Paradigm Shift in Education: Weaving Social-Emotional Learning into Language and Literacy Instruction

    ERIC Educational Resources Information Center

    Dresser, Rocio

    2013-01-01

    This paper first outlines some of the challenges students and teachers are facing in schools around the country. These challenges include social issues such as violence, drugs and bulling. This coupled with the fact that many instructional programs follow the cognitive-only model and the current push for standardized testing has had a negative…

  8. School Psychology: A Public Health Framework: I. From Evidence-Based Practices to Evidence-Based Policies.

    ERIC Educational Resources Information Center

    Hoagwood, Kimberly; Johnson, Jacqueline

    2003-01-01

    Describes current perspectives on evidence-based practices in psychology, medicine, and education; discusses challenges in the implementation and dissemination of research-based findings into schools; describes differences between current models of organizational behavior as studied in children's mental health services and in education; and…

  9. Systems and context modeling approach to requirements analysis

    NASA Astrophysics Data System (ADS)

    Ahuja, Amrit; Muralikrishna, G.; Patwari, Puneet; Subhrojyoti, C.; Swaminathan, N.; Vin, Harrick

    2014-08-01

    Ensuring completeness and correctness of the requirements for a complex system such as the SKA is challenging. Current system engineering practice includes developing a stakeholder needs definition, a concept of operations, and defining system requirements in terms of use cases and requirements statements. We present a method that enhances this current practice into a collection of system models with mutual consistency relationships. These include stakeholder goals, needs definition and system-of-interest models, together with a context model that participates in the consistency relationships among these models. We illustrate this approach by using it to analyze the SKA system requirements.

  10. Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model--a report on the Virtual Intracranial Stenting Challenge 2007.

    PubMed

    Radaelli, A G; Augsburger, L; Cebral, J R; Ohta, M; Rüfenacht, D A; Balossino, R; Benndorf, G; Hose, D R; Marzo, A; Metcalfe, R; Mortier, P; Mut, F; Reymond, P; Socci, L; Verhegghe, B; Frangi, A F

    2008-07-19

    This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

  11. Towards agile large-scale predictive modelling in drug discovery with flow-based programming design principles.

    PubMed

    Lampa, Samuel; Alvarsson, Jonathan; Spjuth, Ola

    2016-01-01

    Predictive modelling in drug discovery is challenging to automate as it often contains multiple analysis steps and might involve cross-validation and parameter tuning that create complex dependencies between tasks. With large-scale data or when using computationally demanding modelling methods, e-infrastructures such as high-performance or cloud computing are required, adding to the existing challenges of fault-tolerant automation. Workflow management systems can aid in many of these challenges, but the currently available systems are lacking in the functionality needed to enable agile and flexible predictive modelling. We here present an approach inspired by elements of the flow-based programming paradigm, implemented as an extension of the Luigi system which we name SciLuigi. We also discuss the experiences from using the approach when modelling a large set of biochemical interactions using a shared computer cluster.Graphical abstract.

  12. Challenges of NDE Simulation Tool Challenges of NDE Simulation Tool

    NASA Technical Reports Server (NTRS)

    Leckey, Cara A. C.; Juarez, Peter D.; Seebo, Jeffrey P.; Frank, Ashley L.

    2015-01-01

    Realistic nondestructive evaluation (NDE) simulation tools enable inspection optimization and predictions of inspectability for new aerospace materials and designs. NDE simulation tools may someday aid in the design and certification of advanced aerospace components; potentially shortening the time from material development to implementation by industry and government. Furthermore, modeling and simulation are expected to play a significant future role in validating the capabilities and limitations of guided wave based structural health monitoring (SHM) systems. The current state-of-the-art in ultrasonic NDE/SHM simulation cannot rapidly simulate damage detection techniques for large scale, complex geometry composite components/vehicles with realistic damage types. This paper discusses some of the challenges of model development and validation for composites, such as the level of realism and scale of simulation needed for NASA' applications. Ongoing model development work is described along with examples of model validation studies. The paper will also discuss examples of the use of simulation tools at NASA to develop new damage characterization methods, and associated challenges of validating those methods.

  13. Numerical simulation of turbulent combustion: Scientific challenges

    NASA Astrophysics Data System (ADS)

    Ren, ZhuYin; Lu, Zhen; Hou, LingYun; Lu, LiuYan

    2014-08-01

    Predictive simulation of engine combustion is key to understanding the underlying complicated physicochemical processes, improving engine performance, and reducing pollutant emissions. Critical issues as turbulence modeling, turbulence-chemistry interaction, and accommodation of detailed chemical kinetics in complex flows remain challenging and essential for high-fidelity combustion simulation. This paper reviews the current status of the state-of-the-art large eddy simulation (LES)/prob-ability density function (PDF)/detailed chemistry approach that can address the three challenging modelling issues. PDF as a subgrid model for LES is formulated and the hybrid mesh-particle method for LES/PDF simulations is described. Then the development need in micro-mixing models for the PDF simulations of turbulent premixed combustion is identified. Finally the different acceleration methods for detailed chemistry are reviewed and a combined strategy is proposed for further development.

  14. Fast Magnetotail Reconnection: Challenge to Global MHD Modeling

    NASA Astrophysics Data System (ADS)

    Kuznetsova, M. M.; Hesse, M.; Rastaetter, L.; Toth, G.; de Zeeuw, D.; Gombosi, T.

    2005-05-01

    Representation of fast magnetotail reconnection rates during substorm onset is one of the major challenges to global MHD modeling. Our previous comparative study of collisionless magnetic reconnection in GEM Challenge geometry demonstrated that the reconnection rate is controlled by ion nongyrotropic behavior near the reconnection site and that it can be described in terms of nongyrotropic corrections to the magnetic induction equation. To further test the approach we performed MHD simulations with nongyrotropic corrections of forced reconnection for the Newton Challenge setup. As a next step we employ the global MHD code BATSRUS and test different methods to model fast magnetotail reconnection rates by introducing non-ideal corrections to the induction equation in terms of nongyrotropic corrections, spatially localized resistivity, or current dependent resistivity. The BATSRUS adaptive grid structure allows to perform global simulations with spatial resolution near the reconnection site comparable with spatial resolution of local MHD simulations for the Newton Challenge. We select solar wind conditions which drive the accumulation of magnetic field in the tail lobes and subsequent magnetic reconnection and energy release. Testing the ability of global MHD models to describe magnetotail evolution during substroms is one of the elements of science based validation efforts at the Community Coordinated Modeling Center.

  15. Mass-Gathering Medical Care in Electronic Dance Music Festivals.

    PubMed

    FitzGibbon, Kathleen M; Nable, Jose V; Ayd, Benjamin; Lawner, Benjamin J; Comer, Angela C; Lichenstein, Richard; Levy, Matthew J; Seaman, Kevin G; Bussey, Ian

    2017-10-01

    Introduction Electronic dance music (EDM) festivals represent a unique subset of mass-gathering events with limited guidance through literature or legislation to guide mass-gathering medical care at these events. Hypothesis/Problem Electronic dance music festivals pose unique challenges with increased patient encounters and heightened patient acuity under-estimated by current validated casualty predication models. This was a retrospective review of three separate EDM festivals with analysis of patient encounters and patient transport rates. Data obtained were inserted into the predictive Arbon and Hartman models to determine estimated patient presentation rate and patient transport rates. The Arbon model under-predicted the number of patient encounters and the number of patient transports for all three festivals, while the Hartman model under-predicted the number of patient encounters at one festival and over-predicted the number of encounters at the other two festivals. The Hartman model over-predicted patient transport rates for two of the three festivals. Electronic dance music festivals often involve distinct challenges and current predictive models are inaccurate for planning these events. The formation of a cohesive incident action plan will assist in addressing these challenges and lead to the collection of more uniform data metrics. FitzGibbon KM , Nable JV , Ayd B , Lawner BJ , Comer AC , Lichenstein R , Levy MJ , Seaman KG , Bussey I . Mass-gathering medical care in electronic dance music festivals. Prehosp Disaster Med. 2017;32(5):563-567.

  16. Understanding Psychopathology

    PubMed Central

    Krueger, Robert F.; Markon, Kristian E.

    2008-01-01

    Research on psychopathology is at a historical crossroads. New technologies offer the promise of lasting advances in our understanding of the causes of human psychological suffering. Making the best use of these technologies, however, requires an empirically accurate model of psychopathology. Much current research is framed by the model of psychopathology portrayed in current versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM; American Psychiatric Association, 2000). Although the modern DSMs have been fundamental in advancing psychopathology research, recent research also challenges some assumptions made in the DSM—for example, the assumption that all forms of psychopathology are well conceived of as discrete categories. Psychological science has a critical role to play in working through the implications of this research and the challenges it presents. In particular, behavior-genetic, personality, and quantitative-psychological research perspectives can be melded to inform the development of an empirically based model of psychopathology that would constitute an evolution of the DSM. PMID:18392116

  17. The spread of European models of engineering education: the challenges faced in emerging countries

    NASA Astrophysics Data System (ADS)

    Gardelle, Linda; Cardona Gil, Emmanuel; Benguerna, Mohamed; Bolat, Altangul; Naran, Boldmaa

    2017-03-01

    The major European models of engineering training (the German, the British and the French model) spread throughout the world during the twentieth century. Historical heritage, cultural proximity and languages explain the open expression of faithfulness to one system in some countries. In these countries, the national standards inherited are now completed by international standards or are in direct competition with new influences. This article will attempt, through the existing literature, interviews and on-site investigations, to analyse current engineering training in some emerging countries and its relations with European models, the objective being to analyse the evolution of local systems and so the challenges and issues raised by the dissemination of European models.

  18. Equitable Education for All: Using a Comprehensive Instructional Model to Improve Preschool Teacher Practices

    ERIC Educational Resources Information Center

    Carlson, Abby G.; Curby, Timothy W.; Brown, Chavaughn A.; Trygstad, Kelly M.; Truong, Felicia R.

    2017-01-01

    The current study evaluates the effectiveness of a comprehensive instructional model, ("Every Child Ready"), as a vehicle to provide equitable education experiences for all children by compensating for gaps in teacher knowledge. The ECR instructional model addresses several challenges facing the early childhood landscape. Specifically,…

  19. Racial Disparities, Perceptions, and Evaluations: Counseling Model Choice and the Florida College System

    ERIC Educational Resources Information Center

    Ocean, Mia; Hawkins, Damian; Chopra, Kobitta

    2014-01-01

    Community college students face a number of life and academic challenges. It is unknown what counseling models are currently employed by community colleges to meet their students' many needs. Representatives of Florida's 28 community colleges completed a survey detailing their counseling model, student populations, rationale behind the model…

  20. Lake Michigan nearshore: How modeling scenarios can improve dialog between modelers and ecologists

    EPA Science Inventory

    The nearshore of Lake Michigan, similarly to the other Great Lakes, experiences environmental concerns due to excessive eutrophication. Assessing the nearshore is challenging because fluctuating nutrient loads, and ever-changing currents cause this area to exhibit large spatial a...

  1. Challenges in soil erosion research and prediction model development

    USDA-ARS?s Scientific Manuscript database

    Quantification of soil erosion has been traditionally considered as a surface hydrologic process with equations for soil detachment and sediment transport derived from the mechanics and hydraulics of the rainfall and surface flow. Under the current erosion modeling framework, the soil has a constant...

  2. Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission.

    PubMed

    Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet

    2015-01-01

    Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

  3. Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions.

    PubMed

    Sakoda, Lori C; Henderson, Louise M; Caverly, Tanner J; Wernli, Karen J; Katki, Hormuzd A

    2017-12-01

    Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer screening and highlights both challenges and strategies for improving their predictive performance and use in clinical practice. Since the 2011 publication of the National Lung Screening Trial results, numerous prediction models have been proposed to estimate the probability of developing or dying from lung cancer or the probability that a pulmonary nodule is malignant. Respective models appear to exhibit high discriminatory accuracy in identifying individuals at highest risk of lung cancer or differentiating malignant from benign pulmonary nodules. However, validation and critical comparison of the performance of these models in independent populations are limited. Little is also known about the extent to which risk prediction models are being applied in clinical practice and influencing decision-making processes and outcomes related to lung cancer screening. Current evidence is insufficient to determine which lung cancer risk prediction models are most clinically useful and how to best implement their use to optimize screening effectiveness and quality. To address these knowledge gaps, future research should be directed toward validating and enhancing existing risk prediction models for lung cancer and evaluating the application of model-based risk calculators and its corresponding impact on screening processes and outcomes.

  4. The Mock LISA Data Challenge Round 3: New and Improved Sources

    NASA Technical Reports Server (NTRS)

    Baker, John

    2008-01-01

    The Mock LISA Data Challenges are a program to demonstrate and encourage the development of data-analysis capabilities for LISA. Each round of challenges consists of several data sets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants are asked to analyze the data sets and report the maximum information they can infer about the source parameters. The challenges are being released in rounds of increasing complexity and realism. Challenge 3. currently in progress, brings new source classes, now including cosmic-string cusps and primordial stochastic backgrounds, and more realistic signal models for supermassive black-hole inspirals and galactic double white dwarf binaries.

  5. Hyperactivity in Boys with Attention-Deficit/Hyperactivity Disorder (ADHD): A Ubiquitous Core Symptom or Manifestation of Working Memory Deficits?

    ERIC Educational Resources Information Center

    Rapport, Mark D.; Bolden, Jennifer; Kofler, Michael J.; Sarver, Dustin E.; Raiker, Joseph S.; Alderson, R. Matt

    2009-01-01

    Hyperactivity is currently considered a core and ubiquitous feature of attention-deficit/hyperactivity disorder (ADHD); however, an alternative model challenges this premise and hypothesizes a functional relationship between working memory (WM) and activity level. The current study investigated whether children's activity level is functionally…

  6. Issues and Problems in the Current Development of Vocational Education in China

    ERIC Educational Resources Information Center

    Shi, Weiping

    2013-01-01

    Chinese vocational education is currently in its most optimal development period in history. This article discusses several challenges of different dimensions faced by vocational education in China as it develops, such as scale versus quality, development goals, a lifelong vocational education system, and creating model institutions; and puts…

  7. Mechanistic analysis of challenge-response experiments.

    PubMed

    Shotwell, M S; Drake, K J; Sidorov, V Y; Wikswo, J P

    2013-09-01

    We present an application of mechanistic modeling and nonlinear longitudinal regression in the context of biomedical response-to-challenge experiments, a field where these methods are underutilized. In this type of experiment, a system is studied by imposing an experimental challenge, and then observing its response. The combination of mechanistic modeling and nonlinear longitudinal regression has brought new insight, and revealed an unexpected opportunity for optimal design. Specifically, the mechanistic aspect of our approach enables the optimal design of experimental challenge characteristics (e.g., intensity, duration). This article lays some groundwork for this approach. We consider a series of experiments wherein an isolated rabbit heart is challenged with intermittent anoxia. The heart responds to the challenge onset, and recovers when the challenge ends. The mean response is modeled by a system of differential equations that describe a candidate mechanism for cardiac response to anoxia challenge. The cardiac system behaves more variably when challenged than when at rest. Hence, observations arising from this experiment exhibit complex heteroscedasticity and sharp changes in central tendency. We present evidence that an asymptotic statistical inference strategy may fail to adequately account for statistical uncertainty. Two alternative methods are critiqued qualitatively (i.e., for utility in the current context), and quantitatively using an innovative Monte-Carlo method. We conclude with a discussion of the exciting opportunities in optimal design of response-to-challenge experiments. © 2013, The International Biometric Society.

  8. Current progress in patient-specific modeling

    PubMed Central

    2010-01-01

    We present a survey of recent advancements in the emerging field of patient-specific modeling (PSM). Researchers in this field are currently simulating a wide variety of tissue and organ dynamics to address challenges in various clinical domains. The majority of this research employs three-dimensional, image-based modeling techniques. Recent PSM publications mostly represent feasibility or preliminary validation studies on modeling technologies, and these systems will require further clinical validation and usability testing before they can become a standard of care. We anticipate that with further testing and research, PSM-derived technologies will eventually become valuable, versatile clinical tools. PMID:19955236

  9. Modeling nanomaterial environmental fate in aquatic systems.

    PubMed

    Dale, Amy L; Casman, Elizabeth A; Lowry, Gregory V; Lead, Jamie R; Viparelli, Enrica; Baalousha, Mohammed

    2015-03-03

    Mathematical models improve our fundamental understanding of the environmental behavior, fate, and transport of engineered nanomaterials (NMs, chemical substances or materials roughly 1-100 nm in size) and facilitate risk assessment and management activities. Although today's large-scale environmental fate models for NMs are a considerable improvement over early efforts, a gap still remains between the experimental research performed to date on the environmental fate of NMs and its incorporation into models. This article provides an introduction to the current state of the science in modeling the fate and behavior of NMs in aquatic environments. We address the strengths and weaknesses of existing fate models, identify the challenges facing researchers in developing and validating these models, and offer a perspective on how these challenges can be addressed through the combined efforts of modelers and experimentalists.

  10. Modeling pedogenesis at multimillennium timescales: achievements and challenges

    NASA Astrophysics Data System (ADS)

    Finke, Peter

    2013-04-01

    The modeling of soil genesis is a particular case of modeling vadose zone processes, because of the variety in processes to be considered and its large (multimillennium) temporal extent. The particular relevancy of pedogenetic modeling for non-pedologists is that it involves the soil compartment carbon cycle. As most of these processes are driven by water flow, modeling hydrological processes is an inevitable component of (non-empirical) modeling of soil genesis. One particular challenge is that both slow and fast pedogenetic processes need to be accounted for. This overview summarizes the state of the art in this new branch of pedology, achievements made so far and current challenges, and is largely based on one particular pedon-scale soil evolution model, SoilGen. SoilGen is essentially a pedon-scale solute transport model that simulates unsaturated water flow, chemical equilibriums of various species with calcite, gypsum and gibbsite as precipitated phases, an exchange phase of Na, K, Ca, Mg, H and Al on clay and organic matter and a solution phase comprising various cations and anions. Additionally, a number of pedogenetic processes are simulated: C-cycling, chemical weathering of primary minerals, physical weathering of soil particles, bioturbation and clay migration. The model was applied onto a climosequence, a chronosequence, a toposequence and as part of a spatio-temporal soilscape reconstruction. Furthermore, the clay migration component has been calibrated and tested and so has the organic matter decomposition component. Quantitative comparisons between simulations and measurements resulted in the identification of possible improvements in the model and associated inputs, identified problems to be solved and identified the current application domain. Major challenges for process-based modeling in the vadose zone at multimillennium timescales can be divided into 4 groups: (i) Reconstruction of initial and boundary conditions; (ii) Accounting for evolution in soil properties such as soil texture and soil structure; (iii) Developing adequate calibration techniques; (iv) Maximizing computational efficiency. Reconstruction of initial and boundary conditions requires multidisciplinary inputs either derived from proxies or from combined vegetation and climate development models. So far, the combination of pedogenetic models and combined vegetation/climate models is rare. At pedogenetic timescales, soil characteristics that are usually considered constant become dynamic: texture, OC, bulk density, precipitated salts, minerals, etc. Interactions and feedbacks between these characteristics and associated hydrological properties need attention, e.g. via pedotransfer functions. The same can be stated for the development of soil structure and associated preferential flow, which is still a challenge. At multimillennium temporal extents, the combination of long model runtime and the fact that most calibration data represent the current stage of soil development requires a special approach. Model performance can be evaluated at various timescales using unconventional proxies. Finally, recognizing the fact that matter redistribution at the landscape scale is of paramount importance at multimillennium extent requires the formulation of computationally efficient 3D models. This will surely involve analysis of the tradeoff between process detail, model accuracy, required boundary inputs and model runtime.

  11. Virtual reality in surgical training.

    PubMed

    Lange, T; Indelicato, D J; Rosen, J M

    2000-01-01

    Virtual reality in surgery and, more specifically, in surgical training, faces a number of challenges in the future. These challenges are building realistic models of the human body, creating interface tools to view, hear, touch, feel, and manipulate these human body models, and integrating virtual reality systems into medical education and treatment. A final system would encompass simulators specifically for surgery, performance machines, telemedicine, and telesurgery. Each of these areas will need significant improvement for virtual reality to impact medicine successfully in the next century. This article gives an overview of, and the challenges faced by, current systems in the fast-changing field of virtual reality technology, and provides a set of specific milestones for a truly realistic virtual human body.

  12. Current Trends in the Detection of Sociocultural Signatures: Data-Driven Models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sanfilippo, Antonio P.; Bell, Eric B.; Corley, Courtney D.

    The harvesting of behavioral data and their analysis through evidence-based reasoning enable the detection of sociocultural signatures in their context to support situation awareness and decision making. Harvested data are used as training materials from which to infer computational models of sociocultural behaviors or calibrate parameters for such models. Harvested data also serve as evidence input that the models use to provide insights about observed and future behaviors for targets of interest. The harvested data is often the result of assembling diverse data types and aggregating them into a form suitable for analysis. Data need to be analyzed to bringmore » out the categories of content that are relevant to the domain being addressed in order to train or run a model. If, for example, we are modeling the intent of a group to engage in violent behavior using messages that the group has broadcasted, then these messages need to be processed to extract and measure indicators of violent intent. The extracted indicators and the associated measurements (e.g. rates or counts of occurrence) can then be used to train/calibrate and run computational models that assess the propensity for violence expressed in the source message. Ubiquitous access to the Internet, mobile telephony and technologies such as digital photography and digital video have enabled social media application platforms such as Facebook, YouTube, and Twitter that are altering the nature of human social interaction. The fast increasing pace of online social interaction introduces new challenges and opportunities for gathering sociocultural data. Challenges include the development of harvesting and processing techniques tailored to new data environments and formats (e.g. Twitter, Facebook), the integration of social media content with traditional media content, and the protection of personal privacy. As these and other challenges are addressed, a new wealth of behavioral data and data analysis methods becomes available that are shaping social computing as a strongly data-driven experimental discipline with an increasingly stronger impact on the decision-making process of groups and individuals alike. In this chapter, we review current advances and trends in the detection of sociocultural signatures. Specific embodiments of the issues discussed are provided with respect to the assessment of violent intent and sociopolitical contention. We begin by reviewing current approaches to the detection of sociocultural signatures in these domains. Next, we turn to the review of novel data harvesting methods for social media content. Finally, we discuss the application of sociocultural models to social media content, and conclude by commenting on current challenges and future developments.« less

  13. On Verifying Currents and Other Features in the Hawaiian Islands Region Using Fully Coupled Ocean/Atmosphere Mesoscale Prediction System Compared to Global Ocean Model and Ocean Observations

    NASA Astrophysics Data System (ADS)

    Jessen, P. G.; Chen, S.

    2014-12-01

    This poster introduces and evaluates features concerning the Hawaii, USA region using the U.S. Navy's fully Coupled Ocean/Atmosphere Mesoscale Prediction System (COAMPS-OS™) coupled to the Navy Coastal Ocean Model (NCOM). It also outlines some challenges in verifying ocean currents in the open ocean. The system is evaluated using in situ ocean data and initial forcing fields from the operational global Hybrid Coordinate Ocean Model (HYCOM). Verification shows difficulties in modelling downstream currents off the Hawaiian islands (Hawaii's wake). Comparing HYCOM to NCOM current fields show some displacement of small features such as eddies. Generally, there is fair agreement from HYCOM to NCOM in salinity and temperature fields. There is good agreement in SSH fields.

  14. First-Principles-Driven Model-Based Optimal Control of the Current Profile in NSTX-U

    NASA Astrophysics Data System (ADS)

    Ilhan, Zeki; Barton, Justin; Wehner, William; Schuster, Eugenio; Gates, David; Gerhardt, Stefan; Kolemen, Egemen; Menard, Jonathan

    2014-10-01

    Regulation in time of the toroidal current profile is one of the main challenges toward the realization of the next-step operational goals for NSTX-U. A nonlinear, control-oriented, physics-based model describing the temporal evolution of the current profile is obtained by combining the magnetic diffusion equation with empirical correlations obtained at NSTX-U for the electron density, electron temperature, and non-inductive current drives. In this work, the proposed model is embedded into the control design process to synthesize a time-variant, linear-quadratic-integral, optimal controller capable of regulating the safety factor profile around a desired target profile while rejecting disturbances. Neutral beam injectors and the total plasma current are used as actuators to shape the current profile. The effectiveness of the proposed controller in regulating the safety factor profile in NSTX-U is demonstrated via closed-loop predictive simulations carried out in PTRANSP. Supported by PPPL.

  15. Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security

    DOE PAGES

    Christensen, A. J.; Srinivasan, V.; Hart, J. C.; ...

    2018-03-17

    Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have ledmore » to discoveries in “big data” analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. Lastly, this survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.« less

  16. Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Christensen, A. J.; Srinivasan, V.; Hart, J. C.

    Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have ledmore » to discoveries in “big data” analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. Lastly, this survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.« less

  17. Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security.

    PubMed

    Christensen, A J; Srinivasan, Venkatraman; Hart, John C; Marshall-Colon, Amy

    2018-05-01

    Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have led to discoveries in "big data" analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. This survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.

  18. Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security

    PubMed Central

    Christensen, A J; Srinivasan, Venkatraman; Hart, John C; Marshall-Colon, Amy

    2018-01-01

    Abstract Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have led to discoveries in “big data” analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. This survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields. PMID:29562368

  19. Terrestrial Planet Finder Coronagraph Observatory summary

    NASA Technical Reports Server (NTRS)

    Ford, Virginia; Levine-Westa, Marie; Kissila, Andy; Kwacka, Eug; Hoa, Tim; Dumonta, Phil; Lismana, Doug; Fehera, Peter; Cafferty, Terry

    2005-01-01

    Creating an optical space telescope observatory capable of detecting and characterizing light from extra-solar terrestrial planets poses technical challenges related to extreme wavefront stability. The Terrestrial Planet Finder Coronagraph design team has been developing an observatory based on trade studies, modeling and analysis that has guided us towards design choices to enable this challenging mission. This paper will describe the current flight baseline design of the observatory and the trade studies that have been performed. The modeling and analysis of this design will be described including predicted performance and the tasks yet to be done.

  20. Physics-based Control-oriented Modeling of the Current Profile Evolution in NSTX-Upgrade

    NASA Astrophysics Data System (ADS)

    Ilhan, Zeki; Barton, Justin; Shi, Wenyu; Schuster, Eugenio; Gates, David; Gerhardt, Stefan; Kolemen, Egemen; Menard, Jonathan

    2013-10-01

    The operational goals for the NSTX-Upgrade device include non-inductive sustainment of high- β plasmas, realization of the high performance equilibrium scenarios with neutral beam heating, and achievement of longer pulse durations. Active feedback control of the current profile is proposed to enable these goals. Motivated by the coupled, nonlinear, multivariable, distributed-parameter plasma dynamics, the first step towards feedback control design is the development of a physics-based, control-oriented model for the current profile evolution in response to non-inductive current drives and heating systems. For this purpose, the nonlinear magnetic-diffusion equation is coupled with empirical models for the electron density, electron temperature, and non-inductive current drives (neutral beams). The resulting first-principles-driven, control-oriented model is tailored for NSTX-U based on the PTRANSP predictions. Main objectives and possible challenges associated with the use of the developed model for control design are discussed. This work was supported by PPPL.

  1. Estimating the spatial scales of landscape effects on abundance

    Treesearch

    Richard Chandler; Jeffrey Hepinstall-Cymerman

    2016-01-01

    Spatial variation in abundance is influenced by local- and landscape-level environmental variables, but modeling landscape effects is challenging because the spatial scales of the relationships are unknown. Current approaches involve buffering survey locations with polygons of various sizes and using model selection to identify the best scale. The buffering...

  2. Hierarchical Bayesian Models of Subtask Learning

    ERIC Educational Resources Information Center

    Anglim, Jeromy; Wynton, Sarah K. A.

    2015-01-01

    The current study used Bayesian hierarchical methods to challenge and extend previous work on subtask learning consistency. A general model of individual-level subtask learning was proposed focusing on power and exponential functions with constraints to test for inconsistency. To study subtask learning, we developed a novel computer-based booking…

  3. A Skew-Normal Mixture Regression Model

    ERIC Educational Resources Information Center

    Liu, Min; Lin, Tsung-I

    2014-01-01

    A challenge associated with traditional mixture regression models (MRMs), which rest on the assumption of normally distributed errors, is determining the number of unobserved groups. Specifically, even slight deviations from normality can lead to the detection of spurious classes. The current work aims to (a) examine how sensitive the commonly…

  4. Community Dissemination of the Early Start Denver Model: Implications for Science and Practice

    ERIC Educational Resources Information Center

    Vismara, Laurie A.; Young, Gregory S.; Rogers, Sally J.

    2013-01-01

    The growing number of Autism Spectrum Disorder cases exceeds the services available for these children. This increase challenges both researchers and service providers to develop systematic, effective dissemination strategies for transporting university research models to community early intervention (EI) programs. The current study developed an…

  5. Warfighter Neuroendocrinology: Modeling Stress Response, PTSD, and TBI

    DTIC Science & Technology

    studies are challenged by incongruent diagnostic criteria and confounding treatment protocols. Understanding PTSD is not a simple task as there is no...reliable biological predictor or marker for PTSD and diagnoses are heavily reliant on self-reporting. Current treatments include psychotherapy and...pharmacotherapy: it is not very clear how the two intervention methods inform each other and they are not always very successful. In part, these challenges

  6. Empirical estimates to reduce modeling uncertainties of soil organic carbon in permafrost regions: a review of recent progress and remaining challenges

    USGS Publications Warehouse

    Mishra, U.; Jastrow, J.D.; Matamala, R.; Hugelius, G.; Koven, C.D.; Harden, Jennifer W.; Ping, S.L.; Michaelson, G.J.; Fan, Z.; Miller, R.M.; McGuire, A.D.; Tarnocai, C.; Kuhry, P.; Riley, W.J.; Schaefer, K.; Schuur, E.A.G.; Jorgenson, M.T.; Hinzman, L.D.

    2013-01-01

    The vast amount of organic carbon (OC) stored in soils of the northern circumpolar permafrost region is a potentially vulnerable component of the global carbon cycle. However, estimates of the quantity, decomposability, and combustibility of OC contained in permafrost-region soils remain highly uncertain, thereby limiting our ability to predict the release of greenhouse gases due to permafrost thawing. Substantial differences exist between empirical and modeling estimates of the quantity and distribution of permafrost-region soil OC, which contribute to large uncertainties in predictions of carbon–climate feedbacks under future warming. Here, we identify research challenges that constrain current assessments of the distribution and potential decomposability of soil OC stocks in the northern permafrost region and suggest priorities for future empirical and modeling studies to address these challenges.

  7. Fundamental CRISPR-Cas9 tools and current applications in microbial systems.

    PubMed

    Tian, Pingfang; Wang, Jia; Shen, Xiaolin; Rey, Justin Forrest; Yuan, Qipeng; Yan, Yajun

    2017-09-01

    Derived from the bacterial adaptive immune system, CRISPR technology has revolutionized conventional genetic engineering methods and unprecedentedly facilitated strain engineering. In this review, we outline the fundamental CRISPR tools that have been employed for strain optimization. These tools include CRISPR editing, CRISPR interference, CRISPR activation and protein imaging. To further characterize the CRISPR technology, we present current applications of these tools in microbial systems, including model- and non-model industrial microorganisms. Specially, we point out the major challenges of the CRISPR tools when utilized for multiplex genome editing and sophisticated expression regulation. To address these challenges, we came up with strategies that place emphasis on the amelioration of DNA repair efficiency through CRISPR-Cas9-assisted recombineering. Lastly, multiple promising research directions were proposed, mainly focusing on CRISPR-based construction of microbial ecosystems toward high production of desired chemicals.

  8. Computational fluid dynamics-habitat suitability index (CFD-HSI) modelling as an exploratory tool for assessing passability of riverine migratory challenge zones for fish

    USGS Publications Warehouse

    Haro, Alexander J.; Chelminski, Michael; Dudley, Robert W.

    2015-01-01

    We developed two-dimensional computational fluid hydraulics-habitat suitability index (CFD-HSI) models to identify and qualitatively assess potential zones of shallow water depth and high water velocity that may present passage challenges for five major anadromous fish species in a 2.63-km reach of the main stem Penobscot River, Maine, as a result of a dam removal downstream of the reach. Suitability parameters were based on distribution of fish lengths and body depths and transformed to cruising, maximum sustained and sprint swimming speeds. Zones of potential depth and velocity challenges were calculated based on the hydraulic models; ability of fish to pass a challenge zone was based on the percent of river channel that the contiguous zone spanned and its maximum along-current length. Three river flows (low: 99.1 m3 sec-1; normal: 344.9 m3 sec-1; and high: 792.9 m3 sec-1) were modelled to simulate existing hydraulic conditions and hydraulic conditions simulating removal of a dam at the downstream boundary of the reach. Potential depth challenge zones were nonexistent for all low-flow simulations of existing conditions for deeper-bodied fishes. Increasing flows for existing conditions and removal of the dam under all flow conditions increased the number and size of potential velocity challenge zones, with the effects of zones being more pronounced for smaller species. The two-dimensional CFD-HSI model has utility in demonstrating gross effects of flow and hydraulic alteration, but may not be as precise a predictive tool as a three-dimensional model. Passability of the potential challenge zones cannot be precisely quantified for two-dimensional or three-dimensional models due to untested assumptions and incomplete data on fish swimming performance and behaviours.

  9. Beyond Currents: The Next Phase in GOCE Oceanographic Research

    NASA Astrophysics Data System (ADS)

    Bingham, Rory J.; Haines, Keith; Hughes, Chris W.

    2015-03-01

    GOCE has mapped the surface currents of the world’s oceans in unprecedented detail. What is now required is a concerted effort by the oceanographic community to go beyond currents and exploit these measurements for societal benefit. The aim of this review paper is to explore the ways in which this may be achieved, particularly in relation to ocean modelling. With the final gravity models now released, we begin by reviewing the progress GOCE has in made in measuring the ocean’s mean dynamic topography and associated ocean currents. In the light of this progress, we then examine the important oceanographic questions and technical challenges of societal relevance that can potentially be addressed with the help of the observations GOCE has delivered and outline the benefits their solution could deliver. Benefits may either be direct, through, for example, improved ocean modelling and operational forecasting, or indirect through improved understanding of particular oceanographic processes, such as heat transport by the Atlantic meridional overturning circulation or sea level change. Next we consider the technical challenges that must be overcome in bringing GOCE to bear on these problems. In particular we examine how best to use GOCE error information, this being an especially uncertain, underdeveloped and challenging area of investigation, due largely to the fact that such information has not been previously available to the user community. Finally, we consider measures of success; that is, metrics that can be used to quantify any GOCE-enabled progress that the community makes towards answering these questions. Such metrics are essential for demonstrating progress. Ultimately, with this review paper, we aim to paint a road map that will act as an impetus to the oceanography community to exploit the yet untapped potential of GOCE for scientific understanding and societal benefit.

  10. Nuclear Explosion Monitoring Advances and Challenges

    NASA Astrophysics Data System (ADS)

    Baker, G. E.

    2015-12-01

    We address the state-of-the-art in areas important to monitoring, current challenges, specific efforts that illustrate approaches addressing shortcomings in capabilities, and additional approaches that might be helpful. The exponential increase in the number of events that must be screened as magnitude thresholds decrease presents one of the greatest challenges. Ongoing efforts to exploit repeat seismic events using waveform correlation, subspace methods, and empirical matched field processing holds as much "game-changing" promise as anything being done, and further efforts to develop and apply such methods efficiently are critical. Greater accuracy of travel time, signal loss, and full waveform predictions are still needed to better locate and discriminate seismic events. Important developments include methods to model velocities using multiple types of data; to model attenuation with better separation of source, path, and site effects; and to model focusing and defocusing of surface waves. Current efforts to model higher frequency full waveforms are likely to improve source characterization while more effective estimation of attenuation from ambient noise holds promise for filling in gaps. Censoring in attenuation modeling is a critical problem to address. Quantifying uncertainty of discriminants is key to their operational use. Efforts to do so for moment tensor (MT) inversion are particularly important, and fundamental progress on the statistics of MT distributions is the most important advance needed in the near term in this area. Source physics is seeing great progress through theoretical, experimental, and simulation studies. The biggest need is to accurately predict the effects of source conditions on seismic generation. Uniqueness is the challenge here. Progress will depend on studies that probe what distinguishes mechanisms, rather than whether one of many possible mechanisms is consistent with some set of observations.

  11. Mathematical modelling of clostridial acetone-butanol-ethanol fermentation.

    PubMed

    Millat, Thomas; Winzer, Klaus

    2017-03-01

    Clostridial acetone-butanol-ethanol (ABE) fermentation features a remarkable shift in the cellular metabolic activity from acid formation, acidogenesis, to the production of industrial-relevant solvents, solventogensis. In recent decades, mathematical models have been employed to elucidate the complex interlinked regulation and conditions that determine these two distinct metabolic states and govern the transition between them. In this review, we discuss these models with a focus on the mechanisms controlling intra- and extracellular changes between acidogenesis and solventogenesis. In particular, we critically evaluate underlying model assumptions and predictions in the light of current experimental knowledge. Towards this end, we briefly introduce key ideas and assumptions applied in the discussed modelling approaches, but waive a comprehensive mathematical presentation. We distinguish between structural and dynamical models, which will be discussed in their chronological order to illustrate how new biological information facilitates the 'evolution' of mathematical models. Mathematical models and their analysis have significantly contributed to our knowledge of ABE fermentation and the underlying regulatory network which spans all levels of biological organization. However, the ties between the different levels of cellular regulation are not well understood. Furthermore, contradictory experimental and theoretical results challenge our current notion of ABE metabolic network structure. Thus, clostridial ABE fermentation still poses theoretical as well as experimental challenges which are best approached in close collaboration between modellers and experimentalists.

  12. Using a GIS-based spot growth model and visual simulator to evaluate the effects of silvicultural treatments on southern pine beetle-infested stands

    Treesearch

    Chiao-Ying Chou; Roy L. Hedden; Bo Song; Thomas M. Williams

    2013-01-01

    Many models are available for simulating the probability of southern pine beetle (Dendroctonus frontalis Zimmermann) (SPB) infestation and outbreak dynamics. However, only a few models focused on the potential spatial SPB growth. Although the integrated pest management systems are currently adopted, SPB management is still challenging because of...

  13. Chasing the long tail of environmental data: PEcAn is nuts about Brown Dog

    NASA Astrophysics Data System (ADS)

    Dietze, M.; Cowdery, E.; Desai, A. R.; Gardella, A.; Kelly, R.; Kooper, R.; LeBauer, D.; Mantooth, J.; McHenry, K.; Serbin, S.; Shiklomanov, A. N.; Simkins, J.; Viskari, T.; Raiho, A.

    2015-12-01

    The Predictive Ecosystem Analyzer (PEcAn) is a ecological modeling informatics system that manages the flows of information in and out of terrestrial biosphere models, provenance tracking, visualization, analysis, and model-data fusion. We are in the process of scaling the PEcAn system from one that currently supports a handful of models and system nodes to one that aims to provide bottom-up connectivity across much of the model-data integration done by the terrestrial biogeochemistry community. This talk reports on the current state of PEcAn, it's data processing workflows, and the near- and long-term challenges faced. Particular emphasis will be given to the tools being developed by the Brown Dog project to make unstructured, un-curated data more accessible: the Data Access Proxy (DAP) and the Data Tilling Service (DTS). The use of the DAP to process meteorological data and the DTS to read vegetation data will be demonstrated and other Brown Dog environmental case studies will be briefly touched on. Beyond data processing, facilitating data discovery and import into PEcAn and distributing analyses across the PEcAn network (i.e. bringing models to data) are key challenges moving forward.

  14. [Trends in hospital care].

    PubMed

    Vecina Neto, Gonzalo; Malik, Ana Maria

    2007-01-01

    This paper analyses trends in the delivery of hospital services in Brazil, considering the setting, the current situation and its challenges, examining what still remains to be done. The variables studied for the analysis of the setting are: demography, epidemiological profile, human resources, technology, medicalization, costs, review of the role of the citizen, legislation, equity, hospital-centricity and regionalization, care fractioning and bed availability. The Brazilian setting was studied through the supplementary healthcare model, financing and the healthcare area production chain. The observations of the current situation present external evaluation models, outsourcing, public-private relationships, de-hospitalization and financing. The analysis of the challenges examines the need for long range planning, the quest for new legal models for the 'business', the use of information and information systems, cost controls and the need for enhanced efficiency and compliance with legal directives, guaranteed universal access to full healthcare facilities, the inclusion of primary prevention in healthcare procedures, integrating the public and private sectors and engaging physicians in solving problems.

  15. Integrating physical and genetic maps: from genomes to interaction networks

    PubMed Central

    Beyer, Andreas; Bandyopadhyay, Sourav; Ideker, Trey

    2009-01-01

    Physical and genetic mapping data have become as important to network biology as they once were to the Human Genome Project. Integrating physical and genetic networks currently faces several challenges: increasing the coverage of each type of network; establishing methods to assemble individual interaction measurements into contiguous pathway models; and annotating these pathways with detailed functional information. A particular challenge involves reconciling the wide variety of interaction types that are currently available. For this purpose, recent studies have sought to classify genetic and physical interactions along several complementary dimensions, such as ordered versus unordered, alleviating versus aggravating, and first versus second degree. PMID:17703239

  16. Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine

    PubMed Central

    Rongvaux, Anthony; Takizawa, Hitoshi; Strowig, Till; Willinger, Tim; Eynon, Elizabeth E.

    2014-01-01

    To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies. PMID:23330956

  17. Key challenges and priorities for modelling European grasslands under climate change.

    PubMed

    Kipling, Richard P; Virkajärvi, Perttu; Breitsameter, Laura; Curnel, Yannick; De Swaef, Tom; Gustavsson, Anne-Maj; Hennart, Sylvain; Höglind, Mats; Järvenranta, Kirsi; Minet, Julien; Nendel, Claas; Persson, Tomas; Picon-Cochard, Catherine; Rolinski, Susanne; Sandars, Daniel L; Scollan, Nigel D; Sebek, Leon; Seddaiu, Giovanna; Topp, Cairistiona F E; Twardy, Stanislaw; Van Middelkoop, Jantine; Wu, Lianhai; Bellocchi, Gianni

    2016-10-01

    Grassland-based ruminant production systems are integral to sustainable food production in Europe, converting plant materials indigestible to humans into nutritious food, while providing a range of environmental and cultural benefits. Climate change poses significant challenges for such systems, their productivity and the wider benefits they supply. In this context, grassland models have an important role in predicting and understanding the impacts of climate change on grassland systems, and assessing the efficacy of potential adaptation and mitigation strategies. In order to identify the key challenges for European grassland modelling under climate change, modellers and researchers from across Europe were consulted via workshop and questionnaire. Participants identified fifteen challenges and considered the current state of modelling and priorities for future research in relation to each. A review of literature was undertaken to corroborate and enrich the information provided during the horizon scanning activities. Challenges were in four categories relating to: 1) the direct and indirect effects of climate change on the sward 2) climate change effects on grassland systems outputs 3) mediation of climate change impacts by site, system and management and 4) cross-cutting methodological issues. While research priorities differed between challenges, an underlying theme was the need for accessible, shared inventories of models, approaches and data, as a resource for stakeholders and to stimulate new research. Developing grassland models to effectively support efforts to tackle climate change impacts, while increasing productivity and enhancing ecosystem services, will require engagement with stakeholders and policy-makers, as well as modellers and experimental researchers across many disciplines. The challenges and priorities identified are intended to be a resource 1) for grassland modellers and experimental researchers, to stimulate the development of new research directions and collaborative opportunities, and 2) for policy-makers involved in shaping the research agenda for European grassland modelling under climate change. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Workplace Learning and Higher Education in Finland: Reflections on Current Practice

    ERIC Educational Resources Information Center

    Virolainen, Maarit

    2007-01-01

    Purpose: The purpose of this article is to describe the organization of workplace learning in Finnish polytechnics, the models that have been developed for this purpose, and the challenges presented. Design/methodology/approach: First, the models for embedding workplace learning in the curriculum are described and analysed. Second, the conflicting…

  19. A Complex Dynamic Systems Perspective on Identity and Its Development: The Dynamic Systems Model of Role Identity

    ERIC Educational Resources Information Center

    Kaplan, Avi; Garner, Joanna K.

    2017-01-01

    Current prominent models of identity face challenges in bridging across divergent perspectives and apparent dichotomies such as personal or social-collective, conscious or unconscious, and epigenetic or discursive-relational, and affording pursuit of research questions that allows integrative answers. This article presents a coherent theoretical…

  20. Going with the Flow: Challenging Students to Make Assumptions

    ERIC Educational Resources Information Center

    Felton, Mathew D.; Anhalt, Cynthia O.; Cortez, Ricardo

    2015-01-01

    Many current and future teachers have little experience with modeling and how to integrate it into their teaching. However, with the introduction of the Common Core State Standards for Mathematics (CCSSM) and its emphasis on mathematical modeling in all grades (CCSSI 2010), this integration has become paramount. Therefore, middle-grades teachers…

  1. Challenges in Modelling and Control of Offshore De-oiling Hydrocyclone Systems

    NASA Astrophysics Data System (ADS)

    Durdevic, Petar; Pedersen, Simon; Yang, Zhenyu

    2017-01-01

    Offshore de-oiling installations are facing an increasing challenge with regards to removing oil residuals from produced water prior to discharge into the ocean. The de-oiling of produced water is initially achieved in the primary separation processes using gravity-based multi-phase separators, which can effectively handle large amounts of oil-well fluids but may struggle with the efficient separation of small dispersed oil particles. Thereby hydrocyclone systems are commonly employed in the downstream Produced Water Treatment (PWT) process for further reducing the oil concentration in the produced water before it can be discharged into the ocean. The popularity of hydrocyclone technology in the offshore oil and gas industry is mainly due to its rugged design and low maintenance requirements. However, to operate and control this type of system in an efficient way is far less simple, and alternatively this task imposes a number of key control challenges. Specifically, there is much research to be performed in the direction of dynamic modelling and control of de-oiling hydrocyclone systems. The current solutions rely heavily on empirical trial-and-error approaches. This paper gives a brief review of current hydrocyclone control solutions and the remaining challenges and includes some of our recent work in this topic and ends with a motivation for future work.

  2. Dynamics of the Earth's Inner Magnetosphere and its Connection to the Ionosphere: Current Understanding and Challenges

    NASA Technical Reports Server (NTRS)

    Zheng, Yihua

    2010-01-01

    The Earth's inner magnetosphere, a vast volume in space spanning from 1.5 Re (Earth radii) to 10 Re, is a host to a variety of plasma populations (with energy from 1 eV to few MeV) and physical processes where most of which involve plasma and field coupling. As a gigantic particle accelerator, the inner magnetosphere includes three overlapping regions: the plasmasphere, the ring current, and the Van Allen radiation belt. The complex structures and dynamics of these regions are externally driven by solar activities and internally modulated by intricate interactions and coupling. As a major constituent of Space Weather, the inner magnetosphere is both scientifically intriguing and practically important to our society. In this presentation, I will discuss our recent results from the Comprehensive Ring Current Model, in the context of our current understanding of the inner magnetosphere in general and challenges ahead in making further progresses.

  3. Dynamics of the Earth's Inner Magnetosphere and Its Connection to the Ionosphere: Current Understanding and Challenges

    NASA Technical Reports Server (NTRS)

    Zheng, Yihua

    2011-01-01

    The Earth's inner magnetosphere, a vast volume in space spanning from 1.5 Re (Earth radii) to 10 Re, is a host to a variety of plasma populations (with energy from 1 eV to few MeV) and physical processes where most of which involve plasma and field coupling. As a gigantic particle accelerator, the inner magnetosphere includes three overlapping regions: the plasmasphere, the ring current, and the Van Allen radiation belt. The complex structures and dynamics of these regions are externally driven by solar activities and internally modulated by intricate interactions and coupling. As a major constituent of Space Weather, the inner magnetosphere is both scientifically intriguing and practically important to our society. In this presentation, I will discuss our recent results from the Comprehensive Ring Current Model, in the context of our current understanding of the inner magnetosphere in general and challenges ahead in making further progresses.

  4. Issues and Challenges in Situation Assessment (Level 2 Fusion)

    DTIC Science & Technology

    2006-12-01

    2 SAW–Comprehension of the current situa- tion ² Level 3 SAW–Projection of future states Operators of dynamic systems use their SAW in de - termining...1) build a model by either editing an existing template/model or create a new one; (2) activate/ de -activate existing models; or (3) view active models...and any evidence that has been associated with the model over time. Different political, military, economic, social , infrastructure, and informa

  5. A Comparison of Combustor-Noise Models

    NASA Technical Reports Server (NTRS)

    Hultgren, Lennart, S.

    2012-01-01

    The current status of combustor-noise prediction in the NASA Aircraft Noise Prediction Program (ANOPP) for current-generation (N) turbofan engines is summarized. Best methods for near-term updates are reviewed. Long-term needs and challenges for the N+1 through N+3 timeframe are discussed. This work was carried out under the NASA Fundamental Aeronautics Program, Subsonic Fixed Wing Project, Quiet Aircraft Subproject.

  6. Preclinical magnetic resonance imaging and systems biology in cancer research: current applications and challenges.

    PubMed

    Albanese, Chris; Rodriguez, Olga C; VanMeter, John; Fricke, Stanley T; Rood, Brian R; Lee, YiChien; Wang, Sean S; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F; Wang, Yue

    2013-02-01

    Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. On the role of model-based monitoring for adaptive planning under uncertainty

    NASA Astrophysics Data System (ADS)

    Raso, Luciano; Kwakkel, Jan; Timmermans, Jos; Haasnoot, Mariolijn

    2016-04-01

    Adaptive plans, designed to anticipate and respond to an unfolding uncertain future, have found a fertile application domain in the planning of deltas that are exposed to rapid socioeconomic development and climate change. Adaptive planning, under the moniker of adaptive delta management, is used in the Dutch Delta Program for developing a nation-wide plan to prepare for uncertain climate change and socio-economic developments. Scientifically, adaptive delta management relies heavily on Dynamic Adaptive Policy Pathways. Currently, in the Netherlands the focus is shifting towards implementing the adaptive delta plan. This shift is especially relevant because the efficacy of adaptive plans hinges on monitoring on-going developments and ensuring that actions are indeed taken if and when necessary. In the design of an effective monitoring system for an adaptive plan, three challenges have to be confronted: • Shadow of the past: The development of adaptive plans and the design of their monitoring system relies heavily on current knowledge of the system, and current beliefs about plausible future developments. A static monitoring system is therefore exposed to the exact same uncertainties one tries to address through adaptive planning. • Inhibition of learning: Recent applications of adaptive planning tend to overlook the importance of learning and new information, and fail to account for this explicitly in the design of adaptive plans. • Challenge of surprise: Adaptive policies are designed in light of the current foreseen uncertainties. However, developments that are not considered during the design phase as being plausible could still substantially affect the performance of adaptive policies. The shadow of the past, the inhibition of learning, and the challenge of surprise taken together suggest that there is a need for redesigning the concepts of monitoring and evaluation to support the implementation of adaptive plans. Innovations from control theory, triggered by the challenge of uncertainty in operational control, may offer solutions from which monitoring for adaptive planning can benefit. Specifically: (i) in control, observations are incorporated into the model through data assimilation, updating the present state, boundary conditions, and parameters based on new observations, diminishing the shadow of the past; (ii) adaptive control is a way to modify the characteristics of the internal model, incorporating new knowledge on the system, countervailing the inhibition of learning; and (iii) in closed-loop control, a continuous system update equips the controller with "inherent robustness", i.e. to capacity to adapts to new conditions even when these were not initially considered. We aim to explore how inherent robustness addresses the challenge of surprise. Innovations in model-based control might help to improve and adapt the models used to support adaptive delta management to new information (reducing uncertainty). Moreover, this would offer a starting point for using these models not only in the design of adaptive plans, but also as part of the monitoring. The proposed research requires multidisciplinary cooperation between control theory, the policy sciences, and integrated assessment modeling.

  8. Current Challenges in Health Economic Modeling of Cancer Therapies: A Research Inquiry

    PubMed Central

    Miller, Jeffrey D.; Foley, Kathleen A.; Russell, Mason W.

    2014-01-01

    Background The demand for economic models that evaluate cancer treatments is increasing, as healthcare decision makers struggle for ways to manage their budgets while providing the best care possible to patients with cancer. Yet, after nearly 2 decades of cultivating and refining techniques for modeling the cost-effectiveness and budget impact of cancer therapies, serious methodologic and policy challenges have emerged that question the adequacy of economic modeling as a sound decision-making tool in oncology. Objectives We sought to explore some of the contentious issues associated with the development and use of oncology economic models as informative tools in current healthcare decision-making. Our objective was to draw attention to these complex pharmacoeconomic concerns and to promote discussion within the oncology and health economics research communities. Methods Using our combined expertise in health economics research and economic modeling, we structured our inquiry around the following 4 questions: (1) Are economic models adequately addressing questions relevant to oncology decision makers; (2) What are the methodologic limitations of oncology economic models; (3) What guidelines are followed for developing oncology economic models; and (4) Is the evolution of oncology economic modeling keeping pace with treatment innovation? Within the context of each of these questions, we discuss issues related to the technical limitations of oncology modeling, the availability of adequate data for developing models, and the problems with how modeling analyses and results are presented and interpreted. Discussion There is general acceptance that economic models are good, essential tools for decision-making, but the practice of oncology and its rapidly evolving technologies present unique challenges that make assessing and demonstrating value especially complex. There is wide latitude for improvement in oncology modeling methodologies and how model results are presented and interpreted. Conclusion Complex technical and data availability issues with oncology economic modeling pose serious concerns that need to be addressed. It is our hope that this article will provide a framework to guide future discourse on this important topic. PMID:24991399

  9. Current challenges in health economic modeling of cancer therapies: a research inquiry.

    PubMed

    Miller, Jeffrey D; Foley, Kathleen A; Russell, Mason W

    2014-05-01

    The demand for economic models that evaluate cancer treatments is increasing, as healthcare decision makers struggle for ways to manage their budgets while providing the best care possible to patients with cancer. Yet, after nearly 2 decades of cultivating and refining techniques for modeling the cost-effectiveness and budget impact of cancer therapies, serious methodologic and policy challenges have emerged that question the adequacy of economic modeling as a sound decision-making tool in oncology. We sought to explore some of the contentious issues associated with the development and use of oncology economic models as informative tools in current healthcare decision-making. Our objective was to draw attention to these complex pharmacoeconomic concerns and to promote discussion within the oncology and health economics research communities. Using our combined expertise in health economics research and economic modeling, we structured our inquiry around the following 4 questions: (1) Are economic models adequately addressing questions relevant to oncology decision makers; (2) What are the methodologic limitations of oncology economic models; (3) What guidelines are followed for developing oncology economic models; and (4) Is the evolution of oncology economic modeling keeping pace with treatment innovation? Within the context of each of these questions, we discuss issues related to the technical limitations of oncology modeling, the availability of adequate data for developing models, and the problems with how modeling analyses and results are presented and interpreted. There is general acceptance that economic models are good, essential tools for decision-making, but the practice of oncology and its rapidly evolving technologies present unique challenges that make assessing and demonstrating value especially complex. There is wide latitude for improvement in oncology modeling methodologies and how model results are presented and interpreted. Complex technical and data availability issues with oncology economic modeling pose serious concerns that need to be addressed. It is our hope that this article will provide a framework to guide future discourse on this important topic.

  10. Update - Concept of Operations for Integrated Model-Centric Engineering at JPL

    NASA Technical Reports Server (NTRS)

    Bayer, Todd J.; Bennett, Matthew; Delp, Christopher L.; Dvorak, Daniel; Jenkins, Steven J.; Mandutianu, Sanda

    2011-01-01

    The increasingly ambitious requirements levied on JPL's space science missions, and the development pace of such missions, challenge our current engineering practices. All the engineering disciplines face this growth in complexity to some degree, but the challenges are greatest in systems engineering where numerous competing interests must be reconciled and where complex system level interactions must be identified and managed. Undesired system-level interactions are increasingly a major risk factor that cannot be reliably exposed by testing, and natural-language single-viewpoint specifications areinadequate to capture and expose system level interactions and characteristics. Systems engineering practices must improve to meet these challenges, and the most promising approach today is the movement toward a more integrated and model-centric approach to mission conception, design, implementation and operations. This approach elevates engineering models to a principal role in systems engineering, gradually replacing traditional document centric engineering practices.

  11. Molecular modeling: An open invitation for applied mathematics

    NASA Astrophysics Data System (ADS)

    Mezey, Paul G.

    2013-10-01

    Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

  12. Supercomputer requirements for selected disciplines important to aerospace

    NASA Technical Reports Server (NTRS)

    Peterson, Victor L.; Kim, John; Holst, Terry L.; Deiwert, George S.; Cooper, David M.; Watson, Andrew B.; Bailey, F. Ron

    1989-01-01

    Speed and memory requirements placed on supercomputers by five different disciplines important to aerospace are discussed and compared with the capabilities of various existing computers and those projected to be available before the end of this century. The disciplines chosen for consideration are turbulence physics, aerodynamics, aerothermodynamics, chemistry, and human vision modeling. Example results for problems illustrative of those currently being solved in each of the disciplines are presented and discussed. Limitations imposed on physical modeling and geometrical complexity by the need to obtain solutions in practical amounts of time are identified. Computational challenges for the future, for which either some or all of the current limitations are removed, are described. Meeting some of the challenges will require computer speeds in excess of exaflop/s (10 to the 18th flop/s) and memories in excess of petawords (10 to the 15th words).

  13. Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

    PubMed

    Konstorum, Anna; Vella, Anthony T; Adler, Adam J; Laubenbacher, Reinhard C

    2017-06-01

    The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development. © 2017 The Author(s).

  14. Modeling the spatial distribution of forest crown biomass and effects on fire behavior with FUEL3D and WFDS

    Treesearch

    Russell A. Parsons; William Mell; Peter McCauley

    2010-01-01

    Crown fire poses challenges to fire managers and can endanger fire fighters. Understanding of how fire interacts with tree crowns is essential to informed decisions about crown fire. Current operational crown fire predictions in the United States assume homogeneous crown fuels. While a new class of research fire models, which model fire behavior with computational...

  15. Big Data Provenance: Challenges, State of the Art and Opportunities.

    PubMed

    Wang, Jianwu; Crawl, Daniel; Purawat, Shweta; Nguyen, Mai; Altintas, Ilkay

    2015-01-01

    Ability to track provenance is a key feature of scientific workflows to support data lineage and reproducibility. The challenges that are introduced by the volume, variety and velocity of Big Data, also pose related challenges for provenance and quality of Big Data, defined as veracity. The increasing size and variety of distributed Big Data provenance information bring new technical challenges and opportunities throughout the provenance lifecycle including recording, querying, sharing and utilization. This paper discusses the challenges and opportunities of Big Data provenance related to the veracity of the datasets themselves and the provenance of the analytical processes that analyze these datasets. It also explains our current efforts towards tracking and utilizing Big Data provenance using workflows as a programming model to analyze Big Data.

  16. Alzheimer’s in 3D culture: Challenges and perspectives

    PubMed Central

    D'Avanzo, Carla; Aronson, Jenna; Kim, Young Hye; Choi, Se Hoon; Tanzi, Rudolph E.; Kim, Doo Yeon

    2015-01-01

    Summary Alzheimer’s disease (AD) is the most common cause of dementia, and there is currently no cure. The “β-amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. PMID:26252541

  17. Mock Data Challenge for the MPD/NICA Experiment on the HybriLIT Cluster

    NASA Astrophysics Data System (ADS)

    Gertsenberger, Konstantin; Rogachevsky, Oleg

    2018-02-01

    Simulation of data processing before receiving first experimental data is an important issue in high-energy physics experiments. This article presents the current Event Data Model and the Mock Data Challenge for the MPD experiment at the NICA accelerator complex which uses ongoing simulation studies to exercise in a stress-testing the distributed computing infrastructure and experiment software in the full production environment from simulated data through the physical analysis.

  18. Applying Knowledge Discovery in Databases in Public Health Data Set: Challenges and Concerns

    PubMed Central

    Volrathongchia, Kanittha

    2003-01-01

    In attempting to apply Knowledge Discovery in Databases (KDD) to generate a predictive model from a health care dataset that is currently available to the public, the first step is to pre-process the data to overcome the challenges of missing data, redundant observations, and records containing inaccurate data. This study will demonstrate how to use simple pre-processing methods to improve the quality of input data. PMID:14728545

  19. Software Systems for High-performance Quantum Computing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Humble, Travis S; Britt, Keith A

    Quantum computing promises new opportunities for solving hard computational problems, but harnessing this novelty requires breakthrough concepts in the design, operation, and application of computing systems. We define some of the challenges facing the development of quantum computing systems as well as software-based approaches that can be used to overcome these challenges. Following a brief overview of the state of the art, we present models for the quantum programming and execution models, the development of architectures for hybrid high-performance computing systems, and the realization of software stacks for quantum networking. This leads to a discussion of the role that conventionalmore » computing plays in the quantum paradigm and how some of the current challenges for exascale computing overlap with those facing quantum computing.« less

  20. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    PubMed

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  1. Minimal Unified Resolution to R_{K^{(*)}} and R(D^{(*)}) Anomalies with Lepton Mixing.

    PubMed

    Choudhury, Debajyoti; Kundu, Anirban; Mandal, Rusa; Sinha, Rahul

    2017-10-13

    It is a challenging task to explain, in terms of a simple and compelling new physics scenario, the intriguing discrepancies between the standard model expectations and the data for the neutral-current observables R_{K} and R_{K^{*}}, as well as the charged-current observables R(D) and R(D^{*}). We show that this can be achieved in an effective theory with only two unknown parameters. In addition, this class of models predicts some interesting signatures in the context of both B decays as well as high-energy collisions.

  2. Bringing computational models of bone regeneration to the clinic.

    PubMed

    Carlier, Aurélie; Geris, Liesbet; Lammens, Johan; Van Oosterwyck, Hans

    2015-01-01

    Although the field of bone regeneration has experienced great advancements in the last decades, integrating all the relevant, patient-specific information into a personalized diagnosis and optimal treatment remains a challenging task due to the large number of variables that affect bone regeneration. Computational models have the potential to cope with this complexity and to improve the fundamental understanding of the bone regeneration processes as well as to predict and optimize the patient-specific treatment strategies. However, the current use of computational models in daily orthopedic practice is very limited or inexistent. We have identified three key hurdles that limit the translation of computational models of bone regeneration from bench to bed side. First, there exists a clear mismatch between the scope of the existing and the clinically required models. Second, most computational models are confronted with limited quantitative information of insufficient quality thereby hampering the determination of patient-specific parameter values. Third, current computational models are only corroborated with animal models, whereas a thorough (retrospective and prospective) assessment of the computational model will be crucial to convince the health care providers of the capabilities thereof. These challenges must be addressed so that computational models of bone regeneration can reach their true potential, resulting in the advancement of individualized care and reduction of the associated health care costs. © 2015 Wiley Periodicals, Inc.

  3. A new EMI system for detection and classification of challenging targets

    NASA Astrophysics Data System (ADS)

    Shubitidze, F.; Fernández, J. P.; Barrowes, B. E.; O'Neill, K.

    2013-06-01

    Advanced electromagnetic induction (EMI) sensors currently feature multi-axis illumination of targets and tri-axial vector sensing (e.g., MetalMapper), or exploit multi-static array data acquisition (e.g., TEMTADS). They produce data of high density, quality, and diversity, and have been combined with advanced EMI models to provide superb classification performance relative to the previous generation of single-axis, monostatic sensors. However, these advances yet have to improve significantly our ability to classify small, deep, and otherwise challenging targets. Particularly, recent live-site discrimination studies at Camp Butner, NC and Camp Beale, CA have revealed that it is more challenging to detect and discriminate small munitions (with calibers ranging from 20 mm to 60 mm) than larger ones. In addition, a live-site test at the Massachusetts Military Reservation, MA highlighted the difficulties for current sensors to classify large, deep, and overlapping targets with high confidence. There are two main approaches to overcome these problems: 1) adapt advanced EMI models to the existing systems and 2) improve the detection limits of current sensors by modifying their hardware. In this paper we demonstrate a combined software/hardware approach that will provide extended detection range and spatial resolution to next-generation EMI systems; we analyze and invert EMI data to extract classification features for small and deep targets; and we propose a new system that features a large transmitter coil.

  4. Conceptual Resources for Constructing the Concepts of Electricity: The Role of Models, Analogies and Imagination

    ERIC Educational Resources Information Center

    Taber, Keith S.; de Trafford, Tom; Quail, Teresa

    2006-01-01

    The topic of electricity offers considerable challenge for the teacher hoping to provide students with an insight into scientific ways of thinking about circuits. The concepts used to make sense of electric circuits are abstract and students are expected to develop conceptual models of the relationship between non-observable qualities (current,…

  5. Immigration, Racial Profiling, and White Privilege: Community-Based Challenges and Practices for Adult Educators

    ERIC Educational Resources Information Center

    Kong, Luis J.

    2010-01-01

    In this chapter, the author will explore the significance of race from a social constructionist perspective. He will focus on immigration laws and on examples of legal cases that have set the stage for current definitions of whiteness and racial identification. A community-based transformational organizing model will be presented. The model will…

  6. Determinants of Multiple Semantic Priming: A Meta-Analysis and Spike Frequency Adaptive Model of a Cortical Network

    ERIC Educational Resources Information Center

    Lavigne, Frederic; Dumercy, Laurent; Darmon, Nelly

    2011-01-01

    Recall and language comprehension while processing sequences of words involves multiple semantic priming between several related and/or unrelated words. Accounting for multiple and interacting priming effects in terms of underlying neuronal structure and dynamics is a challenge for current models of semantic priming. Further elaboration of current…

  7. Hybrid modeling for quality by design and PAT-benefits and challenges of applications in biopharmaceutical industry.

    PubMed

    von Stosch, Moritz; Davy, Steven; Francois, Kjell; Galvanauskas, Vytautas; Hamelink, Jan-Martijn; Luebbert, Andreas; Mayer, Martin; Oliveira, Rui; O'Kennedy, Ronan; Rice, Paul; Glassey, Jarka

    2014-06-01

    This report highlights the drivers, challenges, and enablers of the hybrid modeling applications in biopharmaceutical industry. It is a summary of an expert panel discussion of European academics and industrialists with relevant scientific and engineering backgrounds. Hybrid modeling is viewed in its broader sense, namely as the integration of different knowledge sources in form of parametric and nonparametric models into a hybrid semi-parametric model, for instance the integration of fundamental and data-driven models. A brief description of the current state-of-the-art and industrial uptake of the methodology is provided. The report concludes with a number of recommendations to facilitate further developments and a wider industrial application of this modeling approach. These recommendations are limited to further exploiting the benefits of this methodology within process analytical technology (PAT) applications in biopharmaceutical industry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Producing Cochrane systematic reviews-a qualitative study of current approaches and opportunities for innovation and improvement.

    PubMed

    Turner, Tari; Green, Sally; Tovey, David; McDonald, Steve; Soares-Weiser, Karla; Pestridge, Charlotte; Elliott, Julian

    2017-08-01

    Producing high-quality, relevant systematic reviews and keeping them up to date is challenging. Cochrane is a leading provider of systematic reviews in health. For Cochrane to continue to contribute to improvements in heath, Cochrane Reviews must be rigorous, reliable and up to date. We aimed to explore existing models of Cochrane Review production and emerging opportunities to improve the efficiency and sustainability of these processes. To inform discussions about how to best achieve this, we conducted 26 interviews and an online survey with 106 respondents. Respondents highlighted the importance and challenge of creating reliable, timely systematic reviews. They described the challenges and opportunities presented by current production models, and they shared what they are doing to improve review production. They particularly highlighted significant challenges with increasing complexity of review methods; difficulty keeping authors on board and on track; and the length of time required to complete the process. Strong themes emerged about the roles of authors and Review Groups, the central actors in the review production process. The results suggest that improvements to Cochrane's systematic review production models could come from improving clarity of roles and expectations, ensuring continuity and consistency of input, enabling active management of the review process, centralising some review production steps; breaking reviews into smaller "chunks", and improving approaches to building capacity of and sharing information between authors and Review Groups. Respondents noted the important role new technologies have to play in enabling these improvements. The findings of this study will inform the development of new Cochrane Review production models and may provide valuable data for other systematic review producers as they consider how best to produce rigorous, reliable, up-to-date reviews.

  9. Liquid-metal-ion source development for space propulsion at ARC.

    PubMed

    Tajmar, M; Scharlemann, C; Genovese, A; Buldrini, N; Steiger, W; Vasiljevich, I

    2009-04-01

    The Austrian Research Centers have a long history of developing indium Liquid-Metal-Ion Source (LMIS) for space applications including spacecraft charging compensators, SIMS and propulsion. Specifically the application as a thruster requires long-term operation as well as high-current operation which is very challenging. Recently, we demonstrated the operation of a cluster of single LMIS at an average current of 100muA each for more than 4800h and developed models for tip erosion and droplet deposition suggesting that such a LMIS can operate up to 20,000h or more. In order to drastically increase the current, a porous multi-tip source that allows operation up to several mA was developed. Our paper will highlight the problem areas and challenges from our LMIS development focusing on space propulsion applications.

  10. The laboratory workforce shortage: a managerial perspective.

    PubMed

    Cortelyou-Ward, Kendall; Ramirez, Bernardo; Rotarius, Timothy

    2011-01-01

    Most clinical laboratories in the nation report severe difficulties in recruitment and retention of most types of personnel. Other important factors impacting this problem include work complexities, increased automation, and a graying workforce. As a further challenge, institutional needs for clinical laboratory personnel are expected to grow significantly in the next decade. This article examines the current situation of the clinical laboratory workforce. It analyzes the different types of personnel; the managerial, supervision, and line positions that are key for different types of laboratories; the job outlook and recent projections for different types of staff; and the current issues, trends, and challenges of the laboratory workforce. Laboratory managers need to take action with strategies suggested for overcoming these challenges. Most importantly, they need to become transformational leaders by developing effective staffing models, fostering healthy and productive work environments, and creating value with a strategic management culture and implementation of knowledge management.

  11. Challenges to promoting health for amateur athletes through anti-doping policy.

    PubMed

    Henning, April

    2017-01-01

    Anti-doping regulations are intended, at least in part, to promote the health of athletes. While most anti-doping efforts target elite and professional competitors, there have been recent moves by sport governing bodies to expand anti-doping testing to include amateur athletes. Drawing on previous critiques of anti-doping policies and illustrating cases, this article outlines five of the challenges to health promotion of applying the current detect and ban model to the amateur level of sport. I argue that the current approach is not effective and, in some ways, may undermine the goal of health promotion at the amateur level. In order to address these challenges, I propose alternative, health-centred strategies that focus on athlete empowerment and choice through critical awareness of a variety of substances, associated risks and rewards, and the role of expertise in decision-making.

  12. Challenges to promoting health for amateur athletes through anti-doping policy

    PubMed Central

    Henning, April

    2017-01-01

    Anti-doping regulations are intended, at least in part, to promote the health of athletes. While most anti-doping efforts target elite and professional competitors, there have been recent moves by sport governing bodies to expand anti-doping testing to include amateur athletes. Drawing on previous critiques of anti-doping policies and illustrating cases, this article outlines five of the challenges to health promotion of applying the current detect and ban model to the amateur level of sport. I argue that the current approach is not effective and, in some ways, may undermine the goal of health promotion at the amateur level. In order to address these challenges, I propose alternative, health-centred strategies that focus on athlete empowerment and choice through critical awareness of a variety of substances, associated risks and rewards, and the role of expertise in decision-making. PMID:28736489

  13. Chikungunya Virus: Pathophysiology, Mechanism, and Modeling

    PubMed Central

    Ganesan, Vaishnavi K.; Reid, St Patrick

    2017-01-01

    Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models. PMID:29194359

  14. A Bayesian context fear learning algorithm/automaton

    PubMed Central

    Krasne, Franklin B.; Cushman, Jesse D.; Fanselow, Michael S.

    2015-01-01

    Contextual fear conditioning is thought to involve the synaptic plasticity-dependent establishment in hippocampus of representations of to-be-conditioned contexts which can then become associated with USs in the amygdala. A conceptual and computational model of this process is proposed in which contextual attributes are assumed to be sampled serially and randomly during contextual exposures. Given this assumption, moment-to-moment information about such attributes will often be quite different from one exposure to another and, in particular, between exposures during which representations are created, exposures during which conditioning occurs, and during recall sessions. This presents challenges to current conceptual models of hippocampal function. In order to meet these challenges, our model's hippocampus was made to operate in different modes during representation creation and recall, and non-hippocampal machinery was constructed that controlled these hippocampal modes. This machinery uses a comparison between contextual information currently observed and information associated with existing hippocampal representations of familiar contexts to compute the Bayesian Weight of Evidence that the current context is (or is not) a known one, and it uses this value to assess the appropriateness of creation or recall modes. The model predicts a number of known phenomena such as the immediate shock deficit, spurious fear conditioning to contexts that are absent but similar to actually present ones, and modulation of conditioning by pre-familiarization with contexts. It also predicts a number of as yet unknown phenomena. PMID:26074792

  15. Reviewing Biosphere Reserves globally: effective conservation action or bureaucratic label?

    PubMed

    Coetzer, Kaera L; Witkowski, Edward T F; Erasmus, Barend F N

    2014-02-01

    The Biosphere Reserve (BR) model of UNESCO's Man and the Biosphere Programme reflects a shift towards more accountable conservation. Biosphere Reserves attempt to reconcile environmental protection with sustainable development; they explicitly acknowledge humans, and human interests in the conservation landscape while still maintaining the ecological values of existing protected areas. Conceptually, this model is attractive, with 610 sites currently designated globally. Yet the practical reality of implementing dual 'conservation' and 'development' goals is challenging, with few examples successfully conforming to the model's full criteria. Here, we review the history of Biosphere Reserves from first inception in 1974 to the current status quo, and examine the suitability of the designation as an effective conservation model. We track the spatial expansion of Biosphere Reserves globally, assessing the influence of the Statutory Framework of the World Network of Biosphere Reserves and Seville strategy in 1995, when the BR concept refocused its core objectives on sustainable development. We use a comprehensive range of case studies to discuss conformity to the Programme, the social and ecological consequences associated with implementation of the designation, and challenges in aligning conservation and development. Given that the 'Biosphere Reserve' label is a relatively unknown designation in the public arena, this review also provides details on popularising the Biosphere Reserve brand, as well as prospects for further research, currently unexploited, but implicit in the designation. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  16. JAMS - a software platform for modular hydrological modelling

    NASA Astrophysics Data System (ADS)

    Kralisch, Sven; Fischer, Christian

    2015-04-01

    Current challenges of understanding and assessing the impacts of climate and land use changes on environmental systems demand for an ever-increasing integration of data and process knowledge in corresponding simulation models. Software frameworks that allow for a seamless creation of integrated models based on less complex components (domain models, process simulation routines) have therefore gained increasing attention during the last decade. JAMS is an Open-Source software framework that has been especially designed to cope with the challenges of eco-hydrological modelling. This is reflected by (i) its flexible approach for representing time and space, (ii) a strong separation of process simulation components from the declarative description of more complex models using domain specific XML, (iii) powerful analysis and visualization functions for spatial and temporal input and output data, and (iv) parameter optimization and uncertainty analysis functions commonly used in environmental modelling. Based on JAMS, different hydrological and nutrient-transport simulation models were implemented and successfully applied during the last years. We will present the JAMS core concepts and give an overview of models, simulation components and support tools available for that framework. Sample applications will be used to underline the advantages of component-based model designs and to show how JAMS can be used to address the challenges of integrated hydrological modelling.

  17. Extending the surrogacy analogy: applying the advance directive model to biobanks.

    PubMed

    Solomon, Stephanie; Mongoven, Ann

    2015-01-01

    Biobank donors and biobank governance face a conceptual challenge akin to clinical patients and their designated surrogate decision-makers, the necessity of making decisions and policies now that must be implemented under future unknown circumstances. We propose that biobanks take advantage of this parallel to learn lessons from the historical trajectory of advance directives and develop models analogous to current 'best practice' advance directives such as Values Histories and TheFive Wishes. We suggest how such models could improve biobanks' engagement both with communities and with individual donors by being more honest about the limits of current disclosure and eliciting information to ensure the protection of donor interests more robustly through time than current 'informed consent' processes in biobanking. © 2014 S. Karger AG, Basel.

  18. A novel model for through-silicon via (TSV) filling process simulation considering three additives and current density effect

    NASA Astrophysics Data System (ADS)

    Wang, Fuliang; Zhao, Zhipeng; Wang, Feng; Wang, Yan; Nie, Nantian

    2017-12-01

    Through-silicon via (TSV) filling by electrochemical deposition is still a challenge for 3D IC packaging, and three-component additive systems (accelerator, suppressor, and leveler) were commonly used in the industry to achieve void-free filling. However, models considering three additive systems and the current density effect have not been fully studied. In this paper, a novel three-component model was developed to study the TSV filling mechanism and process, where the interaction behavior of the three additives (accelerator, suppressor, and leveler) were considered, and the adsorption, desorption, and consumption coefficient of the three additives were changed with the current density. Based on this new model, the three filling types (seam void, ‘V’ shape, and key hole) were simulated under different current density conditions, and the filling results were verified by experiments. The effect of the current density on the copper ion concentration, additives surface coverage, and local current density distribution during the TSV filling process were obtained. Based on the simulation and experimental results, the diffusion-adsorption-desorption-consumption competition behavior between the suppressor, the accelerator, and the leveler were discussed. The filling mechanisms under different current densities were also analyzed.

  19. The subtle body: an interoceptive map of central nervous system function and meditative mind-brain-body integration.

    PubMed

    Loizzo, Joseph J

    2016-06-01

    Meditation research has begun to clarify the brain effects and mechanisms of contemplative practices while generating a range of typologies and explanatory models to guide further study. This comparative review explores a neglected area relevant to current research: the validity of a traditional central nervous system (CNS) model that coevolved with the practices most studied today and that provides the first comprehensive neural-based typology and mechanistic framework of contemplative practices. The subtle body model, popularly known as the chakra system from Indian yoga, was and is used as a map of CNS function in traditional Indian and Tibetan medicine, neuropsychiatry, and neuropsychology. The study presented here, based on the Nalanda tradition, shows that the subtle body model can be cross-referenced with modern CNS maps and challenges modern brain maps with its embodied network model of CNS function. It also challenges meditation research by: (1) presenting a more rigorous, neural-based typology of contemplative practices; (2) offering a more refined and complete network model of the mechanisms of contemplative practices; and (3) serving as an embodied, interoceptive neurofeedback aid that is more user friendly and complete than current teaching aids for clinical and practical applications of contemplative practice. © 2016 New York Academy of Sciences.

  20. Predicting hydrological and erosional risks in fire-affected watersheds: recent advances and research gaps

    NASA Astrophysics Data System (ADS)

    Nunes, João Pedro; Keizer, Jan Jacob

    2017-04-01

    Models can be invaluable tools to assess and manage the impacts of forest fires on hydrological and erosion processes. Immediately after fires, models can be used to identify priority areas for post-fire interventions or assess the risks of flooding and downstream contamination. In the long term, models can be used to evaluate the long-term implications of a fire regime for soil protection, surface water quality and potential management risks, or determine how changes to fire regimes, caused e.g. by climate change, can impact soil and water quality. However, several challenges make post-fire modelling particularly difficult: • Fires change vegetation cover and properties, such as by changing soil water repellency or by adding an ash layer over the soil; these processes, however are not described in currently used models, so that existing models need to be modified and tested. • Vegetation and soils recover with time since fire, changing important model parameters, so that the recovery processes themselves also need to be simulated, including the role of post-fire interventions. • During the window of vegetation and soil disturbance, particular weather conditions, such as the occurrence of severe droughts or extreme rainfall events, can have a large impact on the amount of runoff and erosion produced in burnt areas, so that models that smooth out these peak responses and rather simulate "long-term" average processes are less useful. • While existing models can simulate reasonable well slope-scale runoff generation and associated sediment losses and their catchment-scale routing, few models can accommodate the role of the ash layer or its transport by overland flow, in spite of its importance for soil fertility losses and downstream contamination. This presentation will provide an overview of the importance of post-fire hydrological and erosion modelling as well as of the challenges it faces and of recent efforts made to overcome these challenges. It will illustrate these challenges with two examples: probabilistic approaches to simulate the impact of different vegetation regrowth and post-fire climate combinations on runoff and erosion; and model developments for post-fire soil water repellency with different levels of complexity. It will also present an inventory of the current state-of-the-art and propose future research directions, both on post-fire models themselves and on their integration with other models in large-scale water resource assessment management.

  1. PBPK models for the prediction of in vivo performance of oral dosage forms.

    PubMed

    Kostewicz, Edmund S; Aarons, Leon; Bergstrand, Martin; Bolger, Michael B; Galetin, Aleksandra; Hatley, Oliver; Jamei, Masoud; Lloyd, Richard; Pepin, Xavier; Rostami-Hodjegan, Amin; Sjögren, Erik; Tannergren, Christer; Turner, David B; Wagner, Christian; Weitschies, Werner; Dressman, Jennifer

    2014-06-16

    Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the formulation and interplay with the underlying physiological properties of the GI tract. The ability to accurately predict oral drug absorption during drug product development is becoming more relevant given the current challenges facing the pharmaceutical industry. Physiologically-based pharmacokinetic (PBPK) modeling provides an approach that enables the plasma concentration-time profiles to be predicted from preclinical in vitro and in vivo data and can thus provide a valuable resource to support decisions at various stages of the drug development process. Whilst there have been quite a few successes with PBPK models identifying key issues in the development of new drugs in vivo, there are still many aspects that need to be addressed in order to maximize the utility of the PBPK models to predict drug absorption, including improving our understanding of conditions in the lower small intestine and colon, taking the influence of disease on GI physiology into account and further exploring the reasons behind population variability. Importantly, there is also a need to create more appropriate in vitro models for testing dosage form performance and to streamline data input from these into the PBPK models. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the current status of PBPK models available. The current challenges in PBPK set-ups for oral drug absorption including the composition of GI luminal contents, transit and hydrodynamics, permeability and intestinal wall metabolism are discussed in detail. Further, the challenges regarding the appropriate integration of results from in vitro models, such as consideration of appropriate integration/estimation of solubility and the complexity of the in vitro release and precipitation data, are also highlighted as important steps to advancing the application of PBPK models in drug development. It is expected that the "innovative" integration of in vitro data from more appropriate in vitro models and the enhancement of the GI physiology component of PBPK models, arising from the OrBiTo project, will lead to a significant enhancement in the ability of PBPK models to successfully predict oral drug absorption and advance their role in preclinical and clinical development, as well as for regulatory applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

    EPA Science Inventory

    For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

  3. COST MODELS FOR WATER SUPPLY DISTRIBUTION SYSTEMS

    EPA Science Inventory

    A major challenge for society in the twenty-first century will be replacement, design and optimal management of urban infrastructure. It is estimated that the current world wide demand for infrastructure investment is approximately three trillion dollars annually. A Drinking Wate...

  4. Modeling and Simulations in Photoelectrochemical Water Oxidation: From Single Level to Multiscale Modeling.

    PubMed

    Zhang, Xueqing; Bieberle-Hütter, Anja

    2016-06-08

    This review summarizes recent developments, challenges, and strategies in the field of modeling and simulations of photoelectrochemical (PEC) water oxidation. We focus on water splitting by metal-oxide semiconductors and discuss topics such as theoretical calculations of light absorption, band gap/band edge, charge transport, and electrochemical reactions at the electrode-electrolyte interface. In particular, we review the mechanisms of the oxygen evolution reaction, strategies to lower overpotential, and computational methods applied to PEC systems with particular focus on multiscale modeling. The current challenges in modeling PEC interfaces and their processes are summarized. At the end, we propose a new multiscale modeling approach to simulate the PEC interface under conditions most similar to those of experiments. This approach will contribute to identifying the limitations at PEC interfaces. Its generic nature allows its application to a number of electrochemical systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. A systematic review of the challenges to implementation of the patient-centred medical home: lessons for Australia.

    PubMed

    Janamian, Tina; Jackson, Claire L; Glasson, Nicola; Nicholson, Caroline

    2014-08-04

    To review the available literature to identify the major challenges and barriers to implementation and adoption of the patient-centred medical home (PCMH) model, topical in current Australian primary care reforms. Systematic review of peer-reviewed literature. PubMed and Embase databases were searched in December 2012 for studies published in English between January 2007 and December 2012. Studies of any type were included if they defined PCMH using the Patient-Centered Primary Care Collaborative Joint Principles, and reported data on challenges and barriers to implementation and adoption of the PCMH model. One researcher with content knowledge in the area abstracted data relating to the review objective and study design from eligible articles. A second researcher reviewed the abstracted data alongside the original article to check for accuracy and completeness. Thematic synthesis was used to in three stages: free line-by-line coding of data; organisation of "free codes" into related areas to construct "descriptive" themes and develop "analytical" themes. The main barriers identified related to: challenges with the transformation process; difficulties associated with change management; challenges in implementing and using an electronic health record that administers principles of PCMH; challenges with funding and appropriate payment models; insufficient resources and infrastructure within practices; and inadequate measures of performance. This systematic review documents the key challenges and barriers to implementing the PCMH model in United States family practice. It provides valuable evidence for Australian clinicians, policymakers, and organisations approaching adoption of PCMH elements within reform initiatives in this country.

  6. SpaceNet: Modeling and Simulating Space Logistics

    NASA Technical Reports Server (NTRS)

    Lee, Gene; Jordan, Elizabeth; Shishko, Robert; de Weck, Olivier; Armar, Nii; Siddiqi, Afreen

    2008-01-01

    This paper summarizes the current state of the art in interplanetary supply chain modeling and discusses SpaceNet as one particular method and tool to address space logistics modeling and simulation challenges. Fundamental upgrades to the interplanetary supply chain framework such as process groups, nested elements, and cargo sharing, enabled SpaceNet to model an integrated set of missions as a campaign. The capabilities and uses of SpaceNet are demonstrated by a step-by-step modeling and simulation of a lunar campaign.

  7. Challenges in Clinical Management of Radiation-Induced Illnesses in Exploration Spaceflight

    NASA Technical Reports Server (NTRS)

    Blue, Rebecca; Chancellor, Jeffery; Suresh, Rahul; Carnell, Lisa; Reyes, David; Nowadly, Craig; Antonsen, Erik

    2018-01-01

    Historical solar particle events (SPEs) provide context for some understanding of acute radiation exposure risk to astronauts traveling outside of low Earth orbit. Modeling of potential doses delivered to exploration crewmembers anticipates limited radiation-induced health impacts, including prodromal symptoms of nausea, emesis, and fatigue, but suggests that more severe clinical manifestations are unlikely. Recent large animal-model research in space-analogs closely mimicking SPEs has identified coagulopathic events independent of the hematopoietic sequelae of higher radiation doses, similar in manifestation to disseminated intravascular coagulation (DIC). We explored the challenges of clinical management of radiation-related clinical manifestations, using currently accepted modeling techniques and anticipated physiological sequelae, to identify medical capabilities needed to successfully manage SPE-induced radiation illnesses during exploration spaceflight.

  8. Quantifying the economic risks of climate change

    NASA Astrophysics Data System (ADS)

    Diaz, Delavane; Moore, Frances

    2017-11-01

    Understanding the value of reducing greenhouse-gas emissions matters for policy decisions and climate risk management, but quantification is challenging because of the complex interactions and uncertainties in the Earth and human systems, as well as normative ethical considerations. Current modelling approaches use damage functions to parameterize a simplified relationship between climate variables, such as temperature change, and economic losses. Here we review and synthesize the limitations of these damage functions and describe how incorporating impacts, adaptation and vulnerability research advances and empirical findings could substantially improve damage modelling and the robustness of social cost of carbon values produced. We discuss the opportunities and challenges associated with integrating these research advances into cost-benefit integrated assessment models, with guidance for future work.

  9. (Extreme) Core-collapse Supernova Simulations

    NASA Astrophysics Data System (ADS)

    Mösta, Philipp

    2017-01-01

    In this talk I will present recent progress on modeling core-collapse supernovae with massively parallel simulations on the largest supercomputers available. I will discuss the unique challenges in both input physics and computational modeling that come with a problem involving all four fundamental forces and relativistic effects and will highlight recent breakthroughs overcoming these challenges in full 3D simulations. I will pay particular attention to how these simulations can be used to reveal the engines driving some of the most extreme explosions and conclude by discussing what remains to be done in simulation work to maximize what we can learn from current and future time-domain astronomy transient surveys.

  10. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  11. Future Supply Chains Enabled by Continuous Processing-Opportunities Challenges May 20-21 2014 Continuous Manufacturing Symposium.

    PubMed

    Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

    2015-03-01

    This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily "continuous processing"-based supply chain. The current predominantly "large batch" and centralized manufacturing system designed for the "blockbuster" drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more "flow-through" operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Big Data Provenance: Challenges, State of the Art and Opportunities

    PubMed Central

    Wang, Jianwu; Crawl, Daniel; Purawat, Shweta; Nguyen, Mai; Altintas, Ilkay

    2017-01-01

    Ability to track provenance is a key feature of scientific workflows to support data lineage and reproducibility. The challenges that are introduced by the volume, variety and velocity of Big Data, also pose related challenges for provenance and quality of Big Data, defined as veracity. The increasing size and variety of distributed Big Data provenance information bring new technical challenges and opportunities throughout the provenance lifecycle including recording, querying, sharing and utilization. This paper discusses the challenges and opportunities of Big Data provenance related to the veracity of the datasets themselves and the provenance of the analytical processes that analyze these datasets. It also explains our current efforts towards tracking and utilizing Big Data provenance using workflows as a programming model to analyze Big Data. PMID:29399671

  13. Psychosocial health challenges of the elderly in Nigeria: a narrative review.

    PubMed

    Animasahun, Victor J; Chapman, Helena J

    2017-06-01

    Globally, national health systems are challenged to build successful aging models to prepare for biomedical, psychological and social changes. The integral component of psychosocial health in overall quality of life and well-being, however, is underscored and requires greater focus. Changing demographics in Nigeria, in addition to cultural considerations and absence of a social security system, present unique challenges to elderly. We aimed to review the literature that describes the current situation and challenges in psychosocial health status in the elderly in Nigeria and provide recommendations that promote health and well-being during the aging process. Four primary factors affect psychosocial health status of elderly Nigerians, namely: changes in family dynamics, increased demand for healthcare services, increased economic stress, and decreased functional independence. Like other developing countries, the Nigerian national system faces similar challenges in preparing a national framework that can maximize coverage to citizens in the midst of demographic changes in aging. By focusing on five target areas such as the educational system, health services, community-based initiatives, local or regional policies and national strategies, current framework in Nigeria can be modified to prepare for changing demographics in aging.

  14. Support time-dependent transformations for surveying and GIS : current status and upcoming challenges

    NASA Astrophysics Data System (ADS)

    Mahmoudabadi, H.; Lercier, D.; Vielliard, S.; Mein, N.; Briggs, G.

    2016-12-01

    The support of time-dependent transformations for surveying and GIS is becoming a critical issue. We need to convert positions from the realizations of the International Terrestrial Reference Frame to any national reference frame. This problem is easy to solve when all of the required information is available. But it becomes really complicated in a worldwide context. We propose an overview of the current ITRF-aligned reference frames and we describe a global solution to support time-dependent transformations between them and the International Terrestrial Reference Frame. We focus on the uncertainties of station velocities used. In a first approximation, we use a global tectonic plate model to calculate point velocities. We show the impact of the velocity model on the coordinate accuracies. Several countries, particularly in active regions, are developing semi-dynamic reference frames. These frames include local displacement models updated regularly and/or after major events (such as earthquakes). Their integration into surveying or GIS applications is an upcoming challenge. We want to encourage the geodetic community to develop and use standard formats.

  15. Future supply chains enabled by continuous processing--opportunities and challenges. May 20-21, 2014 Continuous Manufacturing Symposium.

    PubMed

    Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

    2015-03-01

    This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily "continuous processing"-based supply chain. The current predominantly "large batch" and centralized manufacturing system designed for the "blockbuster" drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more "flow-through" operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The significant opportunities to moving to a supply chain flow-through operating model, with substantial opportunities in inventory reduction, lead-time to patient, and radically different product assurance/stability regimes. Scenarios for decentralized production models producing a greater variety of products with enhanced volume flexibility. Production, supply, and value chain footprints that are radically different from today's monolithic and centralized batch manufacturing operations. Clinical trial and drug product development cost savings that support more rapid scale-up and market entry models with early involvement of SC designers within New Product Development. The major supply chain and industrial transformational challenges that need to be addressed. The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Response to Intervention (RtI) in the Social, Emotional, and Behavioral Domains: Current Challenges and Emerging Possibilities

    ERIC Educational Resources Information Center

    Saeki, Elina; Jimerson, Shane R.; Earhart, James; Hart, Shelley R.; Renshaw, Tyler; Singh, Renee D.; Stewart, Kaitlyn

    2011-01-01

    As many schools move toward a three-tier model that incorporates a Response to Intervention (RtI) service delivery model in the social, emotional, and behavioral domains, school psychologists may provide leadership. The decision-making process for filtering students through multiple tiers of support and intervention and examining change is an area…

  17. Urgent Need for Improved Mental Health Care and a More Collaborative Model of Care

    PubMed Central

    Lake, James; Turner, Mason Spain

    2017-01-01

    Current treatments and the dominant model of mental health care do not adequately address the complex challenges of mental illness, which accounts for roughly one-third of adult disability globally. These circumstances call for radical change in the paradigm and practices of mental health care, including improving standards of clinician training, developing new research methods, and re-envisioning current models of mental health care delivery. Because of its dominant position in the US health care marketplace and its commitment to research and innovation, Kaiser Permanente (KP) is strategically positioned to make important contributions that will shape the future of mental health care nationally and globally. This article reviews challenges facing mental health care and proposes an agenda for developing a collaborative care model in primary care settings that incorporates conventional biomedical therapies and complementary and alternative medicine approaches. By moving beyond treatment delivery via telephone and secure video and providing earlier interventions through primary care clinics, KP is shifting the paradigm of mental health care to a collaborative care model focusing on prevention. Recommendations are to expand current practices to include integrative treatment strategies incorporating evidence-based biomedical and complementary and alternative medicine modalities that can be provided to patients using a collaborative care model. Recommendations also are made for an internal research program aimed at investigating the efficacy and cost-effectiveness of promising complementary and alternative medicine and integrative treatments addressing the complex needs of patients with severe psychiatric disorders, many of whom respond poorly to treatments available in KP mental health clinics. PMID:28898197

  18. Current-limiting challenges for all-spin logic devices

    PubMed Central

    Su, Li; Zhang, Youguang; Klein, Jacques-Olivier; Zhang, Yue; Bournel, Arnaud; Fert, Albert; Zhao, Weisheng

    2015-01-01

    All-spin logic device (ASLD) has attracted increasing interests as one of the most promising post-CMOS device candidates, thanks to its low power, non-volatility and logic-in-memory structure. Here we investigate the key current-limiting factors and develop a physics-based model of ASLD through nano-magnet switching, the spin transport properties and the breakdown characteristic of channel. First, ASLD with perpendicular magnetic anisotropy (PMA) nano-magnet is proposed to reduce the critical current (Ic0). Most important, the spin transport efficiency can be enhanced by analyzing the device structure, dimension, contact resistance as well as material parameters. Furthermore, breakdown current density (JBR) of spin channel is studied for the upper current limitation. As a result, we can deduce current-limiting conditions and estimate energy dissipation. Based on the model, we demonstrate ASLD with different structures and channel materials (graphene and copper). Asymmetric structure is found to be the optimal option for current limitations. Copper channel outperforms graphene in term of energy but seriously suffers from breakdown current limit. By exploring the current limit and performance tradeoffs, the optimization of ASLD is also discussed. This benchmarking model of ASLD opens up new prospects for design and implementation of future spintronics applications. PMID:26449410

  19. Modeling approaches for characterizing and evaluating environmental exposure to engineered nanomaterials in support of risk-based decision making.

    PubMed

    Hendren, Christine Ogilvie; Lowry, Michael; Grieger, Khara D; Money, Eric S; Johnston, John M; Wiesner, Mark R; Beaulieu, Stephen M

    2013-02-05

    As the use of engineered nanomaterials becomes more prevalent, the likelihood of unintended exposure to these materials also increases. Given the current scarcity of experimental data regarding fate, transport, and bioavailability, determining potential environmental exposure to these materials requires an in depth analysis of modeling techniques that can be used in both the near- and long-term. Here, we provide a critical review of traditional and emerging exposure modeling approaches to highlight the challenges that scientists and decision-makers face when developing environmental exposure and risk assessments for nanomaterials. We find that accounting for nanospecific properties, overcoming data gaps, realizing model limitations, and handling uncertainty are key to developing informative and reliable environmental exposure and risk assessments for engineered nanomaterials. We find methods suited to recognizing and addressing significant uncertainty to be most appropriate for near-term environmental exposure modeling, given the current state of information and the current insufficiency of established deterministic models to address environmental exposure to engineered nanomaterials.

  20. Flood Forecasting in Wales: Challenges and Solutions

    NASA Astrophysics Data System (ADS)

    How, Andrew; Williams, Christopher

    2015-04-01

    With steep, fast-responding river catchments, exposed coastal reaches with large tidal ranges and large population densities in some of the most at-risk areas; flood forecasting in Wales presents many varied challenges. Utilising advances in computing power and learning from best practice within the United Kingdom and abroad have seen significant improvements in recent years - however, many challenges still remain. Developments in computing and increased processing power comes with a significant price tag; greater numbers of data sources and ensemble feeds brings a better understanding of uncertainty but the wealth of data needs careful management to ensure a clear message of risk is disseminated; new modelling techniques utilise better and faster computation, but lack the history of record and experience gained from the continued use of more established forecasting models. As a flood forecasting team we work to develop coastal and fluvial forecasting models, set them up for operational use and manage the duty role that runs the models in real time. An overview of our current operational flood forecasting system will be presented, along with a discussion on some of the solutions we have in place to address the challenges we face. These include: • real-time updating of fluvial models • rainfall forecasting verification • ensemble forecast data • longer range forecast data • contingency models • offshore to nearshore wave transformation • calculation of wave overtopping

  1. Establishing Design Storm Values from Climate Models in Coastal Regions: Challenges and Opportunities

    EPA Science Inventory

    Dynamic interactions of atmospheric and hydrological processes result in large spatiotemporal changes of precipitation and wind speed in coastal storm events under both current and future climates. This variability can impact the design and sustainability of water infrastructure ...

  2. Modeling Watershed Mercury Response to Atmospheric Loadings: Response Time and Challenges

    EPA Science Inventory

    The relationship between sources of mercury to watersheds and its fate in surface waters is invariably complex. Large scale monitoring studies, such as the METAALICUS project, have advanced current understanding of the links between atmospheric deposition of mercury and accumulat...

  3. US Food Security and Climate Change: Mid-Century Projections of Commodity Crop Production by the IMPACT Model

    NASA Astrophysics Data System (ADS)

    Takle, E. S.; Gustafson, D. I.; Beachy, R.; Nelson, G. C.; Mason-D'Croz, D.; Palazzo, A.

    2013-12-01

    Agreement is developing among agricultural scientists on the emerging inability of agriculture to meet growing global food demands. The lack of additional arable land and availability of freshwater have long been constraints on agriculture. Changes in trends of weather conditions that challenge physiological limits of crops, as projected by global climate models, are expected to exacerbate the global food challenge toward the middle of the 21st century. These climate- and constraint-driven crop production challenges are interconnected within a complex global economy, where diverse factors add to price volatility and food scarcity. We use the DSSAT crop modeling suite, together with mid-century projections of four AR4 global models, as input to the International Food Policy Research Institute IMPACT model to project the impact of climate change on food security through the year 2050 for internationally traded crops. IMPACT is an iterative model that responds to endogenous and exogenous drivers to dynamically solve for the world prices that ensure global supply equals global demand. The modeling methodology reconciles the limited spatial resolution of macro-level economic models that operate through equilibrium-driven relationships at a national level with detailed models of biophysical processes at high spatial resolution. The analysis presented here suggests that climate change in the first half of the 21st century does not represent a near-term threat to food security in the US due to the availability of adaptation strategies (e.g., loss of current growing regions is balanced by gain of new growing regions). However, as climate continues to trend away from 20th century norms current adaptation measures will not be sufficient to enable agriculture to meet growing food demand. Climate scenarios from higher-level carbon emissions exacerbate the food shortfall, although uncertainty in climate model projections (particularly precipitation) is a limitation to impact studies.

  4. High-resolution Modeling Assisted Design of Customized and Individualized Transcranial Direct Current Stimulation Protocols

    PubMed Central

    Bikson, Marom; Rahman, Asif; Datta, Abhishek; Fregni, Felipe; Merabet, Lotfi

    2012-01-01

    Objectives Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity currents facilitating or inhibiting spontaneous neuronal activity. tDCS is attractive since dose is readily adjustable by simply changing electrode number, position, size, shape, and current. In the recent past, computational models have been developed with increased precision with the goal to help customize tDCS dose. The aim of this review is to discuss the incorporation of high-resolution patient-specific computer modeling to guide and optimize tDCS. Methods In this review, we discuss the following topics: (i) The clinical motivation and rationale for models of transcranial stimulation is considered pivotal in order to leverage the flexibility of neuromodulation; (ii) The protocols and the workflow for developing high-resolution models; (iii) The technical challenges and limitations of interpreting modeling predictions, and (iv) Real cases merging modeling and clinical data illustrating the impact of computational models on the rational design of rehabilitative electrotherapy. Conclusions Though modeling for non-invasive brain stimulation is still in its development phase, it is predicted that with increased validation, dissemination, simplification and democratization of modeling tools, computational forward models of neuromodulation will become useful tools to guide the optimization of clinical electrotherapy. PMID:22780230

  5. Investigating EMIC Wave Dynamics with RAM-SCB-E

    NASA Astrophysics Data System (ADS)

    Jordanova, V. K.; Fu, X.; Henderson, M. G.; Morley, S.; Welling, D. T.; Yu, Y.

    2017-12-01

    The distribution of ring current ions and electrons in the inner magnetosphere depends strongly on their transport in realistic electric (E) and magnetic (B) fields and concurrent energization or loss. To investigate the high variability of energetic particle (H+, He+, O+, and electron) fluxes during storms selected by the GEM Surface Charging Challenge, we use our kinetic ring current model (RAM) two-way coupled with a 3-D magnetic field code (SCB). This model was just extended to include electric field calculations, making it a unique, fully self-consistent, anisotropic ring current-atmosphere interactions model, RAM-SCB-E. Recently we investigated electromagnetic ion cyclotron (EMIC) instability in a local plasma using both linear theory and nonlinear hybrid simulations and derived a scaling formula that relates the saturation EMIC wave amplitude to initial plasma conditions. Global dynamic EMIC wave maps obtained with our RAM-SCB-E model using this scaling will be presented and compared with statistical models. These plasma waves can affect significantly both ion and electron precipitation into the atmosphere and the subsequent patterns of ionospheric conductance, as well as the global ring current dynamics.

  6. Occupational lead poisoning: who should conduct surveillance and training?

    PubMed

    Keogh, J P; Gordon, J

    1994-11-01

    This commentary challenges the current employer-controlled model for delivering occupational health services. Problems emanating from traditional employer-based medical surveillance and worker education programs for occupational lead poisoning are identified. A new public health model for delivering these services is proposed. This model utilizes a case-based and hazard-based method for bringing workplaces and employers into the program and features direct delivery of surveillance and training services by public health agencies.

  7. Anti-Ebola therapies based on monoclonal antibodies: Current state and challenges ahead

    PubMed Central

    González-González, E; Alvarez, MM; Márquez-Ipiña, AR; Santiago, G Trujillo-de; Rodríguez-Martínez, LM; Annabi, N; Khademhosseini, A

    2017-01-01

    The 2014 Ebola outbreak, the largest recorded, took us largely unprepared, with no available vaccine or specific treatment. In this context, the World Health Organization (WHO) declared that the humanitarian use of experimental therapies against Ebola Virus (EBOV) is ethical. In particular, an experimental treatment consisting of a cocktail of three monoclonal antibodies (mAbs) produced in tobacco plants and specifically directed to the Ebola virus glycoprotein (GP) was tested in humans, apparently with good results. Several mAbs with high affinity to the GP have been described. This review discusses our current knowledge on this topic. Particular emphasis is devoted to those mAbs that have been assayed in animal models or humans as possible therapies against Ebola. Engineering aspects and challenges for the production of anti-Ebola mAbs are also briefly discussed; current platforms for the design and production of full-length mAbs are cumbersome and costly. PMID:26611830

  8. Anti-Ebola therapies based on monoclonal antibodies: current state and challenges ahead.

    PubMed

    González-González, Everardo; Alvarez, Mario Moisés; Márquez-Ipiña, Alan Roberto; Trujillo-de Santiago, Grissel; Rodríguez-Martínez, Luis Mario; Annabi, Nasim; Khademhosseini, Ali

    2017-02-01

    The 2014 Ebola outbreak, the largest recorded, took us largely unprepared, with no available vaccine or specific treatment. In this context, the World Health Organization declared that the humanitarian use of experimental therapies against Ebola Virus (EBOV) is ethical. In particular, an experimental treatment consisting of a cocktail of three monoclonal antibodies (mAbs) produced in tobacco plants and specifically directed to the EBOV glycoprotein (GP) was tested in humans, apparently with good results. Several mAbs with high affinity to the GP have been described. This review discusses our current knowledge on this topic. Particular emphasis is devoted to those mAbs that have been assayed in animal models or humans as possible therapies against Ebola. Engineering aspects and challenges for the production of anti-Ebola mAbs are also briefly discussed; current platforms for the design and production of full-length mAbs are cumbersome and costly.

  9. Influence of photo-generated carriers on current spreading in double diode structures for electroluminescent cooling

    NASA Astrophysics Data System (ADS)

    Radevici, Ivan; Tiira, Jonna; Sadi, Toufik; Oksanen, Jani

    2018-05-01

    Current crowding close to electrical contacts is a common challenge in all optoelectronic devices containing thin current spreading layers (CSLs). We analyze the effects of current spreading on the operation of the so-called double diode structure (DDS), consisting of a light emitting diode (LED) and a photodiode (PD) fabricated within the same epitaxial growth process, and providing an attractive platform for studying electroluminescent (EL) cooling under high bias conditions. We show that current spreading in the common n-type layer between the LED and the PD can be dramatically improved by the strong optical coupling between the diodes, as the coupling enables a photo-generated current through the PD. This reduces the current in the DDS CSL and enables the study of EL cooling using structures that are not limited by the conventional light extraction challenges encountered in normal LEDs. The current spreading in the structures is studied using optical imaging techniques, electrical measurements, simulations, as well as simple equivalent circuit models developed for this purpose. The improved current spreading leads further to a mutual dependence with the coupling efficiency, which is expected to facilitate the process of optimizing the DDS. We also report a new improved value of 63% for the DDS coupling quantum efficiency.

  10. Current challenges in quantifying preferential flow through the vadose zone

    NASA Astrophysics Data System (ADS)

    Koestel, John; Larsbo, Mats; Jarvis, Nick

    2017-04-01

    In this presentation, we give an overview of current challenges in quantifying preferential flow through the vadose zone. A review of the literature suggests that current generation models do not fully reflect the present state of process understanding and empirical knowledge of preferential flow. We believe that the development of improved models will be stimulated by the increasingly widespread application of novel imaging technologies as well as future advances in computational power and numerical techniques. One of the main challenges in this respect is to bridge the large gap between the scales at which preferential flow occurs (pore to Darcy scales) and the scale of interest for management (fields, catchments, regions). Studies at the pore scale are being supported by the development of 3-D non-invasive imaging and numerical simulation techniques. These studies are leading to a better understanding of how macropore network topology and initial/boundary conditions control key state variables like matric potential and thus the strength of preferential flow. Extrapolation of this knowledge to larger scales would require support from theoretical frameworks such as key concepts from percolation and network theory, since we lack measurement technologies to quantify macropore networks at these large scales. Linked hydro-geophysical measurement techniques that produce highly spatially and temporally resolved data enable investigation of the larger-scale heterogeneities that can generate preferential flow patterns at pedon, hillslope and field scales. At larger regional and global scales, improved methods of data-mining and analyses of large datasets (machine learning) may help in parameterizing models as well as lead to new insights into the relationships between soil susceptibility to preferential flow and site attributes (climate, land uses, soil types).

  11. Advancing the understanding of autism disease mechanisms through genetics

    PubMed Central

    de la Torre-Ubieta, Luis; Won, Hyejung; Stein, Jason L; Geschwind, Daniel H

    2016-01-01

    Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. PMID:27050589

  12. Ranking of Business Process Simulation Software Tools with DEX/QQ Hierarchical Decision Model.

    PubMed

    Damij, Nadja; Boškoski, Pavle; Bohanec, Marko; Mileva Boshkoska, Biljana

    2016-01-01

    The omnipresent need for optimisation requires constant improvements of companies' business processes (BPs). Minimising the risk of inappropriate BP being implemented is usually performed by simulating the newly developed BP under various initial conditions and "what-if" scenarios. An effectual business process simulations software (BPSS) is a prerequisite for accurate analysis of an BP. Characterisation of an BPSS tool is a challenging task due to the complex selection criteria that includes quality of visual aspects, simulation capabilities, statistical facilities, quality reporting etc. Under such circumstances, making an optimal decision is challenging. Therefore, various decision support models are employed aiding the BPSS tool selection. The currently established decision support models are either proprietary or comprise only a limited subset of criteria, which affects their accuracy. Addressing this issue, this paper proposes a new hierarchical decision support model for ranking of BPSS based on their technical characteristics by employing DEX and qualitative to quantitative (QQ) methodology. Consequently, the decision expert feeds the required information in a systematic and user friendly manner. There are three significant contributions of the proposed approach. Firstly, the proposed hierarchical model is easily extendible for adding new criteria in the hierarchical structure. Secondly, a fully operational decision support system (DSS) tool that implements the proposed hierarchical model is presented. Finally, the effectiveness of the proposed hierarchical model is assessed by comparing the resulting rankings of BPSS with respect to currently available results.

  13. Modelling Glacial Lake Outburst Floods: Key Considerations and Challenges Posed By Climatic Change

    NASA Astrophysics Data System (ADS)

    Westoby, M.

    2014-12-01

    The number and size of moraine-dammed supraglacial and proglacial lakes is increasing as a result of contemporary climatic change. Moraine-dammed lakes are capable of impounding volumes of water in excess of 107 m3, and often represent a very real threat to downstream communities and infrastructure, should the bounding moraine fail and produce a catastrophic Glacial Lake Outburst Flood (GLOF). Modelling the individual components of a GLOF, including a triggering event, the complex dam-breaching process and downstream propagation of the flood is incredibly challenging, not least because direct observation and instrumentation of such high-magnitude flows is virtually impossible. We briefly review the current state-of-the-art in numerical GLOF modelling, with a focus on the theoretical and computational challenges associated with reconstructing or predicting GLOF dynamics in the face of rates of cryospheric change that have no historical precedent, as well as various implications for researchers and professionals tasked with the production of hazard maps and disaster mitigation strategies.

  14. Effect of Ganoderma lucidum on pollen-induced biphasic nasal blockage in a guinea pig model of allergic rhinitis.

    PubMed

    Mizutani, Nobuaki; Nabe, Takeshi; Shimazu, Masaji; Yoshino, Shin; Kohno, Shigekatsu

    2012-03-01

    Ganoderma lucidum (GL), an oriental medical mushroom, has been used in Asia for the prevention and treatment of a variety of diseases. However, the effect of GL on allergic rhinitis has not been well defined. The current study describes the inhibitory effect of GL on the biphasic nasal blockage and nasal hyperresponsiveness induced by repeated antigen challenge in a guinea pig model of allergic rhinitis. Intranasally sensitized guinea pigs were repeatedly challenged by inhalation of Japanese cedar pollen once every week. Ganoderma lucidum was orally administered once daily for 8 weeks from the time before the first challenge. The treatment with GL dose-dependently inhibited the early and late phase nasal blockage at the fifth to ninth antigen challenges. Furthermore, nasal hyperresponsiveness to intranasally applied leukotriene D₄ on 2 days after the eighth antigen challenge was also inhibited by the treatment with GL. However, Cry j 1-specific IgE antibody production was not affected by the treatment. In conclusion, we demonstrated that the pollen-induced biphasic nasal blockage and nasal hyperresponsiveness were suppressed by the daily treatment with GL in the guinea pig model of allergic rhinitis. These results suggest that GL may be a useful therapeutic drug for treating patients with allergic rhinitis. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Evaluation of the impacts of climate change on disease vectors through ecological niche modelling.

    PubMed

    Carvalho, B M; Rangel, E F; Vale, M M

    2017-08-01

    Vector-borne diseases are exceptionally sensitive to climate change. Predicting vector occurrence in specific regions is a challenge that disease control programs must meet in order to plan and execute control interventions and climate change adaptation measures. Recently, an increasing number of scientific articles have applied ecological niche modelling (ENM) to study medically important insects and ticks. With a myriad of available methods, it is challenging to interpret their results. Here we review the future projections of disease vectors produced by ENM, and assess their trends and limitations. Tropical regions are currently occupied by many vector species; but future projections indicate poleward expansions of suitable climates for their occurrence and, therefore, entomological surveillance must be continuously done in areas projected to become suitable. The most commonly applied methods were the maximum entropy algorithm, generalized linear models, the genetic algorithm for rule set prediction, and discriminant analysis. Lack of consideration of the full-known current distribution of the target species on models with future projections has led to questionable predictions. We conclude that there is no ideal 'gold standard' method to model vector distributions; researchers are encouraged to test different methods for the same data. Such practice is becoming common in the field of ENM, but still lags behind in studies of disease vectors.

  16. Engineering microbial electrocatalysis for chemical and fuel production.

    PubMed

    Rosenbaum, Miriam A; Henrich, Alexander W

    2014-10-01

    In many biotechnological areas, metabolic engineering and synthetic biology have become core technologies for biocatalyst development. Microbial electrocatalysis for biochemical and fuel production is still in its infancy and reactions rates and the product spectrum are currently very low. Therefore, molecular engineering strategies will be crucial for the advancement and realization of many new bioproduction routes using electroactive microorganisms. The complex and unresolved biochemistry and physiology of extracellular electron transfer and the lack of molecular tools for these new non-model hosts for genetic engineering constitute the major challenges for this effort. This review is providing an insight into the current status, challenges and promising approaches of pathway engineering for microbial electrocatalysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Toward a therapy for mitochondrial disease

    PubMed Central

    Viscomi, Carlo

    2016-01-01

    Mitochondrial disorders are a group of genetic diseases affecting the energy-converting process of oxidative phosphorylation. The extreme variability of symptoms, organ involvement, and clinical course represent a challenge to the development of effective therapeutic interventions. However, new possibilities have recently been emerging from studies in model organisms and awaiting verification in humans. I will discuss here the most promising experimental approaches and the challenges we face to translate them into the clinics. The current clinical trials will also be briefly reviewed. PMID:27911730

  18. A Framework for Reliability and Safety Analysis of Complex Space Missions

    NASA Technical Reports Server (NTRS)

    Evans, John W.; Groen, Frank; Wang, Lui; Austin, Rebekah; Witulski, Art; Mahadevan, Nagabhushan; Cornford, Steven L.; Feather, Martin S.; Lindsey, Nancy

    2017-01-01

    Long duration and complex mission scenarios are characteristics of NASA's human exploration of Mars, and will provide unprecedented challenges. Systems reliability and safety will become increasingly demanding and management of uncertainty will be increasingly important. NASA's current pioneering strategy recognizes and relies upon assurance of crew and asset safety. In this regard, flexibility to develop and innovate in the emergence of new design environments and methodologies, encompassing modeling of complex systems, is essential to meet the challenges.

  19. The Use of Dynamic Stochastic Social Behavior Models to Produce Likelihood Functions for Risk Modeling of Proliferation and Terrorist Attacks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, Jonathan; Thompson, Sandra E.; Brothers, Alan J.

    The ability to estimate the likelihood of future events based on current and historical data is essential to the decision making process of many government agencies. Successful predictions related to terror events and characterizing the risks will support development of options for countering these events. The predictive tasks involve both technical and social component models. The social components have presented a particularly difficult challenge. This paper outlines some technical considerations of this modeling activity. Both data and predictions associated with the technical and social models will likely be known with differing certainties or accuracies – a critical challenge is linkingmore » across these model domains while respecting this fundamental difference in certainty level. This paper will describe the technical approach being taken to develop the social model and identification of the significant interfaces between the technical and social modeling in the context of analysis of diversion of nuclear material.« less

  20. Implementation of the Strengths Model at an area mental health service.

    PubMed

    Chopra, Prem; Hamilton, Bridget; Castle, David; Smith, Jenny; Mileshkin, Cris; Deans, Michael; Wynne, Brad; Prigg, Glenn; Toomey, Nigel; Wilson, Michael

    2009-06-01

    The objectives of this paper are to provide an overview of recovery-focused models of care and discuss the implementation of the Strengths Model at St. Vincent's Mental Health Melbourne (SVMH), Victoria, Australia. The implementation of the Strengths Model at SVMH is discussed with particular emphasis on the process of implementation, service implications, practical challenges and dilemmas that have arisen, and proposed evaluation. Recovery-focused care is feasible and can enhance current practice of mental health services.

  1. An Agent Based Collaborative Simplification of 3D Mesh Model

    NASA Astrophysics Data System (ADS)

    Wang, Li-Rong; Yu, Bo; Hagiwara, Ichiro

    Large-volume mesh model faces the challenge in fast rendering and transmission by Internet. The current mesh models obtained by using three-dimensional (3D) scanning technology are usually very large in data volume. This paper develops a mobile agent based collaborative environment on the development platform of mobile-C. Communication among distributed agents includes grasping image of visualized mesh model, annotation to grasped image and instant message. Remote and collaborative simplification can be efficiently conducted by Internet.

  2. Meeting the challenges of case management with remote patient monitoring technology.

    PubMed

    Cherry, J C; Colliflower, S J; Tsiperfal, A

    2000-01-01

    The article presents an overview of some of the current trends in health care and the challenges faced by nurse case managers who are providing disease management services. It discusses some of the emerging technologies available today for innovative case management. In particular, this article describes a program run by a healthcare system in Sacramento, California that uses an Internet-based technology to enhance their nurse case management model. The article demonstrates how the Health Hero platform enables interactive communication between nurse case managers and their patients, thereby meeting some of the challenges the nurse case managers are faced with in the modern disease-management world.

  3. Spectral response, dark current, and noise analyses in resonant tunneling quantum dot infrared photodetectors.

    PubMed

    Jahromi, Hamed Dehdashti; Mahmoodi, Ali; Sheikhi, Mohammad Hossein; Zarifkar, Abbas

    2016-10-20

    Reduction of dark current at high-temperature operation is a great challenge in conventional quantum dot infrared photodetectors, as the rate of thermal excitations resulting in the dark current increases exponentially with temperature. A resonant tunneling barrier is the best candidate for suppression of dark current, enhancement in signal-to-noise ratio, and selective extraction of different wavelength response. In this paper, we use a physical model developed by the authors recently to design a proper resonant tunneling barrier for quantum infrared photodetectors and to study and analyze the spectral response of these devices. The calculated transmission coefficient of electrons by this model and its dependency on bias voltage are in agreement with experimental results. Furthermore, based on the calculated transmission coefficient, the dark current of a quantum dot infrared photodetector with a resonant tunneling barrier is calculated and compared with the experimental data. The validity of our model is proven through this comparison. Theoretical dark current by our model shows better agreement with the experimental data and is more accurate than the previously developed model. Moreover, noise in the device is calculated. Finally, the effect of different parameters, such as temperature, size of quantum dots, and bias voltage, on the performance of the device is simulated and studied.

  4. Integrated Experiential Education: Definitions and a Conceptual Model

    ERIC Educational Resources Information Center

    Fenton, Lara; Gallant, Karen

    2016-01-01

    Universities are currently embracing community engagement strategies to increase opportunities for student learning in community settings such as community organizations. Experiential learning is often touted as the pedagogy underlying such experiences. We undertook a research project exploring the challenges and benefits for students and faculty…

  5. Challenges in Designing a National Surveillance Program for Inflammatory Bowel Disease in the United States

    PubMed Central

    Long, Millie D.; Hutfless, Susan; Kappelman, Michael D.; Khalili, Hamed; Kaplan, Gil; Bernstein, Charles N.; Colombel, Jean Frederic; Herrinton, Lisa; Velayos, Fernando; Loftus, Edward V.; Nguyen, Geoffrey C.; Ananthakrishnan, Ashwin N.; Sonnenberg, Amnon; Chan, Andrew; Sandler, Robert S.; Atreja, Ashish; Shah, Samir A.; Rothman, Kenneth; Leleiko, Neal S.; Bright, Renee; Boffetta, Paolo; Myers, Kelly D.; Sands, Bruce E.

    2015-01-01

    This review describes the history of US government funding for surveillance programs in IBD, provides current estimates of the incidence and prevalence of inflammatory bowel diseases (IBD) in the United States (US), and enumerates a number of challenges faced by current and future IBD surveillance programs. A rationale for expanding the focus of IBD surveillance beyond counts of incidence and prevalence, in order to provide a greater understanding of the burden of IBD, disease etiology and pathogenesis, is provided. Lessons learned from other countries are summarized, as well as potential resources that may be used to optimize a new form of IBD surveillance in the US. A consensus recommendation on the goals and available resources for a new model for disease surveillance are provided. This new model should focus upon “surveillance of the burden of disease,” including 1) natural history of disease and 2) outcomes and complications of the disease and/or treatments. PMID:24280882

  6. Current Challenges in Geothermal Reservoir Simulation

    NASA Astrophysics Data System (ADS)

    Driesner, T.

    2016-12-01

    Geothermal reservoir simulation has long been introduced as a valuable tool for geothermal reservoir management and research. Yet, the current generation of simulation tools faces a number of severe challenges, in particular in the application for novel types of geothermal resources such as supercritical reservoirs or hydraulic stimulation. This contribution reviews a number of key problems: Representing the magmatic heat source of high enthalpy resources in simulations. Current practice is representing the deeper parts of a high enthalpy reservoir by a heat flux or temperature boundary condition. While this is sufficient for many reservoir management purposes it precludes exploring the chances of very high enthalpy resources in the deepest parts of such systems as well as the development of reliable conceptual models. Recent 2D simulations with the CSMP++ simulation platform demonstrate the potential of explicitly including the heat source, namely for understanding supercritical resources. Geometrically realistic incorporation of discrete fracture networks in simulation. A growing number of simulation tools can, in principle, handle flow and heat transport in discrete fracture networks. However, solving the governing equations and representing the physical properties are often biased by introducing strongly simplifying assumptions. Including proper fracture mechanics in complex fracture network simulations remains an open challenge. Improvements of the simulating chemical fluid-rock interaction in geothermal reservoirs. Major improvements have been made towards more stable and faster numerical solvers for multicomponent chemical fluid rock interaction. However, the underlying thermodynamic models and databases are unable to correctly address a number of important regions in temperature-pressure-composition parameter space. Namely, there is currently no thermodynamic formalism to describe relevant chemical reactions in supercritical reservoirs. Overcoming this unsatisfactory situation requires fundamental research in high temperature physical chemistry rather than further numerical development.

  7. Defense AT&L (Volume 35, Number 6, November-December 2006)

    DTIC Science & Technology

    2006-12-01

    our view of reality is inherently unstable. That is, when we realize our current cultural preferences, frame- works, mental models , doctrines...manufacturing rules and procedures (con- trols). IDEF0 function modeling has since been adopted for other applications such as business process... negotiating busy intersections, and avoiding obstacles. The DARPA Grand Challenge Web site <http://www.darpa.mil/grandchallenge>is the primary resource for

  8. A pilot Virtual Observatory (pVO) for integrated catchment science - Demonstration of national scale modelling of hydrology and biogeochemistry (Invited)

    NASA Astrophysics Data System (ADS)

    Freer, J. E.; Bloomfield, J. P.; Johnes, P. J.; MacLeod, C.; Reaney, S.

    2010-12-01

    There are many challenges in developing effective and integrated catchment management solutions for hydrology and water quality issues. Such solutions should ideally build on current scientific evidence to inform policy makers and regulators and additionally allow stakeholders to take ownership of local and/or national issues, in effect bringing together ‘communities of practice’. A strategy being piloted in the UK as the Pilot Virtual Observatory (pVO), funded by NERC, is to demonstrate the use of cyber-infrastructure and cloud computing resources to investigate better methods of linking data and models and to demonstrate scenario analysis for research, policy and operational needs. The research will provide new ways the scientific and stakeholder communities come together to exploit current environmental information, knowledge and experience in an open framework. This poster presents the project scope and methodologies for the pVO work dealing with national modelling of hydrology and macro-nutrient biogeochemistry. We evaluate the strategies needed to robustly benchmark our current predictive capability of these resources through ensemble modelling. We explore the use of catchment similarity concepts to understand if national monitoring programs can inform us about the behaviour of catchments. We discuss the challenges to applying these strategies in an open access and integrated framework and finally we consider the future for such virtual observatory platforms for improving the way we iteratively improve our understanding of catchment science.

  9. Systematic Analysis of Challenge-Driven Improvements in Molecular Prognostic Models for Breast Cancer

    PubMed Central

    Margolin, Adam A.; Bilal, Erhan; Huang, Erich; Norman, Thea C.; Ottestad, Lars; Mecham, Brigham H.; Sauerwine, Ben; Kellen, Michael R.; Mangravite, Lara M.; Furia, Matthew D.; Vollan, Hans Kristian Moen; Rueda, Oscar M.; Guinney, Justin; Deflaux, Nicole A.; Hoff, Bruce; Schildwachter, Xavier; Russnes, Hege G.; Park, Daehoon; Vang, Veronica O.; Pirtle, Tyler; Youseff, Lamia; Citro, Craig; Curtis, Christina; Kristensen, Vessela N.; Hellerstein, Joseph; Friend, Stephen H.; Stolovitzky, Gustavo; Aparicio, Samuel; Caldas, Carlos; Børresen-Dale, Anne-Lise

    2013-01-01

    Although molecular prognostics in breast cancer are among the most successful examples of translating genomic analysis to clinical applications, optimal approaches to breast cancer clinical risk prediction remain controversial. The Sage Bionetworks–DREAM Breast Cancer Prognosis Challenge (BCC) is a crowdsourced research study for breast cancer prognostic modeling using genome-scale data. The BCC provided a community of data analysts with a common platform for data access and blinded evaluation of model accuracy in predicting breast cancer survival on the basis of gene expression data, copy number data, and clinical covariates. This approach offered the opportunity to assess whether a crowdsourced community Challenge would generate models of breast cancer prognosis commensurate with or exceeding current best-in-class approaches. The BCC comprised multiple rounds of blinded evaluations on held-out portions of data on 1981 patients, resulting in more than 1400 models submitted as open source code. Participants then retrained their models on the full data set of 1981 samples and submitted up to five models for validation in a newly generated data set of 184 breast cancer patients. Analysis of the BCC results suggests that the best-performing modeling strategy outperformed previously reported methods in blinded evaluations; model performance was consistent across several independent evaluations; and aggregating community-developed models achieved performance on par with the best-performing individual models. PMID:23596205

  10. Current and emerging business models in the health care information technology industry: a view from wall street.

    PubMed

    Frank, Seth

    2003-01-01

    When we think about health care IT, we don't just think about clinical automation with the movement to computerized physician order entry (CPOE), but also the need to upgrade legacy financial and administrative systems to interact with clinical systems. Technology acceptance by physicians remains low, and computer use by physicians for data entry and analysis remains minimal. We expect this trend to change, and expect increased automation to represent gradual change. The HCIT space is dynamic, with many opportunities, but also many challenges. The unique nature of the end market buyers, existing business models, and nature of the technology makes this a challenging but dynamic area for equity investment.

  11. Electricity Market Games: How Agent-Based Modeling Can Help under High Penetrations of Variable Generation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gallo, Giulia

    Integrating increasingly high levels of variable generation in U.S. electricity markets requires addressing not only power system and grid modeling challenges but also an understanding of how market participants react and adapt to them. Key elements of current and future wholesale power markets can be modeled using an agent-based approach, which may prove to be a useful paradigm for researchers studying and planning for power systems of the future.

  12. Visualization, documentation, analysis, and communication of large scale gene regulatory networks

    PubMed Central

    Longabaugh, William J.R.; Davidson, Eric H.; Bolouri, Hamid

    2009-01-01

    Summary Genetic regulatory networks (GRNs) are complex, large-scale, and spatially and temporally distributed. These characteristics impose challenging demands on computational GRN modeling tools, and there is a need for custom modeling tools. In this paper, we report on our ongoing development of BioTapestry, an open source, freely available computational tool designed specifically for GRN modeling. We also outline our future development plans, and give some examples of current applications of BioTapestry. PMID:18757046

  13. The Mechanics of Embodiment: A Dialog on Embodiment and Computational Modeling

    PubMed Central

    Pezzulo, Giovanni; Barsalou, Lawrence W.; Cangelosi, Angelo; Fischer, Martin H.; McRae, Ken; Spivey, Michael J.

    2011-01-01

    Embodied theories are increasingly challenging traditional views of cognition by arguing that conceptual representations that constitute our knowledge are grounded in sensory and motor experiences, and processed at this sensorimotor level, rather than being represented and processed abstractly in an amodal conceptual system. Given the established empirical foundation, and the relatively underspecified theories to date, many researchers are extremely interested in embodied cognition but are clamoring for more mechanistic implementations. What is needed at this stage is a push toward explicit computational models that implement sensorimotor grounding as intrinsic to cognitive processes. In this article, six authors from varying backgrounds and approaches address issues concerning the construction of embodied computational models, and illustrate what they view as the critical current and next steps toward mechanistic theories of embodiment. The first part has the form of a dialog between two fictional characters: Ernest, the “experimenter,” and Mary, the “computational modeler.” The dialog consists of an interactive sequence of questions, requests for clarification, challenges, and (tentative) answers, and touches the most important aspects of grounded theories that should inform computational modeling and, conversely, the impact that computational modeling could have on embodied theories. The second part of the article discusses the most important open challenges for embodied computational modeling. PMID:21713184

  14. Animal models of protein allergenicity: potential benefits, pitfalls and challenges.

    PubMed

    Dearman, R J; Kimber, I

    2009-04-01

    Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross-react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end-points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge-induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.

  15. Testing Transitivity of Preferences on Two-Alternative Forced Choice Data

    PubMed Central

    Regenwetter, Michel; Dana, Jason; Davis-Stober, Clintin P.

    2010-01-01

    As Duncan Luce and other prominent scholars have pointed out on several occasions, testing algebraic models against empirical data raises difficult conceptual, mathematical, and statistical challenges. Empirical data often result from statistical sampling processes, whereas algebraic theories are nonprobabilistic. Many probabilistic specifications lead to statistical boundary problems and are subject to nontrivial order constrained statistical inference. The present paper discusses Luce's challenge for a particularly prominent axiom: Transitivity. The axiom of transitivity is a central component in many algebraic theories of preference and choice. We offer the currently most complete solution to the challenge in the case of transitivity of binary preference on the theory side and two-alternative forced choice on the empirical side, explicitly for up to five, and implicitly for up to seven, choice alternatives. We also discuss the relationship between our proposed solution and weak stochastic transitivity. We recommend to abandon the latter as a model of transitive individual preferences. PMID:21833217

  16. Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems.

    PubMed

    Vaquero, Juan José; Kinahan, Paul

    2015-01-01

    Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges.

  17. Ethical Challenges in Psychiatric Administration and Leadership.

    PubMed

    Moffic, H Steven; Saeed, Sy Atezaz; Silver, Stuart; Koh, Steve

    2015-09-01

    As with all professional ethical principles, those in psychiatry have to evolve over time and societal changes. The current ethical challenges for psychiatric administration and leadership, especially regarding for-profit managed care, need updated solutions. One solution resides in the development by the American Association of Psychiatric Administrators (AAPA) of the first set of ethical principles designed specifically for psychiatric administrators. These principles build on prior Psychological Theories of leadership, such as those of Freud, Kernberg, and Kohut. Supplementing these theories are the actual real life models of psychiatrist leadership as depicted in the memoirs of various psychiatrists. Appreciating these principles, theories, and models may help emerging leaders to better recognize the importance of ethical challenges. A conclusion is that psychiatrists should have the potential to assume more successful leadership positions once again. In such positions, making the skills and well-being of all in the organization seems now to be the foremost ethical priority.

  18. A multi-domain trust management model for supporting RFID applications of IoT

    PubMed Central

    Li, Feng

    2017-01-01

    The use of RFID technology in complex and distributed environments often leads to a multi-domain RFID system, in which trust establishment among entities from heterogeneous domains without past interaction or prior agreed policy, is a challenge. The current trust management mechanisms in the literature do not meet the specific requirements in multi-domain RFID systems. Therefore, this paper analyzes the special challenges on trust management in multi-domain RFID systems, and identifies the implications and the requirements of the challenges on the solutions to the trust management of multi-domain RFID systems. A multi-domain trust management model is proposed, which provides a hierarchical trust management framework include a diversity of trust evaluation and establishment approaches. The simulation results and analysis show that the proposed method has excellent ability to deal with the trust relationships, better security, and higher accuracy rate. PMID:28708855

  19. A multi-domain trust management model for supporting RFID applications of IoT.

    PubMed

    Wu, Xu; Li, Feng

    2017-01-01

    The use of RFID technology in complex and distributed environments often leads to a multi-domain RFID system, in which trust establishment among entities from heterogeneous domains without past interaction or prior agreed policy, is a challenge. The current trust management mechanisms in the literature do not meet the specific requirements in multi-domain RFID systems. Therefore, this paper analyzes the special challenges on trust management in multi-domain RFID systems, and identifies the implications and the requirements of the challenges on the solutions to the trust management of multi-domain RFID systems. A multi-domain trust management model is proposed, which provides a hierarchical trust management framework include a diversity of trust evaluation and establishment approaches. The simulation results and analysis show that the proposed method has excellent ability to deal with the trust relationships, better security, and higher accuracy rate.

  20. Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems

    PubMed Central

    Vaquero, Juan José; Kinahan, Paul

    2017-01-01

    Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges. PMID:26643024

  1. Predicting the resilience and recovery of aquatic systems: A framework for model evolution within environmental observatories

    NASA Astrophysics Data System (ADS)

    Hipsey, Matthew R.; Hamilton, David P.; Hanson, Paul C.; Carey, Cayelan C.; Coletti, Janaine Z.; Read, Jordan S.; Ibelings, Bas W.; Valesini, Fiona J.; Brookes, Justin D.

    2015-09-01

    Maintaining the health of aquatic systems is an essential component of sustainable catchment management, however, degradation of water quality and aquatic habitat continues to challenge scientists and policy-makers. To support management and restoration efforts aquatic system models are required that are able to capture the often complex trajectories that these systems display in response to multiple stressors. This paper explores the abilities and limitations of current model approaches in meeting this challenge, and outlines a strategy based on integration of flexible model libraries and data from observation networks, within a learning framework, as a means to improve the accuracy and scope of model predictions. The framework is comprised of a data assimilation component that utilizes diverse data streams from sensor networks, and a second component whereby model structural evolution can occur once the model is assessed against theoretically relevant metrics of system function. Given the scale and transdisciplinary nature of the prediction challenge, network science initiatives are identified as a means to develop and integrate diverse model libraries and workflows, and to obtain consensus on diagnostic approaches to model assessment that can guide model adaptation. We outline how such a framework can help us explore the theory of how aquatic systems respond to change by bridging bottom-up and top-down lines of enquiry, and, in doing so, also advance the role of prediction in aquatic ecosystem management.

  2. Data sharing in the ag community - what are current challenges, benefits, and opportunities

    USDA-ARS?s Scientific Manuscript database

    The model for building agronomic science today and into the future to meet global food demands with limited resources will be through public-private data acquisition, sharing, and collaborative analysis. The public perspective focuses on preserving natural resources. The private perspective focuses ...

  3. The Talent Search Model: Past, Present, and Future

    ERIC Educational Resources Information Center

    Swiatek, Mary Ann

    2007-01-01

    Typical standardized achievement tests cannot provide accurate information about gifted students' abilities because they are not challenging enough for such students. Talent searches solve this problem through above-level testing--using tests designed for older students to raise the ceiling for younger, gifted students. Currently, talent search…

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    J. Carmack; L. Braase; F. Goldner

    The mission of the Advanced Fuels Campaign (AFC) is to perform Research, Development, and Demonstration (RD&D) activities for advanced fuel forms (including cladding) to enhance the performance and safety of the nation’s current and future reactors, enhance proliferation resistance of nuclear fuel, effectively utilize nuclear energy resources, and address the longer-term waste management challenges. This includes development of a state of the art Research and Development (R&D) infrastructure to support the use of a “goal oriented science based approach.” AFC uses a “goal oriented, science based approach” aimed at a fundamental understanding of fuel and cladding fabrication methods and performancemore » under irradiation, enabling the pursuit of multiple fuel forms for future fuel cycle options. This approach includes fundamental experiments, theory, and advanced modeling and simulation. One of the most challenging aspects of AFC is the management, integration, and coordination of major R&D activities across multiple organizations. AFC interfaces and collaborates with Fuel Cycle Technologies (FCT) campaigns, universities, industry, various DOE programs and laboratories, federal agencies (e.g., Nuclear Regulatory Commission [NRC]), and international organizations. Key challenges are the development of fuel technologies to enable major increases in fuel performance (safety, reliability, power and burnup) beyond current technologies, and development of characterization methods and predictive fuel performance models to enable more efficient development and licensing of advanced fuels. Challenged with the research and development of fuels for two different reactor technology platforms, AFC targeted transmutation fuel development and focused ceramic fuel development for Advanced LWR Fuels.« less

  5. Numerical simulations of merging black holes for gravitational-wave astronomy

    NASA Astrophysics Data System (ADS)

    Lovelace, Geoffrey

    2014-03-01

    Gravitational waves from merging binary black holes (BBHs) are among the most promising sources for current and future gravitational-wave detectors. Accurate models of these waves are necessary to maximize the number of detections and our knowledge of the waves' sources; near the time of merger, the waves can only be computed using numerical-relativity simulations. For optimal application to gravitational-wave astronomy, BBH simulations must achieve sufficient accuracy and length, and all relevant regions of the BBH parameter space must be covered. While great progress toward these goals has been made in the almost nine years since BBH simulations became possible, considerable challenges remain. In this talk, I will discuss current efforts to meet these challenges, and I will present recent BBH simulations produced using the Spectral Einstein Code, including a catalog of publicly available gravitational waveforms [black-holes.org/waveforms]. I will also discuss simulations of merging black holes with high mass ratios and with spins nearly as fast as possible, the most challenging regions of the BBH parameter space.

  6. [Productivity and academic assessment in the Brazilian public health field: challenges for Human and Social Sciences research].

    PubMed

    Bosi, Maria Lúcia Magalhães

    2012-12-01

    This article analyzes some challenges for knowledge output in the human and social sciences in the public health field, under the current academic assessment model in Brazil. The article focuses on the qualitative research approach in human and social sciences, analyzing its status in comparison to the other traditions vying for hegemony in the public health field, conjugating the dialogue with the literature, especially the propositions pertaining to the social fields present in the work of Pierre Bourdieu, with elements concerning the field's dynamics, including some empirical data. Challenges identified in the article include hurdles to interdisciplinary dialogue and equity in the production of knowledge, based on recognition of the founding place of human and social sciences in the public health field. The article discusses strategies to reshape the current correlation of forces among centers of knowledge in public health, especially those capable of impacting the committees and agendas that define the accumulation of symbolic and economic capital in the field.

  7. A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

    PubMed

    Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

    2015-04-01

    Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

  8. Perspectives on Creating Clinically Relevant Blast Models for Mild Traumatic Brain Injury and Post Traumatic Stress Disorder Symptoms

    PubMed Central

    Brenner, Lisa A.; Bahraini, Nazanin; Hernández, Theresa D.

    2012-01-01

    Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast) traumatic brain injury can be used to facilitate the development of clinically relevant blast models. PMID:22408635

  9. Animal models of binge drinking, current challenges to improve face validity.

    PubMed

    Jeanblanc, Jérôme; Rolland, Benjamin; Gierski, Fabien; Martinetti, Margaret P; Naassila, Mickael

    2018-05-05

    Binge drinking (BD), i.e., consuming a large amount of alcohol in a short period of time, is an increasing public health issue. Though no clear definition has been adopted worldwide the speed of drinking seems to be a keystone of this behavior. Developing relevant animal models of BD is a priority for gaining a better characterization of the neurobiological and psychobiological mechanisms underlying this dangerous and harmful behavior. Until recently, preclinical research on BD has been conducted mostly using forced administration of alcohol, but more recent studies used scheduled access to alcohol, to model more voluntary excessive intakes, and to achieve signs of intoxications that mimic the human behavior. The main challenges for future research are discussed regarding the need of good face validity, construct validity and predictive validity of animal models of BD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. The response to challenging behaviour by care staff: emotional responses, attributions of cause and observations of practice.

    PubMed

    Bailey, B A; Hare, D J; Hatton, C; Limb, K

    2006-03-01

    Previous studies have attempted to apply Weiner's attributional model of helping behaviour to care staff who work with service users with intellectual disabilities and challenging behaviours by using studies based on vignettes. The aims of the current study were to investigate the application of Weiner's model to 'real' service users with intellectual disabilities and challenging behaviours and to observe the care staff's actual responses to challenging behaviours displayed by service users. Also, to compare care staff attributions, emotions, optimism, willingness to help and observed helping behaviours for self-injurious behaviours in comparison to other forms of challenging behaviours. A total of 27 care staff completed two sets of measures, one set regarding a self-injurious behaviour and the other regarding other forms of challenging behaviour. An additional 16 staff completed one set of measures. The measures focused on care staff attributions, emotions, optimism and willingness to help. Also, 16 of the care staff were observed interacting with the service users to collect data regarding their responses to challenging behaviours. For both self-injurious behaviours and other forms of challenging behaviour, associations were found between the care staff internal, stable and uncontrollable attribution scores and care staff negative emotion scores. However, no associations were found between the care staff levels of emotion, optimism and willingness to help. Some associations were found between the care staff levels of willingness to help and observed helping behaviours. There were significant differences between the care staff attribution scores with higher scores being obtained for uncontrollable and stable attributions for other forms of challenging behaviours. No significant differences were found between the care staff emotions, optimism, willingness to help and observed helping behaviours. The results did not provide support for Weiner's attributional model of helping behaviour. However, a preliminary model of negative care staff behaviour was derived from the exploratory analyses completed. This model proposes that there are associations between internal, stable and uncontrollable attributions and negative emotions in care staff and also between negative emotions and negative behaviours displayed by care staff in response to the actions of service users.

  11. Predicting the resilience and recovery of aquatic systems: a framework for model evolution within environmental observatories

    USGS Publications Warehouse

    Hipsey, Matthew R.; Hamilton, David P.; Hanson, Paul C.; Carey, Cayelan C.; Coletti, Janaine Z; Read, Jordan S.; Ibelings, Bas W; Valensini, Fiona J; Brookes, Justin D

    2015-01-01

    Maintaining the health of aquatic systems is an essential component of sustainable catchmentmanagement, however, degradation of water quality and aquatic habitat continues to challenge scientistsand policy-makers. To support management and restoration efforts aquatic system models are requiredthat are able to capture the often complex trajectories that these systems display in response to multiplestressors. This paper explores the abilities and limitations of current model approaches in meeting this chal-lenge, and outlines a strategy based on integration of flexible model libraries and data from observationnetworks, within a learning framework, as a means to improve the accuracy and scope of model predictions.The framework is comprised of a data assimilation component that utilizes diverse data streams from sensornetworks, and a second component whereby model structural evolution can occur once the model isassessed against theoretically relevant metrics of system function. Given the scale and transdisciplinarynature of the prediction challenge, network science initiatives are identified as a means to develop and inte-grate diverse model libraries and workflows, and to obtain consensus on diagnostic approaches to modelassessment that can guide model adaptation. We outline how such a framework can help us explore thetheory of how aquatic systems respond to change by bridging bottom-up and top-down lines of enquiry,and, in doing so, also advance the role of prediction in aquatic ecosystem management.

  12. Informatics in clinical research in oncology: current state, challenges, and a future perspective.

    PubMed

    Chahal, Amar P S

    2011-01-01

    The informatics landscape of clinical trials in oncology has changed significantly in the last 10 years. The current state of the infrastructure for clinical trial management, execution, and data management is reviewed. The systems, their functionality, the users, and the standards available to researchers are discussed from the perspective of the oncologist-researcher. Challenges in complexity and in the processing of information are outlined. These challenges include the lack of communication and information-interchange between systems, the lack of simplified standards, and the lack of implementation and adherence to the standards that are available. The clinical toxicology criteria from the National Cancer Institute (CTCAE) are cited as a successful standard in oncology, and HTTP on the Internet is referenced for its simplicity. Differences in the management of information standards between industries are discussed. Possible future advances in oncology clinical research informatics are addressed. These advances include strategic policy review of standards and the implementation of actions to make standards free, ubiquitous, simple, and easily interpretable; the need to change from a local data-capture- or transaction-driven model to a large-scale data-interpretation model that provides higher value to the oncologist and the patient; and the need for information technology investment in a readily available digital educational model for clinical research in oncology that is customizable for individual studies. These new approaches, with changes in information delivery to mobile platforms, will set the stage for the next decade in clinical research informatics.

  13. Enhancing metaproteomics-The value of models and defined environmental microbial systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herbst, Florian-Alexander; Lünsmann, Vanessa; Kjeldal, Henrik

    Metaproteomicsthe large-scale characterization of the entire protein complement of environmental microbiota at a given point in timehas provided new features to study complex microbial communities in order to unravel these black boxes. Some new technical challenges arose that were not an issue for classical proteome analytics before that could be tackled by the application of different model systems. Here, we review different current and future model systems for metaproteome analysis. We introduce model systems for clinical and biotechnological research questions including acid mine drainage, anaerobic digesters, and activated sludge, following a short introduction to microbial communities and metaproteomics. Model systemsmore » are useful to evaluate the challenges encountered within (but not limited to) metaproteomics, including species complexity and coverage, biomass availability, or reliable protein extraction. Moreover, the implementation of model systems can be considered as a step forward to better understand microbial community responses and ecological functions of single member organisms. In the future, improvements are necessary to fully explore complex environmental systems by metaproteomics.« less

  14. Enhancing metaproteomics-The value of models and defined environmental microbial systems

    DOE PAGES

    Herbst, Florian-Alexander; Lünsmann, Vanessa; Kjeldal, Henrik; ...

    2016-01-21

    Metaproteomicsthe large-scale characterization of the entire protein complement of environmental microbiota at a given point in timehas provided new features to study complex microbial communities in order to unravel these black boxes. Some new technical challenges arose that were not an issue for classical proteome analytics before that could be tackled by the application of different model systems. Here, we review different current and future model systems for metaproteome analysis. We introduce model systems for clinical and biotechnological research questions including acid mine drainage, anaerobic digesters, and activated sludge, following a short introduction to microbial communities and metaproteomics. Model systemsmore » are useful to evaluate the challenges encountered within (but not limited to) metaproteomics, including species complexity and coverage, biomass availability, or reliable protein extraction. Moreover, the implementation of model systems can be considered as a step forward to better understand microbial community responses and ecological functions of single member organisms. In the future, improvements are necessary to fully explore complex environmental systems by metaproteomics.« less

  15. Automatic building information model query generation

    DOE PAGES

    Jiang, Yufei; Yu, Nan; Ming, Jiang; ...

    2015-12-01

    Energy efficient building design and construction calls for extensive collaboration between different subfields of the Architecture, Engineering and Construction (AEC) community. Performing building design and construction engineering raises challenges on data integration and software interoperability. Using Building Information Modeling (BIM) data hub to host and integrate building models is a promising solution to address those challenges, which can ease building design information management. However, the partial model query mechanism of current BIM data hub collaboration model has several limitations, which prevents designers and engineers to take advantage of BIM. To address this problem, we propose a general and effective approachmore » to generate query code based on a Model View Definition (MVD). This approach is demonstrated through a software prototype called QueryGenerator. In conclusion, by demonstrating a case study using multi-zone air flow analysis, we show how our approach and tool can help domain experts to use BIM to drive building design with less labour and lower overhead cost.« less

  16. Challenges to modeling the Sun-Earth System: A Workshop Summary

    NASA Technical Reports Server (NTRS)

    Spann, James F.

    2006-01-01

    This special issue of the Journal of' Atmospheric and Solar-Terrestrial Physics is a compilation of 23 papers presented at The 2004 Huntsville Modeling Workshop: Challenges to Modeling thc San-Earth System held in Huntsville, AB on October 18-22, 2004. The title of the workshop appropriately captures the theme of what was presented and discussed by the 120 participants. Currently, end-to-end modeling of the Sun-Earth system is a major goal of the National Space Weather and NASA living with a star (LWS) programs. While profound advances have been made in modeling isolated regions of the Sun-Earth system, minimal progress has been achieved in modeling the end-to-end system. The transfer of mass, energy and momentum through the coupled Sun-Earth system spans a wide range of scales inn time and space. The uncertainty in the underlying physics responsible for coupling contiguous regions of the Sun-Earth system is recognized as a significant barrier to progress

  17. Automatic building information model query generation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jiang, Yufei; Yu, Nan; Ming, Jiang

    Energy efficient building design and construction calls for extensive collaboration between different subfields of the Architecture, Engineering and Construction (AEC) community. Performing building design and construction engineering raises challenges on data integration and software interoperability. Using Building Information Modeling (BIM) data hub to host and integrate building models is a promising solution to address those challenges, which can ease building design information management. However, the partial model query mechanism of current BIM data hub collaboration model has several limitations, which prevents designers and engineers to take advantage of BIM. To address this problem, we propose a general and effective approachmore » to generate query code based on a Model View Definition (MVD). This approach is demonstrated through a software prototype called QueryGenerator. In conclusion, by demonstrating a case study using multi-zone air flow analysis, we show how our approach and tool can help domain experts to use BIM to drive building design with less labour and lower overhead cost.« less

  18. A New Regulatory Policy for FTTx-Based Next-Generation Access Networks

    NASA Astrophysics Data System (ADS)

    Makarovič, Boštjan

    2013-07-01

    This article critically assesses the latest European Commission policies in relation to next-generation access investment that put focus on regulated prices and relaxing of wholesale access obligations. Pointing at the vital socio-legal and economic arguments, it further challenges the assumptions of the current EU regulatory framework and calls for a more contractual utility-based model of regulation instead of the current system that overly relies on market-driven infrastructure-based competition.

  19. Gradient and shim technologies for ultra high field MRI

    PubMed Central

    Winkler, Simone A.; Schmitt, Franz; Landes, Hermann; DeBever, Josh; Wade, Trevor; Alejski, Andrew

    2017-01-01

    Ultra High Field (UHF) MRI requires improved gradient and shim performance to fully realize the promised gains (SNR as well as spatial, spectral, diffusion resolution) that higher main magnetic fields offer. Both the more challenging UHF environment by itself, as well as the higher currents used in high performance coils, require a deeper understanding combined with sophisticated engineering modeling and construction, to optimize gradient and shim hardware for safe operation and for highest image quality. This review summarizes the basics of gradient and shim technologies, and outlines a number of UHF-related challenges and solutions. In particular, Lorentz forces, vibroacoustics, eddy currents, and peripheral nerve stimulation are discussed. Several promising UHF-relevant gradient concepts are described, including insertable gradient coils aimed at higher performance neuroimaging. PMID:27915120

  20. A two particle hidden sector and the oscillations with photons

    NASA Astrophysics Data System (ADS)

    Alvarez, Pedro D.; Arias, Paola; Maldonado, Carlos

    2018-01-01

    We present a detailed study of the oscillations and optical properties for vacuum, in a model for the dark sector that contains axion-like particles and hidden photons. We provide bounds for the couplings versus the mass, using current results from ALPS-I and PVLAS. We also discuss the challenges for the detection of models with more than one hidden particle in light shining trough wall-like experiments.

  1. Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement

    USDA-ARS?s Scientific Manuscript database

    To address the multiple challenges to food security posed by global climate change, population growth and rising incomes, plant breeders are developing new crop varieties that can enhance both agricultural productivity and environmental sustainability. Current breeding practices, however, are unable...

  2. DEVELOPMENT OF AN URBAN FOOD LEADERSHIP COOP IN SUPPORT OF A LOCAL FOOD SYSTEM

    EPA Science Inventory

    A need shared by all communities is a clean environment that supports a sustainable food system and promotes human health. The current food system does not model environmental, social, or economic sustainability. Therefore, the challenge is to develop and support a new food ...

  3. Toward an Engagement Model of Institutional Advancement at Public Colleges and Universities

    ERIC Educational Resources Information Center

    Weerts, David J.

    2007-01-01

    Enrollment pressures, unstable state appropriations, and increased public scrutiny about higher education's commitment to serving societal needs have created significant challenges for university advancement professionals at public colleges and universities in the United States. In this paper, I describe how current responses to these challenges…

  4. Critical Supports for Secondary Educators in Common Core State Standard Implementation

    ERIC Educational Resources Information Center

    Ruchti, Wendy P.; Jenkins, Susan J.; Agamba, Joachim

    2013-01-01

    Teacher professional development (PD) is a complex, ongoing challenge as educational systems attempt to deliver excellent programming in pursuit of increased student achievement (Opfer and Pedder 2011). This article examines Idaho Total Instructional Alignment (TIA), a model for teacher PD that is currently being utilized in secondary schools…

  5. Training Child Welfare Workers from an Intersectional Cultural Humility Perspective: A Paradigm Shift

    ERIC Educational Resources Information Center

    Ortega, Robert M.; Faller, Kathleen Coulborn

    2011-01-01

    The increasing diversity of the populations encountered and served by child welfare workers challenges cultural competence models. Current concerns focus on the unintentional over-emphasis on shared group characteristics, undervaluing unique differences of individuals served, and privileging worker expertise about the client's culture, thereby…

  6. Multidimensional Measurement of Situational Interest in Physical Education: Application of Bifactor Exploratory Structural Equation Modeling

    ERIC Educational Resources Information Center

    Garn, Alex C.

    2017-01-01

    Multidimensional measurement is a common theme in motivation research because many constructs are conceptualized as having an overarching general factor (e.g., situational interest) and specific dimensions (e.g., attention demand, challenge, exploration intention, instant enjoyment, novelty). This review addresses current issues associated with…

  7. Simulating and Optimizing Preparative Protein Chromatography with ChromX

    ERIC Educational Resources Information Center

    Hahn, Tobias; Huuk, Thiemo; Heuveline, Vincent; Hubbuch, Ju¨rgen

    2015-01-01

    Industrial purification of biomolecules is commonly based on a sequence of chromatographic processes, which are adapted slightly to new target components, as the time to market is crucial. To improve time and material efficiency, modeling is increasingly used to determine optimal operating conditions, thus providing new challenges for current and…

  8. Effective Characteristics of Parish School Boards in the Archdiocese of Hartford

    ERIC Educational Resources Information Center

    Hoyt, Dale Raymond

    2012-01-01

    While the success of Catholic school education is well documented, significant challenges currently threaten the Church's educational apostolate. Faced with increasing deficits, dwindling enrollments, low salaries, and aged facilities, Catholic schools across the country are studying governance models that will ensure the long-term sustainability…

  9. Improving toxicity extrapolation using molecular sequence similarity: A case study of pyrethroids and the sodium ion channel

    EPA Science Inventory

    A significant challenge in ecotoxicology has been determining chemical hazards to species with limited or no toxicity data. Currently, extrapolation tools like U.S. EPA’s Web-based Interspecies Correlation Estimation (Web-ICE; www3.epa.gov/webice) models categorize toxicity...

  10. Evaluation of the Service Review Model with Performance Scorecards

    ERIC Educational Resources Information Center

    Szabo, Thomas G.; Williams, W. Larry; Rafacz, Sharlet D.; Newsome, William; Lydon, Christina A.

    2012-01-01

    The current study combined a management technique termed "Service Review" with performance scorecards to enhance staff and consumer behavior in a human service setting consisting of 11 supervisors and 56 front-line staff working with 9 adult consumers with challenging behaviors. Results of our intervention showed that service review and…

  11. Innovating Business Communication Courses in Oman: From Design to Implementation

    ERIC Educational Resources Information Center

    Dauletova, Victoria

    2016-01-01

    The article challenges the conventional formats applied by business and professional education in higher academic institutions in Oman. The shift from the current traditional educational paradigm to more effective and engaging approaches to instruction is proposed through the launch of an alternative teaching/learning model which aims at preparing…

  12. Risk: The Ethics of a Creative Curriculum

    ERIC Educational Resources Information Center

    Hargreaves, Janet

    2008-01-01

    Higher education in the UK espouses to develop intelligence and critical skills in undergraduates. To do this requires exposing students to challenge and thus risk. However, current models of quality assurance are risk-averse and thus potentially limit the scope of creative learning and teaching strategies. Using two case studies, this paper…

  13. Future socio-economic impacts and vulnerabilities

    Treesearch

    Balgis Osman-Elasha; Neil Adger; Maria Brockhaus; Carol J. Pierce Colfer; Brent Sohngen; Tallaat Dafalla; Linda A. Joyce; Nkem Johnson; Carmenza Robledo

    2009-01-01

    The projected impacts of climate change are significant, and despite the uncertainties associated with current climate and ecosystem model projections, the associated changes in the provision of forest ecosystem services are expected to be substantial in many parts of the world. These impacts will present significant social and economic challenges for affected...

  14. Predictive Modeling of Apical Toxicity Endpoints Using Data From ToxCast

    EPA Science Inventory

    The US EPA and other regulatory agencies face a daunting challenge of evaluating potential toxicity for tens of thousands of environmental chemicals about which little is currently known. The EPA’s ToxCast program is testing a novel approach to this problem by screening compounds...

  15. [A new prison health care model: the experience of the Basque Country].

    PubMed

    Zulaika, D; Etxeandia, P; Bengoa, A; Caminos, J; Arroyo-Cobo, J M

    2012-02-01

    A year after the transfer of prison health care functions and services from the State Administration to the Autonomous Community of the Basque Country, the process up to completion of the transfer, the current status of the transferred services and remaining challenges are described.

  16. Entrepreneurship management in health services: an integrative model.

    PubMed

    Guo, Kristina L

    2006-01-01

    This research develops an integrated systems model of entrepreneurship management as a method for achieving health care organizational survival and growth. Specifically, it analyzes current health care environment challenges, identifies roles of managers and discusses organizational theories that are relevant to the health care environment, outlines the role of entrepreneurship in health care, and describes the entrepreneurial manager in the entrepreneurial management process to produce desirable organizational outcomes. The study concludes that as current health care environment continues to show intense competition, entrepreneurial managers are responsible for creating innovations, managing change, investing in resources, and recognizing opportunities in the environment to increase organizational viability.

  17. Experimental testing of scattering polarization models

    NASA Astrophysics Data System (ADS)

    Li, Wenxian; Casini, Roberto; Tomczyk, Steven; Landi Degl'Innocenti, Egidio; Marsell, Brandan

    2018-06-01

    We realized a laboratory experiment to study the polarization of the Na I doublet at 589.3 nm, in the presence of a magnetic field. The purpose of the experiment is to test the theory of scattering polarization for illumination conditions typical of astrophysical plasmas. This work was stimulated by solar observations of the Na I doublet that have proven particularly challenging to reproduce with current models of polarized line formation, even casting doubts on our very understanding of the physics of scattering polarization on the Sun. The experiment has confirmed the fundamental correctness of the current theory, and demonstrated that the "enigmatic'' polarization of those observations is exclusively of solar origin.

  18. Dark matter and dark energy interactions: theoretical challenges, cosmological implications and observational signatures.

    PubMed

    Wang, B; Abdalla, E; Atrio-Barandela, F; Pavón, D

    2016-09-01

    Models where dark matter and dark energy interact with each other have been proposed to solve the coincidence problem. We review the motivations underlying the need to introduce such interaction, its influence on the background dynamics and how it modifies the evolution of linear perturbations. We test models using the most recent observational data and we find that the interaction is compatible with the current astronomical and cosmological data. Finally, we describe the forthcoming data sets from current and future facilities that are being constructed or designed that will allow a clearer understanding of the physics of the dark sector.

  19. Managing community acquired pneumonia in the elderly - the next generation of pharmacotherapy on the horizon.

    PubMed

    Amalakuhan, B; Echevarria, K L; Restrepo, M I

    2017-08-01

    Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns. Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the 'San Antonio NIPS model', we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly. Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician's focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.

  20. Theoretical Approaches in Evolutionary Ecology: Environmental Feedback as a Unifying Perspective.

    PubMed

    Lion, Sébastien

    2018-01-01

    Evolutionary biology and ecology have a strong theoretical underpinning, and this has fostered a variety of modeling approaches. A major challenge of this theoretical work has been to unravel the tangled feedback loop between ecology and evolution. This has prompted the development of two main classes of models. While quantitative genetics models jointly consider the ecological and evolutionary dynamics of a focal population, a separation of timescales between ecology and evolution is assumed by evolutionary game theory, adaptive dynamics, and inclusive fitness theory. As a result, theoretical evolutionary ecology tends to be divided among different schools of thought, with different toolboxes and motivations. My aim in this synthesis is to highlight the connections between these different approaches and clarify the current state of theory in evolutionary ecology. Central to this approach is to make explicit the dependence on environmental dynamics of the population and evolutionary dynamics, thereby materializing the eco-evolutionary feedback loop. This perspective sheds light on the interplay between environmental feedback and the timescales of ecological and evolutionary processes. I conclude by discussing some potential extensions and challenges to our current theoretical understanding of eco-evolutionary dynamics.

  1. EIT forward problem parallel simulation environment with anisotropic tissue and realistic electrode models.

    PubMed

    De Marco, Tommaso; Ries, Florian; Guermandi, Marco; Guerrieri, Roberto

    2012-05-01

    Electrical impedance tomography (EIT) is an imaging technology based on impedance measurements. To retrieve meaningful insights from these measurements, EIT relies on detailed knowledge of the underlying electrical properties of the body. This is obtained from numerical models of current flows therein. The nonhomogeneous and anisotropic electric properties of human tissues make accurate modeling and simulation very challenging, leading to a tradeoff between physical accuracy and technical feasibility, which at present severely limits the capabilities of EIT. This work presents a complete algorithmic flow for an accurate EIT modeling environment featuring high anatomical fidelity with a spatial resolution equal to that provided by an MRI and a novel realistic complete electrode model implementation. At the same time, we demonstrate that current graphics processing unit (GPU)-based platforms provide enough computational power that a domain discretized with five million voxels can be numerically modeled in about 30 s.

  2. Recent Progresses in Incorporating Human Land-Water Management into Global Land Surface Models Toward Their Integration into Earth System Models

    NASA Technical Reports Server (NTRS)

    Pokhrel, Yadu N.; Hanasaki, Naota; Wada, Yoshihide; Kim, Hyungjun

    2016-01-01

    The global water cycle has been profoundly affected by human land-water management. As the changes in the water cycle on land can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to represent human land-water management in Earth system models (ESMs). During the recent past, noteworthy progress has been made in large-scale modeling of human impacts on the water cycle but sufficient advancements have not yet been made in integrating the newly developed schemes into ESMs. This study reviews the progresses made in incorporating human factors in large-scale hydrological models and their integration into ESMs. The study focuses primarily on the recent advancements and existing challenges in incorporating human impacts in global land surface models (LSMs) as a way forward to the development of ESMs with humans as integral components, but a brief review of global hydrological models (GHMs) is also provided. The study begins with the general overview of human impacts on the water cycle. Then, the algorithms currently employed to represent irrigation, reservoir operation, and groundwater pumping are discussed. Next, methodological deficiencies in current modeling approaches and existing challenges are identified. Furthermore, light is shed on the sources of uncertainties associated with model parameterizations, grid resolution, and datasets used for forcing and validation. Finally, representing human land-water management in LSMs is highlighted as an important research direction toward developing integrated models using ESM frameworks for the holistic study of human-water interactions within the Earths system.

  3. Improving Atrial Fibrillation Therapy: Is There a Gene for That?

    PubMed Central

    Hucker, William J.; Hanley, Alan; Ellinor, Patrick T.

    2017-01-01

    Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment. In this review, we will summarize the available published data on gene therapy and discuss the challenges, opportunities, and limitations of this approach. PMID:28427583

  4. Ranking of Business Process Simulation Software Tools with DEX/QQ Hierarchical Decision Model

    PubMed Central

    2016-01-01

    The omnipresent need for optimisation requires constant improvements of companies’ business processes (BPs). Minimising the risk of inappropriate BP being implemented is usually performed by simulating the newly developed BP under various initial conditions and “what-if” scenarios. An effectual business process simulations software (BPSS) is a prerequisite for accurate analysis of an BP. Characterisation of an BPSS tool is a challenging task due to the complex selection criteria that includes quality of visual aspects, simulation capabilities, statistical facilities, quality reporting etc. Under such circumstances, making an optimal decision is challenging. Therefore, various decision support models are employed aiding the BPSS tool selection. The currently established decision support models are either proprietary or comprise only a limited subset of criteria, which affects their accuracy. Addressing this issue, this paper proposes a new hierarchical decision support model for ranking of BPSS based on their technical characteristics by employing DEX and qualitative to quantitative (QQ) methodology. Consequently, the decision expert feeds the required information in a systematic and user friendly manner. There are three significant contributions of the proposed approach. Firstly, the proposed hierarchical model is easily extendible for adding new criteria in the hierarchical structure. Secondly, a fully operational decision support system (DSS) tool that implements the proposed hierarchical model is presented. Finally, the effectiveness of the proposed hierarchical model is assessed by comparing the resulting rankings of BPSS with respect to currently available results. PMID:26871694

  5. Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer.

    PubMed

    Zloza, Andrew; Karolina Palucka, A; Coussens, Lisa M; Gotwals, Philip J; Headley, Mark B; Jaffee, Elizabeth M; Lund, Amanda W; Sharpe, Arlene H; Sznol, Mario; Wainwright, Derek A; Wong, Kwok-Kin; Bosenberg, Marcus W

    2017-09-19

    Understanding how murine models can elucidate the mechanisms underlying antitumor immune responses and advance immune-based drug development is essential to advancing the field of cancer immunotherapy. The Society for Immunotherapy of Cancer (SITC) convened a workshop titled, "Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy" as part of the SITC 31st Annual Meeting and Associated Programs on November 10, 2016 in National Harbor, MD. The workshop focused on key issues in optimizing models for cancer immunotherapy research, with discussions on the strengths and weaknesses of current models, approaches to improve the predictive value of mouse models, and advances in cancer modeling that are anticipated in the near future. This full-day program provided an introduction to the most common immunocompetent and humanized models used in cancer immunology and immunotherapy research, and addressed the use of models to evaluate immune-targeting therapies. Here, we summarize the workshop presentations and subsequent panel discussion.

  6. Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.

    PubMed

    Rollin, Michael D H; Rollin, Bernard E

    2014-04-01

    Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.

  7. Systems metabolic engineering of microorganisms to achieve large-scale production of flavonoid scaffolds.

    PubMed

    Wu, Junjun; Du, Guocheng; Zhou, Jingwen; Chen, Jian

    2014-10-20

    Flavonoids possess pharmaceutical potential due to their health-promoting activities. The complex structures of these products make extraction from plants difficult, and chemical synthesis is limited because of the use of many toxic solvents. Microbial production offers an alternate way to produce these compounds on an industrial scale in a more economical and environment-friendly manner. However, at present microbial production has been achieved only on a laboratory scale and improvements and scale-up of these processes remain challenging. Naringenin and pinocembrin, which are flavonoid scaffolds and precursors for most of the flavonoids, are the model molecules that are key to solving the current issues restricting industrial production of these chemicals. The emergence of systems metabolic engineering, which combines systems biology with synthetic biology and evolutionary engineering at the systems level, offers new perspectives on strain and process optimization. In this review, current challenges in large-scale fermentation processes involving flavonoid scaffolds and the strategies and tools of systems metabolic engineering used to overcome these challenges are summarized. This will offer insights into overcoming the limitations and challenges of large-scale microbial production of these important pharmaceutical compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description.

    PubMed

    Spyrakis, Francesca; Cavasotto, Claudio N

    2015-10-01

    Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Outcome of a Workshop on Applications of Protein Models in Biomedical Research

    PubMed Central

    Schwede, Torsten; Sali, Andrej; Honig, Barry; Levitt, Michael; Berman, Helen M.; Jones, David; Brenner, Steven E.; Burley, Stephen K.; Das, Rhiju; Dokholyan, Nikolay V.; Dunbrack, Roland L.; Fidelis, Krzysztof; Fiser, Andras; Godzik, Adam; Huang, Yuanpeng Janet; Humblet, Christine; Jacobson, Matthew P.; Joachimiak, Andrzej; Krystek, Stanley R.; Kortemme, Tanja; Kryshtafovych, Andriy; Montelione, Gaetano T.; Moult, John; Murray, Diana; Sanchez, Roberto; Sosnick, Tobin R.; Standley, Daron M.; Stouch, Terry; Vajda, Sandor; Vasquez, Max; Westbrook, John D.; Wilson, Ian A.

    2009-01-01

    Summary We describe the proceedings and conclusions from a “Workshop on Applications of Protein Models in Biomedical Research” that was held at University of California at San Francisco on 11 and 12 July, 2008. At the workshop, international scientists involved with structure modeling explored (i) how models are currently used in biomedical research, (ii) what the requirements and challenges for different applications are, and (iii) how the interaction between the computational and experimental research communities could be strengthened to advance the field. PMID:19217386

  10. Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing

    PubMed Central

    Yan, Qiang; Fong, Stephen S.

    2017-01-01

    Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1) current techniques in controlling gene expression (transcriptional/translational level), (2) advances in site-specific genome engineering tools [homologous recombination (HR) and clustered regularly interspaced short palindromic repeats (CRISPR)], and (3) advances in genome-scale metabolic models (GSMMs) in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP) will be discussed along with some brief comments on foreseeable future prospects. PMID:29123506

  11. Future Supply Chains Enabled by Continuous Processing—Opportunities and Challenges. May 20–21, 2014 Continuous Manufacturing Symposium

    PubMed Central

    Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

    2015-01-01

    This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily “continuous processing”-based supply chain. The current predominantly “large batch” and centralized manufacturing system designed for the “blockbuster” drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more “flow-through” operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The significant opportunities to moving to a supply chain flow-through operating model, with substantial opportunities in inventory reduction, lead-time to patient, and radically different product assurance/stability regimes. Scenarios for decentralized production models producing a greater variety of products with enhanced volume flexibility. Production, supply, and value chain footprints that are radically different from today's monolithic and centralized batch manufacturing operations. Clinical trial and drug product development cost savings that support more rapid scale-up and market entry models with early involvement of SC designers within New Product Development. The major supply chain and industrial transformational challenges that need to be addressed. The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:840–849, 2015 PMID:25631279

  12. Which preparatory curriculum for the International Baccalaureate Diploma Programme is best? The challenge for international schools with regard to mathematics and science

    NASA Astrophysics Data System (ADS)

    Corlu, M. Sencer

    2014-12-01

    There are two mainstream curricula for international school students at the junior high level: the International Baccalaureate (IB) Middle Years Programme (MYP) and the Cambridge International General Certificate of Secondary Education (IGCSE). The former was developed in the mid-1990s and is currently being relaunched in a 21st-century approach. The latter programme of study was developed by University of Cambridge International Examinations in 1985 and has become popular in recent years among British domestic and international schools worldwide due to the clarity of its learning content. The prevailing uncertainty about which curriculum is best to prepare students for the IB Diploma Programme represents a challenge for international schools. The purpose of the current study is to develop a methodology through causal models which can explain the relationship between student performance in the IGCSE and the Diploma Programme with regard to mathematics and science. The data evaluated here consisted of external examination scores of students who attended a private international high school between the years 2005 and 2012. Two structural equation models were developed. The first model employed a maximum likelihood estimation, while the second model used a Bayesian estimation with a Markov Chain Monte Carlo method. Both models fit the data well. The evidence suggests that the IGCSE provides a good foundational preparation for the Diploma Programme in mathematics and science.

  13. Monte Carlo role in radiobiological modelling of radiotherapy outcomes

    NASA Astrophysics Data System (ADS)

    El Naqa, Issam; Pater, Piotr; Seuntjens, Jan

    2012-06-01

    Radiobiological models are essential components of modern radiotherapy. They are increasingly applied to optimize and evaluate the quality of different treatment planning modalities. They are frequently used in designing new radiotherapy clinical trials by estimating the expected therapeutic ratio of new protocols. In radiobiology, the therapeutic ratio is estimated from the expected gain in tumour control probability (TCP) to the risk of normal tissue complication probability (NTCP). However, estimates of TCP/NTCP are currently based on the deterministic and simplistic linear-quadratic formalism with limited prediction power when applied prospectively. Given the complex and stochastic nature of the physical, chemical and biological interactions associated with spatial and temporal radiation induced effects in living tissues, it is conjectured that methods based on Monte Carlo (MC) analysis may provide better estimates of TCP/NTCP for radiotherapy treatment planning and trial design. Indeed, over the past few decades, methods based on MC have demonstrated superior performance for accurate simulation of radiation transport, tumour growth and particle track structures; however, successful application of modelling radiobiological response and outcomes in radiotherapy is still hampered with several challenges. In this review, we provide an overview of some of the main techniques used in radiobiological modelling for radiotherapy, with focus on the MC role as a promising computational vehicle. We highlight the current challenges, issues and future potentials of the MC approach towards a comprehensive systems-based framework in radiobiological modelling for radiotherapy.

  14. Operationalizing the Space Weather Modeling Framework: Challenges and Resolutions

    NASA Astrophysics Data System (ADS)

    Welling, D. T.; Gombosi, T. I.; Toth, G.; Singer, H. J.; Millward, G. H.; Balch, C. C.; Cash, M. D.

    2016-12-01

    Predicting ground-based magnetic perturbations is a critical step towards specifying and predicting geomagnetically induced currents (GICs) in high voltage transmission lines. Currently, the Space Weather Modeling Framework (SWMF), a flexible modeling framework for simulating the multi-scale space environment, is being transitioned from research to operational use (R2O) by NOAA's Space Weather Prediction Center. Upon completion of this transition, the SWMF will provide localized time-varying magnetic field (dB/dt) predictions using real-time solar wind observations from L1 and the F10.7 proxy for EUV as model input. This presentation chronicles the challenges encountered during the R2O transition of the SWMF. Because operations relies on frequent calculations of global surface dB/dt, new optimizations were required to keep the model running faster than real time. Additionally, several singular situations arose during the 30-day robustness test that required immediate attention. Solutions and strategies for overcoming these issues will be presented. This includes new failsafe options for code execution, new physics and coupling parameters, and the development of an automated validation suite that allows us to monitor performance with code evolution. Finally, the operations-to-research (O2R) impact on SWMF-related research is presented. The lessons learned from this work are valuable and instructive for the space weather community as further R2O progress is made.

  15. Addressing the Big-Earth-Data Variety Challenge with the Hierarchical Triangular Mesh

    NASA Technical Reports Server (NTRS)

    Rilee, Michael L.; Kuo, Kwo-Sen; Clune, Thomas; Oloso, Amidu; Brown, Paul G.; Yu, Honfeng

    2016-01-01

    We have implemented an updated Hierarchical Triangular Mesh (HTM) as the basis for a unified data model and an indexing scheme for geoscience data to address the variety challenge of Big Earth Data. We observe that, in the absence of variety, the volume challenge of Big Data is relatively easily addressable with parallel processing. The more important challenge in achieving optimal value with a Big Data solution for Earth Science (ES) data analysis, however, is being able to achieve good scalability with variety. With HTM unifying at least the three popular data models, i.e. Grid, Swath, and Point, used by current ES data products, data preparation time for integrative analysis of diverse datasets can be drastically reduced and better variety scaling can be achieved. In addition, since HTM is also an indexing scheme, when it is used to index all ES datasets, data placement alignment (or co-location) on the shared nothing architecture, which most Big Data systems are based on, is guaranteed and better performance is ensured. Moreover, our updated HTM encoding turns most geospatial set operations into integer interval operations, gaining further performance advantages.

  16. Optimal input shaping for Fisher identifiability of control-oriented lithium-ion battery models

    NASA Astrophysics Data System (ADS)

    Rothenberger, Michael J.

    This dissertation examines the fundamental challenge of optimally shaping input trajectories to maximize parameter identifiability of control-oriented lithium-ion battery models. Identifiability is a property from information theory that determines the solvability of parameter estimation for mathematical models using input-output measurements. This dissertation creates a framework that exploits the Fisher information metric to quantify the level of battery parameter identifiability, optimizes this metric through input shaping, and facilitates faster and more accurate estimation. The popularity of lithium-ion batteries is growing significantly in the energy storage domain, especially for stationary and transportation applications. While these cells have excellent power and energy densities, they are plagued with safety and lifespan concerns. These concerns are often resolved in the industry through conservative current and voltage operating limits, which reduce the overall performance and still lack robustness in detecting catastrophic failure modes. New advances in automotive battery management systems mitigate these challenges through the incorporation of model-based control to increase performance, safety, and lifespan. To achieve these goals, model-based control requires accurate parameterization of the battery model. While many groups in the literature study a variety of methods to perform battery parameter estimation, a fundamental issue of poor parameter identifiability remains apparent for lithium-ion battery models. This fundamental challenge of battery identifiability is studied extensively in the literature, and some groups are even approaching the problem of improving the ability to estimate the model parameters. The first approach is to add additional sensors to the battery to gain more information that is used for estimation. The other main approach is to shape the input trajectories to increase the amount of information that can be gained from input-output measurements, and is the approach used in this dissertation. Research in the literature studies optimal current input shaping for high-order electrochemical battery models and focuses on offline laboratory cycling. While this body of research highlights improvements in identifiability through optimal input shaping, each optimal input is a function of nominal parameters, which creates a tautology. The parameter values must be known a priori to determine the optimal input for maximizing estimation speed and accuracy. The system identification literature presents multiple studies containing methods that avoid the challenges of this tautology, but these methods are absent from the battery parameter estimation domain. The gaps in the above literature are addressed in this dissertation through the following five novel and unique contributions. First, this dissertation optimizes the parameter identifiability of a thermal battery model, which Sergio Mendoza experimentally validates through a close collaboration with this dissertation's author. Second, this dissertation extends input-shaping optimization to a linear and nonlinear equivalent-circuit battery model and illustrates the substantial improvements in Fisher identifiability for a periodic optimal signal when compared against automotive benchmark cycles. Third, this dissertation presents an experimental validation study of the simulation work in the previous contribution. The estimation study shows that the automotive benchmark cycles either converge slower than the optimized cycle, or not at all for certain parameters. Fourth, this dissertation examines how automotive battery packs with additional power electronic components that dynamically route current to individual cells/modules can be used for parameter identifiability optimization. While the user and vehicle supervisory controller dictate the current demand for these packs, the optimized internal allocation of current still improves identifiability. Finally, this dissertation presents a robust Bayesian sequential input shaping optimization study to maximize the conditional Fisher information of the battery model parameters without prior knowledge of the nominal parameter set. This iterative algorithm only requires knowledge of the prior parameter distributions to converge to the optimal input trajectory.

  17. EPOS: Integrating seismological Research Infrastructures within Europe

    NASA Astrophysics Data System (ADS)

    Eck Van, Torild; Clinton, John; Haslinger, Florian; Michelini, Alberto

    2013-04-01

    Seismological data, products and models are currently produced in Europe within individual countries or research organizations, and with the contribution of coordinating organizations like ORFEUS and EMSC. In spite of these partly scattered resources, significant scientific results are obtained, excellent monitoring and information systems are operational and a huge amount of research quality data is being archived and disseminated. The seismological community, however, realizes that an effective European-scale integration of seismological and related geophysical data, products and models, combined with broad and easy access, is needed to facilitate future top level geoscience, for example, to appropriately harness the technological advancements enabling large scale and near-real time data processing. Here we present the technical concepts and developments within European seismology that will build the next generation of integrated services. Within the EPOS initiative and a number of related projects, where seismology infrastructure and IT developments are merging, in depth discussions are on-going on how to realize an effective integration. Concepts and visions addressing the obviously complex challenges resulting from the current highly distributed facilities and resources in Europe are emerging and are already partly being implemented. We will provide an overview of developments within key EU projects (NERA, VERCE, COOPEUS, EUDAT, REAKT, COMMIT, etc) and demonstrate how these are in coherence with EPOS and other on-going global initiatives. Within seismology current focus is on addressing IT related challenges to a) organize distributed data archives, develop metadata attributes for improved data searching, specifically including quality indicators, and define products from data and/or models, and b) define and create(on-line) monitoring, data access and processing tools. While developments to meet those challenges originate partly from within the community itself, it is important to harvest relevant ideas and tools from other scientific communities dealing with similar issues. We will present a short summary of those developments and how they fit within the proposed visions and concepts. These integration developments address a wide framework of seismological services that include: basic seismological data services (waveform data from velocity and acceleration sensors from land and underwater sites); seismological data products (source mechanism and process estimates, earthquake catalogues, structural and tomography model estimations); seismological models (synthetic waveforms, earth and earthquake source models, hazard models).Our aim is to build significantlyimproved seismological services and valuable products for multidisciplinary earth science research.

  18. The lingering presence of the Nightingale legacy.

    PubMed

    Hegge, Margaret J

    2011-04-01

    The history of the nursing profession is still evolving. One-hundred years ago, Nightingale died, leaving a legacy of philosophical cornerstones that still infuses the profession. Her idealism flows through her writings, as fresh today as 150 years ago. The initiatives of nursing today had their roots in Nightingale ideals. The alignment of current trends in nursing with Nightingale constructs is striking. Contemporary nurses are challenged to propel these ideals forward. The author here tracks Nightingale quotes, events, and writings with current initiatives, linking philosophical ideals to practical realities of current nursing practice. Nightingale constructs influencing nursing theories and models are examined.

  19. Modelling the impacts of pests and diseases on agricultural systems.

    PubMed

    Donatelli, M; Magarey, R D; Bregaglio, S; Willocquet, L; Whish, J P M; Savary, S

    2017-07-01

    The improvement and application of pest and disease models to analyse and predict yield losses including those due to climate change is still a challenge for the scientific community. Applied modelling of crop diseases and pests has mostly targeted the development of support capabilities to schedule scouting or pesticide applications. There is a need for research to both broaden the scope and evaluate the capabilities of pest and disease models. Key research questions not only involve the assessment of the potential effects of climate change on known pathosystems, but also on new pathogens which could alter the (still incompletely documented) impacts of pests and diseases on agricultural systems. Yield loss data collected in various current environments may no longer represent a adequate reference to develop tactical, decision-oriented, models for plant diseases and pests and their impacts, because of the ongoing changes in climate patterns. Process-based agricultural simulation modelling, on the other hand, appears to represent a viable methodology to estimate the impacts of these potential effects. A new generation of tools based on state-of-the-art knowledge and technologies is needed to allow systems analysis including key processes and their dynamics over appropriate suitable range of environmental variables. This paper offers a brief overview of the current state of development in coupling pest and disease models to crop models, and discusses technical and scientific challenges. We propose a five-stage roadmap to improve the simulation of the impacts caused by plant diseases and pests; i) improve the quality and availability of data for model inputs; ii) improve the quality and availability of data for model evaluation; iii) improve the integration with crop models; iv) improve the processes for model evaluation; and v) develop a community of plant pest and disease modelers.

  20. Laboratory test of a novel structural model of anxiety sensitivity and panic vulnerability.

    PubMed

    Bernstein, Amit; Zvolensky, Michael J; Zvolensky, Michael J; Schmidt, Norman B

    2009-06-01

    The current study evaluated a novel latent structural model of anxiety sensitivity (AS) in relation to panic vulnerability among a sample of young adults (N=216). AS was measured using the 16-item Anxiety Sensitivity Index (ASI; Reiss, Peterson, Gursky, & McNally, 1986), and panic vulnerability was indexed by panic attack responding to a single administration of a 4-minute, 10% CO(2) challenge. As predicted, vulnerability for panic attack responding to biological challenge was associated with dichotomous individual differences between taxonic AS classes and continuous within-taxon class individual differences in AS physical concerns. Findings supported the AS taxonic-dimensional hypothesis of AS latent structure and panic vulnerability. These findings are discussed in terms of their theoretical and clinical implications.

  1. An oral exam model for teaching advanced "Batchelor-level" fluid mechanics in the US

    NASA Astrophysics Data System (ADS)

    Freund, Jonathan

    2016-11-01

    A teaching model is developed to meet the challenge of teaching fluid mechanics at what might be considered a high level, at least by the current norms in the US. The initial goal was to avoid loss of concepts amidst the challenge of particular mathematical manipulations on particular assignments. However, it evolved toward fostering facile working knowledge of challenging material, such as in the books by Batchelor (e.g. streaming flow), Whitham (e.g. ship waves), and van Dyke (e.g. second-order boundary layer). To this end, the course model forgoes traditional assigned problems to focus on completion, augmentation, and in-depth understanding of the lecture material. The lectures are relatively traditional in structure, albeit with somewhat more interactive examples. The main unusual feature-again, by modern US standards-was assessment via multiple half-hour oral exams. This model has now been successful over 8 semesters for 3 different graduate courses in 2 departments. For all, students were assume to have already completed a full course at a "Navier-Stokes level". The presentation will include specifics of the course and exam structure, impressions of positive outcomes from the instructor, and a summary of the overwhelmingly positive student feedback.

  2. Hydrological Modeling in Alaska with WRF-Hydro

    NASA Astrophysics Data System (ADS)

    Elmer, N. J.; Zavodsky, B.; Molthan, A.

    2017-12-01

    The operational National Water Model (NWM), implemented in August 2016, is an instantiation of the Weather Research and Forecasting hydrological extension package (WRF-Hydro). Currently, the NWM only covers the contiguous United States, but will be expanded to include an Alaska domain in the future. It is well known that Alaska presents several hydrological modeling challenges, including unique arctic/sub-arctic hydrological processes not observed elsewhere in the United States and a severe lack of in-situ observations for model initialization. This project sets up an experimental version of WRF-Hydro in Alaska mimicking the NWM to gauge the ability of WRF-Hydro to represent hydrological processes in Alaska and identify model calibration challenges. Recent and upcoming launches of hydrology-focused NASA satellite missions such as the Soil Moisture Active Passive (SMAP) and Surface Water Ocean Topography (SWOT) expand the spatial and temporal coverage of observations in Alaska, so this study also lays the groundwork for assimilating these NASA datasets into WRF-Hydro in the future.

  3. The Framework for 0-D Atmospheric Modeling (F0AM) v3.1

    NASA Technical Reports Server (NTRS)

    Wolfe, Glenn M.; Marvin, Margaret R.; Roberts, Sandra J.; Travis, Katherine R.; Liao, Jin

    2016-01-01

    The Framework for 0-D Atmospheric Modeling(F0AM) is a flexible and user-friendly MATLAB-based platform for simulation of atmospheric chemistry systems. The F0AM interface incorporates front-end configuration of observational constraints and model setups, making it readily adaptable to simulation of photochemical chambers, Lagrangian plumes, and steady-state or time-evolving solar cycles. Six different chemical mechanisms and three options for calculation of photolysis frequencies are currently available. Example simulations are presented to illustrate model capabilities and, more generally, highlight some of the advantages and challenges of 0-D box modeling.

  4. Shared decision making in senior medical students: results from a national survey.

    PubMed

    Zeballos-Palacios, Claudia; Quispe, Renato; Mongilardi, Nicole; Diaz-Arocutipa, Carlos; Mendez-Davalos, Carlos; Lizarraga, Natalia; Paz, Aldo; Montori, Victor M; Malaga, German

    2015-05-01

    To explore perceptions and experiences of Peruvian medical students about observed, preferred, and feasible decision-making approaches. We surveyed senior medical students from 19 teaching hospitals in 4 major cities in Peru. The self-administered questionnaire collected demographic information, current approach, exposure to role models for and training in shared decision making, and perceptions of the pertinence and feasibility of the different decision-making approaches in general as well as in challenging scenarios. A total of 327 senior medical students (51% female) were included. The mean age was 25 years. Among all respondents, 2% reported receiving both theoretical and practical training in shared decision making. While 46% of students identified their current decision-making approach as clinician-as-perfect-agent, 50% of students identified their teachers with the paternalistic approach. Remarkably, 53% of students thought shared decision making should be the preferred approach and 50% considered it feasible in Peru. Among the 10 challenging scenarios, shared decision making reached a plurality (40%) in only one scenario (terminally ill patients). Despite limited exposure and training, Peruvian medical students aspire to practice shared decision making but their current attitude reflects the less participatory approaches they see role modeled by their teachers. © The Author(s) 2015.

  5. Ecologic Niche Modeling and Spatial Patterns of Disease Transmission

    PubMed Central

    2006-01-01

    Ecologic niche modeling (ENM) is a growing field with many potential applications to questions regarding the geography and ecology of disease transmission. Specifically, ENM has the potential to inform investigations concerned with the geography, or potential geography, of vectors, hosts, pathogens, or human cases, and it can achieve fine spatial resolution without the loss of information inherent in many other techniques. Potential applications and current frontiers and challenges are reviewed. PMID:17326931

  6. Modeling microbial communities: current, developing, and future technologies for predicting microbial community interaction.

    PubMed

    Larsen, Peter; Hamada, Yuki; Gilbert, Jack

    2012-07-31

    Never has there been a greater opportunity for investigating microbial communities. Not only are the profound effects of microbial ecology on every aspect of Earth's geochemical cycles beginning to be understood, but also the analytical and computational tools for investigating microbial Earth are undergoing a rapid revolution. This environmental microbial interactome, the system of interactions between the microbiome and the environment, has shaped the planet's past and will undoubtedly continue to do so in the future. We review recent approaches for modeling microbial community structures and the interactions of microbial populations with their environments. Different modeling approaches consider the environmental microbial interactome from different aspects, and each provides insights to different facets of microbial ecology. We discuss the challenges and opportunities for the future of microbial modeling and describe recent advances in microbial community modeling that are extending current descriptive technologies into a predictive science. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Dendritic trafficking faces physiologically critical speed-precision tradeoffs

    DOE PAGES

    Williams, Alex H.; O'Donnell, Cian; Sejnowski, Terrence J.; ...

    2016-12-30

    Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’. Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimatesmore » of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. In conclusion, these findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.« less

  8. Dendritic trafficking faces physiologically critical speed-precision tradeoffs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Williams, Alex H.; O'Donnell, Cian; Sejnowski, Terrence J.

    Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’. Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimatesmore » of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. In conclusion, these findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.« less

  9. Levels of craving influence psychological challenge and physiological reactivity.

    PubMed

    Frings, Daniel; Eskisan, Guleser; Spada, Marcantonio M; Albery, Ian P

    2015-01-01

    Behavioural and cognitive pathways that lead to the activation and escalation of craving have been studied extensively. Conversely, limited efforts have been directed towards understanding how craving relates to motivational systems and neuroendocrine responses. These can be understood using the biopsychosocial model of challenge and threat. In the current study, forty participants with varying levels of chocolate craving undertook two word searches, with the prospect of winning a piece of chocolate. Amongst those with high levels of craving, participation in this task led to motivational states of challenge relative to those with lower levels. This was reflected by changes in cardiac reactivity driven by differences in sympathetic-adrenal-medullar and hypothalamic-pituitary-adrenal axis activation. This finding suggests that craving can be associated with states of motivational challenge and thus affect cardiac reactivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. A Generalized Framework for Modeling Next Generation 911 Implementations.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kelic, Andjelka; Aamir, Munaf Syed; Kelic, Andjelka

    This document summarizes the current state of Sandia 911 modeling capabilities and then addresses key aspects of Next Generation 911 (NG911) architectures for expansion of existing models. Analysis of three NG911 implementations was used to inform heuristics , associated key data requirements , and assumptions needed to capture NG911 architectures in the existing models . Modeling of NG911 necessitates careful consideration of its complexity and the diversity of implementations. Draft heuristics for constructing NG911 models are pres ented based on the analysis along with a summary of current challenges and ways to improve future NG911 modeling efforts . We foundmore » that NG911 relies on E nhanced 911 (E911) assets such as 911 selective routers to route calls originating from traditional tel ephony service which are a majority of 911 calls . We also found that the diversity and transitional nature of NG911 implementations necessitates significant and frequent data collection to ensure that adequate model s are available for crisis action support .« less

  11. Fractional Poisson-Nernst-Planck Model for Ion Channels I: Basic Formulations and Algorithms.

    PubMed

    Chen, Duan

    2017-11-01

    In this work, we propose a fractional Poisson-Nernst-Planck model to describe ion permeation in gated ion channels. Due to the intrinsic conformational changes, crowdedness in narrow channel pores, binding and trapping introduced by functioning units of channel proteins, ionic transport in the channel exhibits a power-law-like anomalous diffusion dynamics. We start from continuous-time random walk model for a single ion and use a long-tailed density distribution function for the particle jump waiting time, to derive the fractional Fokker-Planck equation. Then, it is generalized to the macroscopic fractional Poisson-Nernst-Planck model for ionic concentrations. Necessary computational algorithms are designed to implement numerical simulations for the proposed model, and the dynamics of gating current is investigated. Numerical simulations show that the fractional PNP model provides a more qualitatively reasonable match to the profile of gating currents from experimental observations. Meanwhile, the proposed model motivates new challenges in terms of mathematical modeling and computations.

  12. Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long-Standing Model.

    PubMed

    Leão, Anderson H F F; Sarmento-Silva, Aldair J; Santos, José R; Ribeiro, Alessandra M; Silva, Regina H

    2015-07-01

    The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L-DOPA and dopamine agonists. Nevertheless, with the introduction of toxin-induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD. © 2015 International Society of Neuropathology.

  13. INDIVIDUAL BASED MODELLING APPROACH TO THERMAL ...

    EPA Pesticide Factsheets

    Diadromous fish populations in the Pacific Northwest face challenges along their migratory routes from declining habitat quality, harvest, and barriers to longitudinal connectivity. Changes in river temperature regimes are producing an additional challenge for upstream migrating adult salmon and steelhead, species that are sensitive to absolute and cumulative thermal exposure. Adult salmon populations have been shown to utilize cold water patches along migration routes when mainstem river temperatures exceed thermal optimums. We are employing an individual based model (IBM) to explore the costs and benefits of spatially-distributed cold water refugia for adult migrating salmon. Our model, developed in the HexSim platform, is built around a mechanistic behavioral decision tree that drives individual interactions with their spatially explicit simulated environment. Population-scale responses to dynamic thermal regimes, coupled with other stressors such as disease and harvest, become emergent properties of the spatial IBM. Other model outputs include arrival times, species-specific survival rates, body energetic content, and reproductive fitness levels. Here, we discuss the challenges associated with parameterizing an individual based model of salmon and steelhead in a section of the Columbia River. Many rivers and streams in the Pacific Northwest are currently listed as impaired under the Clean Water Act as a result of high summer water temperatures. Adverse effec

  14. Phoenix's roadway closure and restriction system : lessons learned from the Metropolitan Model Deployment Initiative : providing enhanced traffic information to the public

    DOT National Transportation Integrated Search

    1998-01-01

    The purpose of the ITS Planning Handbook is to provide a tool to assist in meeting current challenges. Specifically, the purposes of the Handbook are to: (1) Identify and describe ways that ITS should be integrated with the mainstream transportation ...

  15. The Evolution of SCORM to Tin Can API: Implications for Instructional Design

    ERIC Educational Resources Information Center

    Lindert, Lisa; Su, Bude

    2016-01-01

    Integrating and documenting formal and informal learning experiences is challenging using the current Shareable Content Object Reference Model (SCORM) eLearning standard, which limits the media and data that are obtained from eLearning. In response to SCORM's limitations, corporate, military, and academic institutions have collaborated to develop…

  16. Virtual Laboratory for QoS Study in Next-Generation Networks with Metro Ethernet Access

    ERIC Educational Resources Information Center

    Gomez-Sacristan, Angel; Sempere-Paya, Victor M.; Rodriguez-Hernandez, Miguel A.

    2016-01-01

    Teaching in university engineering departments is currently facing a number of challenges, especially for those involved in the most innovative and dynamic areas of information and communication technology. Learning model developments that place greater weight on laboratory activities require investment in specific equipment that is often very…

  17. Social Influence on Information Technology Adoption and Sustained Use in Healthcare: A Hierarchical Bayesian Learning Method Analysis

    ERIC Educational Resources Information Center

    Hao, Haijing

    2013-01-01

    Information technology adoption and diffusion is currently a significant challenge in the healthcare delivery setting. This thesis includes three papers that explore social influence on information technology adoption and sustained use in the healthcare delivery environment using conventional regression models and novel hierarchical Bayesian…

  18. Tribology.

    PubMed

    Spencer, Nicholas D

    2012-01-01

    The 156th Faraday Discussion covered the field of tribology, focussing on the subtopics of biotribology, predictive modelling, smart surfaces, and future lubricated systems. The papers themselves covered topics that drew on the fields of biology, medicine, chemistry, physics, materials science and mechanical engineering, providing a challenging and fascinating insight into the current state of the field of tribology.

  19. Learning through a Foreign Language: Models, Methods and Outcomes.

    ERIC Educational Resources Information Center

    Masih, John, Ed.

    This book presents European perspectives on the means of structuring curricula that integrate content and language teaching, drawing on the experience of practitioners at a range of levels. It also provides details of the outcomes of such programs and describes the current and future challenges for wider scale adoption of content and language…

  20. Integrating the Multimedia Builder Software as an Educational Tool to Deliver Fairy Tales: Promoting Multiliteracies and Multimodality

    ERIC Educational Resources Information Center

    Eteokleous, Nikleia; Pavlou, Victoria; Tsolakidis, Simos

    2015-01-01

    As a way to respond to the contemporary challenges for promoting multiliteracies and multimodality in education, the current study proposes a theoretical framework--the multiliteracies model--in identifying, developing and evaluating multimodal material. The article examines, first theoretically and then empirically, the promotion of…

  1. Out on a Limb: The Efficacy of Teacher Induction in Secondary Schools

    ERIC Educational Resources Information Center

    Shockley, Robert; Watlington, Eliah; Felsher, Rivka

    2013-01-01

    This article reports the results of a qualitative meta-analysis study of the research and literature on the efficacy of teacher induction on the retention of high-quality secondary school teachers and challenges current assumptions about the efficacy of induction despite the proliferation of induction programs nationwide. A theoretical model for…

  2. Integrating Telemedicine for Disaster Response: Testing the Emergency Telemedicine Technology Acceptance Model

    ERIC Educational Resources Information Center

    Davis, Theresa M.

    2013-01-01

    Background: There is little evidence that technology acceptance is well understood in healthcare. The hospital environment is complex and dynamic creating a challenge when new technology is introduced because it impacts current processes and workflows which can significantly affect patient care delivery and outcomes. This study tested the effect…

  3. A Challenge for Social Studies Educators: Increasing Civility in Schools and Society by Modeling Civic Virtues

    ERIC Educational Resources Information Center

    Moore, James

    2012-01-01

    Many scholars, teachers, parents, as well as others, are concerned with the decline of civility in public discourse and public schools. The sharp differences among various ideological groups, exacerbated by media incivility, are contributing factors to rising incivility. This ideological divide currently manifests itself in bitter partisan…

  4. An Integrated Customer Knowledge Management Framework for Academic Libraries

    ERIC Educational Resources Information Center

    Daneshgar, Farhad; Parirokh, Mehri

    2012-01-01

    The ability of academic libraries to produce timely and effective responses to various environmental changes constitutes a major challenge for them to enhance their survival rate and maintain growth in competitive environments. This article provides a conceptual model as an analytical tool for both improving current services as well as creating…

  5. Inservice Education and the 6 O'Clock News. OSSC Bulletin Vol. 21, No. 7.

    ERIC Educational Resources Information Center

    Arends, Richard; And Others

    Several assumptions currently held by many inservice planners and deliverers are presented and challenged. A new model of inservice programs is outlined that pays attention to the characteristics of maturing and growing professional educators and that demands new forms for delivering inservice to individuals and school clients. Inservice delivery…

  6. Challenging the Knowledge-Transfer Orthodoxy: Knowledge Co-construction in Technology-Enhanced Learning for Children with Autism

    ERIC Educational Resources Information Center

    Guldberg, Karen; Parsons, Sarah; Porayska-Pomsta, Kaska; Keay-Bright, Wendy

    2017-01-01

    Experimental intervention studies constitute the current dominant research designs in the autism education field. Such designs are based on a "knowledge-transfer" model of evidence-based practice in which research is conducted by researchers, and is then "transferred" to practitioners to enable them to implement evidence-based…

  7. Learning from Japanese Approach to Teachers' Professional Development: Can "Jugyou Kenkyu" Work in Other Countries?

    ERIC Educational Resources Information Center

    Masami, Matoba; Reza, Sarkar Arani M.

    2005-01-01

    This paper tries to present a careful analysis of current trends and challenges to importing Japanese model of teachers' professional development. The objective is to examine what "we" can learn from Japanese approach to improving instruction, especially "Jugyou Kenkyu" (Lesson Study) as a collaborative research on the…

  8. Evaluating the Impact of Atmospheric Infrared Sounder (AIRS) Data On Convective Forecasts

    NASA Technical Reports Server (NTRS)

    Kozlowski, Danielle; Zavodsky, Bradley

    2011-01-01

    The Short-term Prediction Research and Transition Center (SPoRT) is a collaborative partnership between NASA and operational forecasting partners, including a number of National Weather Service (NWS) offices. SPoRT provides real-time NASA products and capabilities to its partners to address specific operational forecast challenges. The mission of SPoRT is to transition observations and research capabilities into operations to help improve short-term weather forecasts on a regional scale. Two areas of focus are data assimilation and modeling, which can to help accomplish SPoRT's programmatic goals of transitioning NASA data to operational users. Forecasting convective weather is one challenge that faces operational forecasters. Current numerical weather prediction (NWP) models that operational forecasters use struggle to properly forecast location, timing, intensity and/or mode of convection. Given the proper atmospheric conditions, convection can lead to severe weather. SPoRT's partners in the National Oceanic and Atmospheric Administration (NOAA) have a mission to protect the life and property of American citizens. This mission has been tested as recently as this 2011 severe weather season, which has seen more than 300 fatalities and injuries and total damages exceeding $10 billion. In fact, during the three day period from 25-27 April, 1,265 storms reports (362 tornado reports) were collected making this three day period one of most active in American history. To address the forecast challenge of convective weather, SPoRT produces a real-time NWP model called the SPoRT Weather Research and Forecasting (SPoRT-WRF), which incorporates unique NASA data sets. One of the NASA assets used in this unique model configuration is retrieved profiles from the Atmospheric Infrared Sounder (AIRS).The goal of this project is to determine the impact that these AIRS profiles have on the SPoRT-WRF forecasts by comparing to a current operational model and a control SPoRT-WRF model that does not contain AIRS profiles.

  9. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Progress and Preliminary Results

    NASA Astrophysics Data System (ADS)

    Rosenzweig, C.

    2011-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a distributed climate-scenario simulation exercise for historical model intercomparison and future climate change conditions with participation of multiple crop and agricultural trade modeling groups around the world. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Recent progress and the current status of AgMIP will be presented, highlighting three areas of activity: preliminary results from crop pilot studies, outcomes from regional workshops, and emerging scientific challenges. AgMIP crop modeling efforts are being led by pilot studies, which have been established for wheat, maize, rice, and sugarcane. These crop-specific initiatives have proven instrumental in testing and contributing to AgMIP protocols, as well as creating preliminary results for aggregation and input to agricultural trade models. Regional workshops are being held to encourage collaborations and set research activities in motion for key agricultural areas. The first of these workshops was hosted by Embrapa and UNICAMP and held in Campinas, Brazil. Outcomes from this meeting have informed crop modeling research activities within South America, AgMIP protocols, and future regional workshops. Several scientific challenges have emerged and are currently being addressed by AgMIP researchers. Areas of particular interest include geospatial weather generation, ensemble methods for climate scenarios and crop models, spatial aggregation of field-scale yields to regional and global production, and characterization of future changes in climate variability.

  10. A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses

    PubMed Central

    Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

    2015-01-01

    Background Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a “universal” LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Methodologies/principle findings Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Conclusions/significance Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever. PMID:25884628

  11. Polarization-induced Zener tunnel diodes in GaN/InGaN/GaN heterojunctions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yan, Xiaodong; Li, Wenjun; Islam, S. M.

    By the insertion of thin In{sub x}Ga{sub 1−x}N layers into Nitrogen-polar GaN p-n junctions, polarization-induced Zener tunnel junctions are studied. The reverse-bias interband Zener tunneling current is found to be weakly temperature dependent, as opposed to the strongly temperature-dependent forward bias current. This indicates tunneling as the primary reverse-bias current transport mechanism. The Indium composition in the InGaN layer is systematically varied to demonstrate the increase in the interband tunneling current. Comparing the experimentally measured tunneling currents to a model helps identify the specific challenges in potentially taking such junctions towards nitride-based polarization-induced tunneling field-effect transistors.

  12. The status and challenge of global fire modelling

    DOE PAGES

    Hantson, Stijn; Arneth, Almut; Harrison, Sandy P.; ...

    2016-06-09

    Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central questionmore » underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. In conclusion, we indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.« less

  13. The status and challenge of global fire modelling

    NASA Astrophysics Data System (ADS)

    Hantson, Stijn; Arneth, Almut; Harrison, Sandy P.; Kelley, Douglas I.; Prentice, I. Colin; Rabin, Sam S.; Archibald, Sally; Mouillot, Florent; Arnold, Steve R.; Artaxo, Paulo; Bachelet, Dominique; Ciais, Philippe; Forrest, Matthew; Friedlingstein, Pierre; Hickler, Thomas; Kaplan, Jed O.; Kloster, Silvia; Knorr, Wolfgang; Lasslop, Gitta; Li, Fang; Mangeon, Stephane; Melton, Joe R.; Meyn, Andrea; Sitch, Stephen; Spessa, Allan; van der Werf, Guido R.; Voulgarakis, Apostolos; Yue, Chao

    2016-06-01

    Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.

  14. The status and challenge of global fire modelling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hantson, Stijn; Arneth, Almut; Harrison, Sandy P.

    Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central questionmore » underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. In conclusion, we indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.« less

  15. Computational Challenges in the Analysis of Petrophysics Using Microtomography and Upscaling

    NASA Astrophysics Data System (ADS)

    Liu, J.; Pereira, G.; Freij-Ayoub, R.; Regenauer-Lieb, K.

    2014-12-01

    Microtomography provides detailed 3D internal structures of rocks in micro- to tens of nano-meter resolution and is quickly turning into a new technology for studying petrophysical properties of materials. An important step is the upscaling of these properties as micron or sub-micron resolution can only be done on the sample-scale of millimeters or even less than a millimeter. We present here a recently developed computational workflow for the analysis of microstructures including the upscaling of material properties. Computations of properties are first performed using conventional material science simulations at micro to nano-scale. The subsequent upscaling of these properties is done by a novel renormalization procedure based on percolation theory. We have tested the workflow using different rock samples, biological and food science materials. We have also applied the technique on high-resolution time-lapse synchrotron CT scans. In this contribution we focus on the computational challenges that arise from the big data problem of analyzing petrophysical properties and its subsequent upscaling. We discuss the following challenges: 1) Characterization of microtomography for extremely large data sets - our current capability. 2) Computational fluid dynamics simulations at pore-scale for permeability estimation - methods, computing cost and accuracy. 3) Solid mechanical computations at pore-scale for estimating elasto-plastic properties - computational stability, cost, and efficiency. 4) Extracting critical exponents from derivative models for scaling laws - models, finite element meshing, and accuracy. Significant progress in each of these challenges is necessary to transform microtomography from the current research problem into a robust computational big data tool for multi-scale scientific and engineering problems.

  16. Initial results from a dynamic coupled magnetosphere-ionosphere-ring current model

    NASA Astrophysics Data System (ADS)

    Pembroke, Asher; Toffoletto, Frank; Sazykin, Stanislav; Wiltberger, Michael; Lyon, John; Merkin, Viacheslav; Schmitt, Peter

    2012-02-01

    In this paper we describe a coupled model of Earth's magnetosphere that consists of the Lyon-Fedder-Mobarry (LFM) global magnetohydrodynamics (MHD) simulation, the MIX ionosphere solver and the Rice Convection Model (RCM) and report some results using idealized inputs and model parameters. The algorithmic and physical components of the model are described, including the transfer of magnetic field information and plasma boundary conditions to the RCM and the return of ring current plasma properties to the LFM. Crucial aspects of the coupling include the restriction of RCM to regions where field-line averaged plasma-β ≤ 1, the use of a plasmasphere model, and the MIX ionosphere model. Compared to stand-alone MHD, the coupled model produces a substantial increase in ring current pressure and reduction of the magnetic field near the Earth. In the ionosphere, stronger region-1 and region-2 Birkeland currents are seen in the coupled model but with no significant change in the cross polar cap potential drop, while the region-2 currents shielded the low-latitude convection potential. In addition, oscillations in the magnetic field are produced at geosynchronous orbit with the coupled code. The diagnostics of entropy and mass content indicate that these oscillations are associated with low-entropy flow channels moving in from the tail and may be related to bursty bulk flows and bubbles seen in observations. As with most complex numerical models, there is the ongoing challenge of untangling numerical artifacts and physics, and we find that while there is still much room for improvement, the results presented here are encouraging.

  17. Translational research in immune senescence: Assessing the relevance of current models

    PubMed Central

    High, Kevin P.; Akbar, Arne N.; Nikolich-Zugich, Janko

    2014-01-01

    Advancing age is accompanied by profound changes in immune function; some are induced by the loss of critical niches that support development of naïve cells (e.g. thymic involution), others by the intrinsic physiology of long-lived cells attempting to maintain homeostasis, still others by extrinsic effects such as oxidative stress or long-term exposure to antigen due to persistent viral infections. Once compensatory mechanisms can no longer maintain a youthful phenotype the end result is the immune senescent milieu – one characterized by chronic, low grade, systemic inflammation and impaired responses to immune challenge, particularly when encountering new antigens. This state is associated with progression of chronic illnesses like atherosclerosis and dementia, and an increased risk of acute illness, disability and death in older adults. The complex interaction between immune senescence and chronic illness provides an ideal landscape for translational research with the potential to greatly affect human health. However, current animal models and even human investigative strategies for immune senescence have marked limitations, and the reductionist paradigm itself may be poorly suited to meet these challenges. A new paradigm, one that embraces complexity as a core feature of research in older adults is required to address the critical health issues facing the burgeoning senior population, the group that consumes the majority of healthcare resources. In this review, we outline the major advantages and limitations of current models and offer suggestions for how to move forward. PMID:22633440

  18. An update on pharmaceutical film coating for drug delivery.

    PubMed

    Felton, Linda A; Porter, Stuart C

    2013-04-01

    Pharmaceutical coating processes have generally been transformed from what was essentially an art form in the mid-twentieth century to a much more technology-driven process. This review article provides a basic overview of current film coating processes, including a discussion on polymer selection, coating formulation additives and processing equipment. Substrate considerations for pharmaceutical coating processes are also presented. While polymeric coating operations are commonplace in the pharmaceutical industry, film coating processes are still not fully understood, which presents serious challenges with current regulatory requirements. Novel analytical technologies and various modeling techniques that are being used to better understand film coating processes are discussed. This review article also examines the challenges of implementing process analytical technologies in coating operations, active pharmaceutical ingredients in polymer film coatings, the use of high-solids coating systems and continuous coating and other novel coating application methods.

  19. Facial Animations: Future Research Directions & Challenges

    NASA Astrophysics Data System (ADS)

    Alkawaz, Mohammed Hazim; Mohamad, Dzulkifli; Rehman, Amjad; Basori, Ahmad Hoirul

    2014-06-01

    Nowadays, computer facial animation is used in a significant multitude fields that brought human and social to study the computer games, films and interactive multimedia reality growth. Authoring the computer facial animation, complex and subtle expressions are challenging and fraught with problems. As a result, the current most authored using universal computer animation techniques often limit the production quality and quantity of facial animation. With the supplement of computer power, facial appreciative, software sophistication and new face-centric methods emerging are immature in nature. Therefore, this paper concentrates to define and managerially categorize current and emerged surveyed facial animation experts to define the recent state of the field, observed bottlenecks and developing techniques. This paper further presents a real-time simulation model of human worry and howling with detail discussion about their astonish, sorrow, annoyance and panic perception.

  20. Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives.

    PubMed

    Ravnic, Dino J; Leberfinger, Ashley N; Koduru, Srinivas V; Hospodiuk, Monika; Moncal, Kazim K; Datta, Pallab; Dey, Madhuri; Rizk, Elias; Ozbolat, Ibrahim T

    2017-07-01

    : Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

  1. Review of 3D image data calibration for heterogeneity correction in proton therapy treatment planning.

    PubMed

    Zhu, Jiahua; Penfold, Scott N

    2016-06-01

    Correct modelling of the interaction parameters of patient tissues is of vital importance in proton therapy treatment planning because of the large dose gradients associated with the Bragg peak. Different 3D imaging techniques yield different information regarding these interaction parameters. Given the rapidly expanding interest in proton therapy, this review is written to make readers aware of the current challenges in accounting for tissue heterogeneities and the imaging systems that are proposed to tackle these challenges. A summary of the interaction parameters of interest in proton therapy and the current and developmental 3D imaging techniques used in proton therapy treatment planning is given. The different methods to translate the imaging data to the interaction parameters of interest are reviewed and a summary of the implementations in several commercial treatment planning systems is presented.

  2. Mathematical Models of Blast-Induced TBI: Current Status, Challenges, and Prospects

    PubMed Central

    Gupta, Raj K.; Przekwas, Andrzej

    2013-01-01

    Blast-induced traumatic brain injury (TBI) has become a signature wound of recent military activities and is the leading cause of death and long-term disability among U.S. soldiers. The current limited understanding of brain injury mechanisms impedes the development of protection, diagnostic, and treatment strategies. We believe mathematical models of blast wave brain injury biomechanics and neurobiology, complemented with in vitro and in vivo experimental studies, will enable a better understanding of injury mechanisms and accelerate the development of both protective and treatment strategies. The goal of this paper is to review the current state of the art in mathematical and computational modeling of blast-induced TBI, identify research gaps, and recommend future developments. A brief overview of blast wave physics, injury biomechanics, and the neurobiology of brain injury is used as a foundation for a more detailed discussion of multiscale mathematical models of primary biomechanics and secondary injury and repair mechanisms. The paper also presents a discussion of model development strategies, experimental approaches to generate benchmark data for model validation, and potential applications of the model for prevention and protection against blast wave TBI. PMID:23755039

  3. A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model

    PubMed Central

    Fullen, Daniel J.; Murray, Bryan; Mori, Julie; Catchpole, Andrew; Borley, Daryl W.; Murray, Edward J.; Balaratnam, Ganesh; Gilbert, Anthony; Mann, Alex; Hughes, Fiona; Lambkin-Williams, Rob

    2016-01-01

    Background Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. Methods and Stock Development A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children’s Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. Human Challenge and Conclusions In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. Trial Registration ClinicalTrials.gov NCT02522832 PMID:27936016

  4. Prediction of Metabolism of Drugs using Artificial Intelligence: How far have we reached?

    PubMed

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2016-01-01

    Information about drug metabolism is an essential component of drug development. Modeling the drug metabolism requires identification of the involved enzymes, rate and extent of metabolism, the sites of metabolism etc. There has been continuous attempts in the prediction of metabolism of drugs using artificial intelligence in effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are number of predictive models available for metabolism using Support vector machines, Artificial neural networks, Bayesian classifiers etc. There is an urgent need to review their progress so far and address the existing challenges in prediction of metabolism. In this attempt, we are presenting the currently available literature models and some of the critical issues regarding prediction of drug metabolism.

  5. The Split-Brain Phenomenon Revisited: A Single Conscious Agent with Split Perception.

    PubMed

    Pinto, Yair; de Haan, Edward H F; Lamme, Victor A F

    2017-11-01

    The split-brain phenomenon is caused by the surgical severing of the corpus callosum, the main route of communication between the cerebral hemispheres. The classical view of this syndrome asserts that conscious unity is abolished. The left hemisphere consciously experiences and functions independently of the right hemisphere. This view is a cornerstone of current consciousness research. In this review, we first discuss the evidence for the classical view. We then propose an alternative, the 'conscious unity, split perception' model. This model asserts that a split brain produces one conscious agent who experiences two parallel, unintegrated streams of information. In addition to changing our view of the split-brain phenomenon, this new model also poses a serious challenge for current dominant theories of consciousness. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Method meets application: on the use of earthquake scenarios in community-based disaster preparedness and response

    NASA Astrophysics Data System (ADS)

    Sargeant, S.; Sorensen, M. B.

    2011-12-01

    More than 50% of the world's population now live in urban areas. In less developed countries, future urban population increase will be due to natural population growth and rural-to-urban migration. As urban growth continues, the vulnerability of those living in these areas is also increasing. This presents a wide variety of challenges for humanitarian organisations that often have more experience of disaster response in rural settings rather than planning for large urban disasters. The 2010 Haiti earthquake highlighted the vulnerability of these organisations and the communities that they seek to support. To meet this challenge, a key consideration is how scientific information can support the humanitarian sector and their working practices. Here we review the current state of earthquake scenario modelling practice, with special focus on scenarios to be used in disaster response and response planning, and present an evaluation of how the field looks set to evolve. We also review current good practice and lessons learned from previous earthquakes with respect to planning for and responding to earthquakes in urban settings in the humanitarian sector, identifying key sectoral priorities. We then investigate the interface between these two areas to investigate the use of earthquake scenarios in disaster response planning and identify potential challenges both with respect to development of scientific models and their application on the ground.

  7. Improving Atrial Fibrillation Therapy: Is There a Gene for That?

    PubMed

    Hucker, William J; Hanley, Alan; Ellinor, Patrick T

    2017-04-25

    Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment. In this review, we summarize the available published data on gene therapy and discuss the challenges, opportunities, and limitations of this approach. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Modeling of Dual Gate Material Hetero-dielectric Strained PNPN TFET for Improved ON Current

    NASA Astrophysics Data System (ADS)

    Kumari, Tripty; Saha, Priyanka; Dash, Dinesh Kumar; Sarkar, Subir Kumar

    2018-01-01

    The tunnel field effect transistor (TFET) is considered to be a promising alternative device for future low-power VLSI circuits due to its steep subthreshold slope, low leakage current and its efficient performance at low supply voltage. However, the main challenging issue associated with realizing TFET for wide scale applications is its low ON current. To overcome this, a dual gate material with the concept of dielectric engineering has been incorporated into conventional TFET structure to tune the tunneling width at source-channel interface allowing significant flow of carriers. In addition to this, N+ pocket is implanted at source-channel junction of the proposed structure and the effect of strain is added for exploring the performance of the model in nanoscale regime. All these added features upgrade the device characteristics leading to higher ON current, low leakage and low threshold voltage. The present work derives the surface potential, electric field expression and drain current by solving 2D Poisson's equation at different boundary conditions. A comparative analysis of proposed model with conventional TFET has been done to establish the superiority of the proposed structure. All analytical results have been compared with the results obtained in SILVACO ATLAS device simulator to establish the accuracy of the derived analytical model.

  9. Model-Based Systems Engineering Approach to Managing Mass Margin

    NASA Technical Reports Server (NTRS)

    Chung, Seung H.; Bayer, Todd J.; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Christopher; Lam, Doris

    2012-01-01

    When designing a flight system from concept through implementation, one of the fundamental systems engineering tasks ismanaging the mass margin and a mass equipment list (MEL) of the flight system. While generating a MEL and computing a mass margin is conceptually a trivial task, maintaining consistent and correct MELs and mass margins can be challenging due to the current practices of maintaining duplicate information in various forms, such as diagrams and tables, and in various media, such as files and emails. We have overcome this challenge through a model-based systems engineering (MBSE) approach within which we allow only a single-source-of-truth. In this paper we describe the modeling patternsused to capture the single-source-of-truth and the views that have been developed for the Europa Habitability Mission (EHM) project, a mission concept study, at the Jet Propulsion Laboratory (JPL).

  10. Modeling Viral Spread

    PubMed Central

    Graw, Frederik; Perelson, Alan S.

    2016-01-01

    The way in which a viral infection spreads within a host is a complex process that is not well understood. Different viruses, such as human immunodeficiency virus type 1 and hepatitis C virus, have evolved different strategies, including direct cell-to-cell transmission and cell-free transmission, to spread within a host. To what extent these two modes of transmission are exploited in vivo is still unknown. Mathematical modeling has been an essential tool to get a better systematic and quantitative understanding of viral processes that are difficult to discern through strictly experimental approaches. In this review, we discuss recent attempts that combine experimental data and mathematical modeling in order to determine and quantify viral transmission modes. We also discuss the current challenges for a systems-level understanding of viral spread, and we highlight the promises and challenges that novel experimental techniques and data will bring to the field. PMID:27618637

  11. Advances in modelling of condensation phenomena

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, W.S.; Zaltsgendler, E.; Hanna, B.

    1997-07-01

    The physical parameters in the modelling of condensation phenomena in the CANDU reactor system codes are discussed. The experimental programs used for thermal-hydraulic code validation in the Canadian nuclear industry are briefly described. The modelling of vapour generation and in particular condensation plays a key role in modelling of postulated reactor transients. The condensation models adopted in the current state-of-the-art two-fluid CANDU reactor thermal-hydraulic system codes (CATHENA and TUF) are described. As examples of the modelling challenges faced, the simulation of a cold water injection experiment by CATHENA and the simulation of a condensation induced water hammer experiment by TUFmore » are described.« less

  12. Quantifying the probability of record-setting heat events in the historical record and at different levels of climate forcing

    NASA Astrophysics Data System (ADS)

    Diffenbaugh, N. S.

    2017-12-01

    Severe heat provides one of the most direct, acute, and rapidly changing impacts of climate on people and ecostystems. Theory, historical observations, and climate model simulations all suggest that global warming should increase the probability of hot events that fall outside of our historical experience. Given the acutre impacts of extreme heat, quantifying the probability of historically unprecedented hot events at different levels of climate forcing is critical for climate adaptation and mitigation decisions. However, in practice that quantification presents a number of methodological challenges. This presentation will review those methodological challenges, including the limitations of the observational record and of climate model fidelity. The presentation will detail a comprehensive approach to addressing these challenges. It will then demonstrate the application of that approach to quantifying uncertainty in the probability of record-setting hot events in the current climate, as well as periods with lower and higher greenhouse gas concentrations than the present.

  13. Brain Metastasis: Unique Challenges and Open Opportunities

    PubMed Central

    Lowery, Frank J.; Yu, Dihua

    2016-01-01

    The metastasis of cancer to the central nervous system (CNS) remains a devastating clinical reality, carrying an estimated survival time of less than one year in spite of recent therapeutic breakthroughs for other disease contexts. Advances in brain metastasis research are hindered by a number of reasons, including its complicated nature and the difficulty of modeling metastatic cancer growth in the unique brain microenvironment. In this review, we will discuss the clinical challenge, and compare the values and limitations of the available models for brain metastasis research. Additionally, we will specifically address current knowledge on how brain metastases take advantage of the unique brain environment to benefit their own growth. Finally, we will explore the distinctive metabolic and nutrient characteristics of the brain; how these paradoxically represent barriers to establishment of brain metastasis, but also provide ample supplies for metastatic cells’ growth in the brain. We envision that multi-disciplinary innovative approaches will open opportunities for the field to make breakthroughs in tackling unique challenges of brain metastasis. PMID:27939792

  14. Professional self-efficacy as a predictor of burnout and engagement: the role of challenge and hindrance demands.

    PubMed

    Ventura, Mercedes; Salanova, Marisa; Llorens, Susana

    2015-01-01

    The objective of the current study is to analyze the role of professional self-efficacy as a predictor of psychosocial well-being (i.e., burnout and engagement) following the Social Cognitive Theory of Albert Bandura (1997). Structural Equation Modeling was performed in a sample of secondary school teachers (n = 460) and users of Information and Communication Technology (n = 596). Results show empirical support for the predicting role that professional self-efficacy plays in the perception of challenge (i.e., mental overload) and hindrance demands (i.e., role conflict, lack of control, and lack of social support), which are in turn related to burnout (i.e., erosion process) and engagement (i.e., motivational process). Specifically, employees with more professional self-efficacy will perceive more challenge demands and fewer hindrance demands, and this will in turn relate to more engagement and less burnout. A multi-group analysis showed that the research model was invariant across both samples. Theoretical and practical implications are discussed.

  15. Additive Manufacturing (AM) in Expeditionary Operations: Current Needs, Technical Challenges, and Opportunities

    DTIC Science & Technology

    2016-06-01

    site customization of existing models. The author performed an empirical study centered around a survey of United States Marine Corps (USMC) and United...recommends that more studies be performed to determine the best way forward for AM within the USMC and USN. 14. SUBJECT TERMS 3D printing, additive...customization of existing models. The author performed an em- pirical study centered around a survey of United States Marine Corps (USMC) and United

  16. Hardware-in-the-Loop Power Extraction Using Different Real-Time Platforms (PREPRINT)

    DTIC Science & Technology

    2008-07-01

    engine controller ( FADEC ). Incorporating various transient subsystem level models into a complex modeling tool can be a challenging process when each...used can also be modified or replaced as appropriate. In its current configuration, the generic turbine engine model’s FADEC runs primarily on a...simulation in real-time, two platforms were tested: dSPACE and National Instruments’ (NI) LabVIEW Real-Time. For both dSPACE and NI, the engine and FADEC

  17. Preclinical evaluation of bacterially produced RSV-G protein vaccine: Strong protection against RSV challenge in cotton rat model.

    PubMed

    Fuentes, Sandra; Klenow, Laura; Golding, Hana; Khurana, Surender

    2017-02-10

    In current study, we evaluated the safety and protective efficacy of recombinant unglycosylated RSV G protein ectodomain produced in E. coli (in presence and absence of oil-in-water adjuvant) in a preclinical RSV susceptible cotton rat challenge model compared to formaldehyde inactivated RSV (FI-RSV) and live RSV experimental infection. The adjuvanted G protein vaccine induced robust neutralization antibody responses comparable to those generated by live RSV infection. Importantly, adjuvanted G protein significantly reduced viral loads in both the lungs and nose at early time points following viral challenge. Antibody kinetics determined by Surface Plasmon Resonance showed that adjuvanted G generated 10-fold higher G-binding antibodies compared to non-adjvuanted G vaccine and live RSV infection, which correlated strongly with both neutralization titers and viral load titers in the nose and lungs post-viral challenge. Antibody diversity analysis revealed immunodominant antigenic sites in the N- and C-termini of the RSV-G protein, that were boosted >10-fold by adjuvant and inversely correlated with viral load titers. Enhanced lung pathology was observed only in animals vaccinated with FI-RSV, but not in animals vaccinated with unadjuvanted or adjuvanted RSV-G vaccine after viral challenge. The bacterially produced unglycosylated G protein could be developed as a protective vaccine against RSV disease.

  18. Impact analysis of air gap motion with respect to parameters of mooring system for floating platform

    NASA Astrophysics Data System (ADS)

    Shen, Zhong-xiang; Huo, Fa-li; Nie, Yan; Liu, Yin-dong

    2017-04-01

    In this paper, the impact analysis of air gap concerning the parameters of mooring system for the semi-submersible platform is conducted. It is challenging to simulate the wave, current and wind loads of a platform based on a model test simultaneously. Furthermore, the dynamic equivalence between the truncated and full-depth mooring system is still a tuff work. However, the wind and current loads can be tested accurately in wind tunnel model. Furthermore, the wave can be simulated accurately in wave tank test. The full-scale mooring system and the all environment loads can be simulated accurately by using the numerical model based on the model tests simultaneously. In this paper, the air gap response of a floating platform is calculated based on the results of tunnel test and wave tank. Meanwhile, full-scale mooring system, the wind, wave and current load can be considered simultaneously. In addition, a numerical model of the platform is tuned and validated by ANSYS AQWA according to the model test results. With the support of the tuned numerical model, seventeen simulation cases about the presented platform are considered to study the wave, wind, and current loads simultaneously. Then, the impact analysis studies of air gap motion regarding the length, elasticity, and type of the mooring line are performed in the time domain under the beam wave, head wave, and oblique wave conditions.

  19. The Challenges Facing School Governing Bodies in England: A "Perfect Storm"?

    ERIC Educational Resources Information Center

    James, Chris; Brammer, Steve; Connolly, Michael; Spicer, David Eddy; James, Jane; Jones, Jeff

    2013-01-01

    The governing bodies of publicly funded schools in England are currently facing a number of substantive challenges of various kinds. Many of the challenges are long-standing, while others relate to the current context for governing wrought by recent education policy developments initiated by central government. A number of the challenges are…

  20. [Research progress on real-time deformable models of soft tissues for surgery simulation].

    PubMed

    Xu, Shaoping; Liu, Xiaoping; Zhang, Hua; Luo, Jie

    2010-04-01

    Biological tissues generally exhibit nonlinearity, anisotropy, quasi-incompressibility and viscoelasticity about material properties. Simulating the behaviour of elastic objects in real time is one of the current objectives of virtual surgery simulation which is still a challenge for researchers to accurately depict the behaviour of human tissues. In this paper, we present a classification of the different deformable models that have been developed. We present the advantages and disadvantages of each one. Finally, we make a comparison of deformable models and perform an evaluation of the state of the art and the future of deformable models.

  1. Unified Deep Learning Architecture for Modeling Biology Sequence.

    PubMed

    Wu, Hongjie; Cao, Chengyuan; Xia, Xiaoyan; Lu, Qiang

    2017-10-09

    Prediction of the spatial structure or function of biological macromolecules based on their sequence remains an important challenge in bioinformatics. When modeling biological sequences using traditional sequencing models, characteristics, such as long-range interactions between basic units, the complicated and variable output of labeled structures, and the variable length of biological sequences, usually lead to different solutions on a case-by-case basis. This study proposed the use of bidirectional recurrent neural networks based on long short-term memory or a gated recurrent unit to capture long-range interactions by designing the optional reshape operator to adapt to the diversity of the output labels and implementing a training algorithm to support the training of sequence models capable of processing variable-length sequences. Additionally, the merge and pooling operators enhanced the ability to capture short-range interactions between basic units of biological sequences. The proposed deep-learning model and its training algorithm might be capable of solving currently known biological sequence-modeling problems through the use of a unified framework. We validated our model on one of the most difficult biological sequence-modeling problems currently known, with our results indicating the ability of the model to obtain predictions of protein residue interactions that exceeded the accuracy of current popular approaches by 10% based on multiple benchmarks.

  2. A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models.

    PubMed

    Asaad, Mazen; Lee, Jin Hyung

    2018-05-18

    Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. © 2018. Published by The Company of Biologists Ltd.

  3. A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models

    PubMed Central

    Asaad, Mazen

    2018-01-01

    ABSTRACT Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. PMID:29784664

  4. Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

    PubMed Central

    Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe

    2011-01-01

    Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126

  5. Zika virus vaccines: immune response, current status, and future challenges.

    PubMed

    Richner, Justin M; Diamond, Michael S

    2018-05-09

    Zika virus (ZIKV) is the most recent mosquito-transmitted virus to cause a global health crisis following its entrance into a naïve population in the Western Hemisphere. Once the ZIKV outbreak began investigators rapidly established small and large animal models of pathogenesis, developed a number candidate vaccines using different platforms, and defined mechanisms of protection. In this review, we characterize the adaptive immune response elicited by ZIKV infections and vaccines, the status of ongoing clinical trials in humans, and discuss future challenges within the field. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Reactivity Insertion Accident (RIA) Capability Status in the BISON Fuel Performance Code

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Williamson, Richard L.; Folsom, Charles Pearson; Pastore, Giovanni

    2016-05-01

    One of the Challenge Problems being considered within CASL relates to modelling and simulation of Light Water Reactor LWR) fuel under Reactivity Insertion Accident (RIA) conditions. BISON is the fuel performance code used within CASL for LWR fuel under both normal operating and accident conditions, and thus must be capable of addressing the RIA challenge problem. This report outlines required BISON capabilities for RIAs and describes the current status of the code. Information on recent accident capability enhancements, application of BISON to a RIA benchmark exercise, and plans for validation to RIA behavior are included.

  7. Clean Energy Finance: Challenges and Opportunities of Early-Stage Energy Investing (Presentation)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heap, D.; Pless, J.; Aieta, N.

    Characterized by a changing landscape and new opportunities, today's increasingly complex energy decision space will need innovative financing and investment models to appropriately assess risk and profitability. This report provides an overview of the current state of clean energy finance across the entire spectrum but with a focus on early stage investing, and it includes insights from investors across all investment classes. Further, this report aims to provide a roadmap with the mechanisms, limitations, and considerations involved in making successful investments by identifying risks, challenges, and opportunities in the clean energy sector.

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

    NASA Astrophysics Data System (ADS)

    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 current hydrological conditions, flood potential and the state of drought. Seasonal climate model forecasts are downscaled and bias-corrected to drive the land surface model to provide hydrological forecasts and drought products out 6-9 months. The system relies on historic reconstructions of water variability over the 20th century, which forms the background climatology to which current conditions can be assessed. Future changes in water availability and drought risk are quantified based on bias-corrected and downscaled climate model projections that are used to drive the land surface models. For regions with lack of on-the-ground data we are field-testing low-cost environmental sensors and along with new satellite products for terrestrial hydrology and vegetation, integrating these into the system for improved monitoring and prediction. At every step there are scientific challenges whose solutions are only partially being solved. In addition there are challenges in delivering such systems as "climate services", especially to societies with low technical capacity such as rural agriculturalists in sub-Saharan Africa, but whose needs for such information are great. We provide an overview of the system and some examples of real-world applications to flood and drought events, with a focus on Africa.

  9. The social and political lives of zoonotic disease models: narratives, science and policy.

    PubMed

    Leach, Melissa; Scoones, Ian

    2013-07-01

    Zoonotic diseases currently pose both major health threats and complex scientific and policy challenges, to which modelling is increasingly called to respond. In this article we argue that the challenges are best met by combining multiple models and modelling approaches that elucidate the various epidemiological, ecological and social processes at work. These models should not be understood as neutral science informing policy in a linear manner, but as having social and political lives: social, cultural and political norms and values that shape their development and which they carry and project. We develop and illustrate this argument in relation to the cases of H5N1 avian influenza and Ebola, exploring for each the range of modelling approaches deployed and the ways they have been co-constructed with a particular politics of policy. Addressing the complex, uncertain dynamics of zoonotic disease requires such social and political lives to be made explicit in approaches that aim at triangulation rather than integration, and plural and conditional rather than singular forms of policy advice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The Diagnostic Challenge Competition: Probabilistic Techniques for Fault Diagnosis in Electrical Power Systems

    NASA Technical Reports Server (NTRS)

    Ricks, Brian W.; Mengshoel, Ole J.

    2009-01-01

    Reliable systems health management is an important research area of NASA. A health management system that can accurately and quickly diagnose faults in various on-board systems of a vehicle will play a key role in the success of current and future NASA missions. We introduce in this paper the ProDiagnose algorithm, a diagnostic algorithm that uses a probabilistic approach, accomplished with Bayesian Network models compiled to Arithmetic Circuits, to diagnose these systems. We describe the ProDiagnose algorithm, how it works, and the probabilistic models involved. We show by experimentation on two Electrical Power Systems based on the ADAPT testbed, used in the Diagnostic Challenge Competition (DX 09), that ProDiagnose can produce results with over 96% accuracy and less than 1 second mean diagnostic time.

  11. Vulnerable Population Challenges in the Transformation of Cancer Care.

    PubMed

    Meneses, Karen; Landier, Wendy; Dionne-Odom, J Nicholas

    2016-05-01

    To consider current trends and future strategies that will bring about change in cancer care delivery for vulnerable populations. Institute of Medicine reports, literature review, clinical practice observations and experiences. Vulnerable populations are older adults, both minorities and the underserved, children, and individuals at end of life. These groups pose unique challenges that require health system changes and innovative nursing models to assure access to patient-centered care in the future. In the future, attention to the needs of vulnerable populations, the growing aging cancer population and the improved outcomes in the pediatric and adolescent cancer population will all require new nursing services and models of care. System changes where nursing roles are critical to support the transition to earlier palliative care are projected. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Reforming funding for chronic illness: Medicare-CDM.

    PubMed

    Swerissen, Hal; Taylor, Michael J

    2008-02-01

    Chronic diseases are a major challenge for the Australian health care system in terms of both the provision of quality care and expenditure, and these challenges will only increase in the future. Various programs have been instituted under the Medicare system to provide increased funding for chronic care, but essentially these programs still follow the traditional fee-for-service model. This paper proposes a realignment and extension of current Medicare chronic disease management programs into a framework that provides general practitioners and other health professionals with the necessary "tools" for high quality care planning and ongoing management, and incorporating international models of outcome-linked funding. The integration of social support services with the Medicare system is also a necessary step in providing high quality care for patients with complex needs requiring additional support.

  13. Management of pain in patients with temporomandibular disorder (TMD): challenges and solutions

    PubMed Central

    Gil-Martínez, Alfonso; Paris-Alemany, Alba; López-de-Uralde-Villanueva, Ibai; La Touche, Roy

    2018-01-01

    Thanks to advances in neuroscience, biopsychosocial models for diagnostics and treatment (including physical, psychological, and pharmacological therapies) currently have more clinical support and scientific growth. At present, a conservative treatment approach prevails over surgery, given it is less aggressive and usually results in satisfactory clinical outcomes in mild–moderate temporomandibular disorder (TMD). The aim of this review is to evaluate the recent evidence, identify challenges, and propose solutions from a clinical point of view for patients with craniofacial pain and TMD. The treatment we propose is structured in a multi-modal approach based on a biobehavioral approach that includes medical, physiotherapeutic, psychological, and dental treatments. We also propose a new biobehavioral model regarding pain perception and motor behavior for the diagnosis and treatment of patients with painful TMD. PMID:29588615

  14. Model-based reasoning in SSF ECLSS

    NASA Technical Reports Server (NTRS)

    Miller, J. K.; Williams, George P. W., Jr.

    1992-01-01

    The interacting processes and reconfigurable subsystems of the Space Station Freedom Environmental Control and Life Support System (ECLSS) present a tremendous technical challenge to Freedom's crew and ground support. ECLSS operation and problem analysis is time-consuming for crew members and difficult for current computerized control, monitoring, and diagnostic software. These challenges can be at least partially mitigated by the use of advanced techniques such as Model-Based Reasoning (MBR). This paper will provide an overview of MBR as it is being applied to Space Station Freedom ECLSS. It will report on work being done to produce intelligent systems to help design, control, monitor, and diagnose Freedom's ECLSS. Specifically, work on predictive monitoring, diagnosability, and diagnosis, with emphasis on the automated diagnosis of the regenerative water recovery and air revitalization processes will be discussed.

  15. Challenges in Drug Discovery for Neurofibromatosis Type 1-Associated Low-Grade Glioma

    PubMed Central

    Ricker, Cora A.; Pan, Yuan; Gutmann, David H.; Keller, Charles

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that results from germline mutations of the NF1 gene, creating a predisposition to low-grade gliomas (LGGs; pilocytic astrocytoma) in young children. Insufficient data and resources represent major challenges to identifying the best possible drug therapies for children with this tumor. Herein, we summarize the currently available cell lines, genetically engineered mouse models, and therapeutic targets for these LGGs. Conspicuously absent are human tumor-derived cell lines or patient-derived xenograft models for NF1-LGG. New collaborative initiatives between patients and their families, research groups, and pharmaceutical companies are needed to create transformative resources and broaden the knowledge base relevant to identifying cooperating genetic drivers and possible drug therapeutics for this common pediatric brain tumor. PMID:28066715

  16. Restoring Psychology's Role in Peptic Ulcer

    PubMed Central

    Overmier, J Bruce; Murison, Robert

    2013-01-01

    This paper reviews the history of the transition from the belief that gastrointestinal ulcers are caused primarily by psychological factors to the current state of belief that they are caused primarily by infection and argues that neither is fully accurate. We argue that psychological factors play a significant role as predisposing to vulnerability, modulating of precipitation, and sustaining of gastric ulceration. We review data that challenge the assumption of a simple infectious disease model and adduce recent preclinical data that confirm the predisposing, modulatory, and sustaining roles for psychological factors. We note that others, too, are now challenging the adequacy of the contemporary simple bacterial infection model. We hope to replace the competition between psychology and medicine with cooperation in understanding and treating patients suffering gastric ulceration and ulcer. PMID:23457084

  17. The Challenge of Simulating the Regional Climate over Florida

    NASA Astrophysics Data System (ADS)

    Misra, V.; Mishra, A. K.

    2015-12-01

    In this study we show that the unique geography of the peninsular Florida with close proximity to strong mesoscale surface ocean currents among other factors warrants the use of relatively high resolution climate models to project Florida's hydroclimate. In the absence of such high resolution climate models we highlight the deficiencies of two relatively coarse spatial resolution CMIP5 models with respect to the warm western boundary current of the Gulf Stream. As a consequence it affects the coastal SST and the land-ocean contrast, affecting the rainy summer seasonal precipitation accumulation over peninsular Florida. We also show this through two sensitivity studies conducted with a regional coupled ocean atmosphere model with different bathymetries that dislocate and modulate the strength of the Gulf Stream that locally affects the SST in the two simulations. These studies show that a stronger and more easterly displaced Gulf Stream produces warmer coastal SST's along the Atlantic coast of Florida that enhances the precipitation over peninsular Florida relative to the other regional climate model simulation. However the regional model simulations indicate that variability of wet season rainfall variability in peninsular Florida becomes less dependent on the land-ocean contrast with a stronger Gulf Stream current.

  18. Hospital-Based Comparative Effectiveness Centers: Translating Research into Practice to Improve the Quality, Safety and Value of Patient Care

    PubMed Central

    Williams, Kendal; Brennan, Patrick J.

    2010-01-01

    Hospital-based comparative effectiveness (CE) centers provide a model that clinical leaders can use to improve evidence-based practice locally. The model is used by integrated health systems outside the US, but is less recognized in the US. Such centers can identify and adapt national evidence-based policies for the local setting, create local evidence-based policies in the absence of national policies, and implement evidence into practice through health information technology (HIT) and quality initiatives. Given the increasing availability of CE evidence and incentives to meaningfully use HIT, the relevance of this model to US practitioners is increasing. This is especially true in the context of healthcare reform, which will likely reduce reimbursements for care deemed unnecessary by published evidence or guidelines. There are challenges to operating hospital-based CE centers, but many of these challenges can be overcome using solutions developed by those currently leading such centers. In conclusion, these centers have the potential to improve the quality, safety and value of care locally, ultimately translating into higher quality and more cost-effective care nationally. To better understand this potential, the current activity and impact of hospital-based CE centers in the US should be rigorously examined. PMID:20697961

  19. In Vitro Cerebrovascular Modeling in the 21st Century: Current and Prospective Technologies

    PubMed Central

    Palmiotti, Christopher A.; Prasad, Shikha; Naik, Pooja; Abul, Kaisar MD; Sajja, Ravi K.; Achyuta, Anilkumar H.; Cucullo, Luca

    2014-01-01

    The blood-brain barrier (BBB) maintains the brain homeostasis and dynamically responds to events associated with systemic and/or rheological impairments (e.g., inflammation, ischemia) including the exposure to harmful xenobiotics. Thus, understanding the BBB physiology is crucial for the resolution of major central nervous system CNS) disorders challenging both health care providers and the pharmaceutical industry. These challenges include drug delivery to the brain, neurological disorders, toxicological studies, and biodefense. Studies aimed at advancing our understanding of CNS diseases and promoting the development of more effective therapeutics are primarily performed in laboratory animals. However, there are major hindering factors inherent to in vivo studies such as cost, limited throughput and translational significance to humans. These factors promoted the development of alternative in vitro strategies for studying the physiology and pathophysiology of the BBB in relation to brain disorders as well as screening tools to aid in the development of novel CNS drugs. Herein, we provide a detailed review including pros and cons of current and prospective technologies for modelling the BBB in vitro including ex situ, cell based and computational (in silico) models. A special section is dedicated to microfluidic systems including micro-BBB, BBB-on-a-chip, Neurovascular Unit-on-a-Chip and Synthetic Microvasculature Blood-Brain Barrier. PMID:25098812

  20. In vitro cerebrovascular modeling in the 21st century: current and prospective technologies.

    PubMed

    Palmiotti, Christopher A; Prasad, Shikha; Naik, Pooja; Abul, Kaisar M D; Sajja, Ravi K; Achyuta, Anilkumar H; Cucullo, Luca

    2014-12-01

    The blood-brain barrier (BBB) maintains the brain homeostasis and dynamically responds to events associated with systemic and/or rheological impairments (e.g., inflammation, ischemia) including the exposure to harmful xenobiotics. Thus, understanding the BBB physiology is crucial for the resolution of major central nervous system CNS) disorders challenging both health care providers and the pharmaceutical industry. These challenges include drug delivery to the brain, neurological disorders, toxicological studies, and biodefense. Studies aimed at advancing our understanding of CNS diseases and promoting the development of more effective therapeutics are primarily performed in laboratory animals. However, there are major hindering factors inherent to in vivo studies such as cost, limited throughput and translational significance to humans. These factors promoted the development of alternative in vitro strategies for studying the physiology and pathophysiology of the BBB in relation to brain disorders as well as screening tools to aid in the development of novel CNS drugs. Herein, we provide a detailed review including pros and cons of current and prospective technologies for modelling the BBB in vitro including ex situ, cell based and computational (in silico) models. A special section is dedicated to microfluidic systems including micro-BBB, BBB-on-a-chip, Neurovascular Unit-on-a-Chip and Synthetic Microvasculature Blood-brain Barrier.

  1. MobileODT: a case study of a novel approach to an mHealth-based model of sustainable impact

    PubMed Central

    Mink, Jonah

    2016-01-01

    A persistent challenge facing global health actors is ensuring that time-bound interventions are ultimately adopted and integrated into local health systems for long term health system strengthening and capacity building. This level of sustainability is rarely achieved with current models of global health intervention that rely on continuous injection of resources or persistent external presence on the ground. Presented here is a case study of a flipped approach to creating capacity and adoption through an engagement strategy centered around an innovative mHealth device and connected service. Through an impact-oriented business model, this mHealth solution engages stakeholders in a cohesive and interdependent network by appealing to the pain points for each actor throughout the health system. This particular intervention centers around the MobileODT, Inc. Enhanced Visual Assessment (EVA) System for enhanced visualization. While focused on challenges to cervical cancer screening and treatment services, the lessons learned are offered as a model for lateral translation into adjacent health condition verticals. PMID:28293590

  2. Theoretical models for coronary vascular biomechanics: Progress & challenges

    PubMed Central

    Waters, Sarah L.; Alastruey, Jordi; Beard, Daniel A.; Bovendeerd, Peter H.M.; Davies, Peter F.; Jayaraman, Girija; Jensen, Oliver E.; Lee, Jack; Parker, Kim H.; Popel, Aleksander S.; Secomb, Timothy W.; Siebes, Maria; Sherwin, Spencer J.; Shipley, Rebecca J.; Smith, Nicolas P.; van de Vosse, Frans N.

    2013-01-01

    A key aim of the cardiac Physiome Project is to develop theoretical models to simulate the functional behaviour of the heart under physiological and pathophysiological conditions. Heart function is critically dependent on the delivery of an adequate blood supply to the myocardium via the coronary vasculature. Key to this critical function of the coronary vasculature is system dynamics that emerge via the interactions of the numerous constituent components at a range of spatial and temporal scales. Here, we focus on several components for which theoretical approaches can be applied, including vascular structure and mechanics, blood flow and mass transport, flow regulation, angiogenesis and vascular remodelling, and vascular cellular mechanics. For each component, we summarise the current state of the art in model development, and discuss areas requiring further research. We highlight the major challenges associated with integrating the component models to develop a computational tool that can ultimately be used to simulate the responses of the coronary vascular system to changing demands and to diseases and therapies. PMID:21040741

  3. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    PubMed Central

    Seah, Yu Fen Samantha; EL Farran, Chadi A.; Warrier, Tushar; Xu, Jian; Loh, Yuin-Han

    2015-01-01

    Embryonic stem cells (ESCs) are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs) via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases. PMID:26633382

  4. Reduction of collisional-radiative models for transient, atomic plasmas

    NASA Astrophysics Data System (ADS)

    Abrantes, Richard June; Karagozian, Ann; Bilyeu, David; Le, Hai

    2017-10-01

    Interactions between plasmas and any radiation field, whether by lasers or plasma emissions, introduce many computational challenges. One of these computational challenges involves resolving the atomic physics, which can influence other physical phenomena in the radiated system. In this work, a collisional-radiative (CR) model with reduction capabilities is developed to capture the atomic physics at a reduced computational cost. Although the model is made with any element in mind, the model is currently supplemented by LANL's argon database, which includes the relevant collisional and radiative processes for all of the ionic stages. Using the detailed data set as the true solution, reduction mechanisms in the form of Boltzmann grouping, uniform grouping, and quasi-steady-state (QSS), are implemented to compare against the true solution. Effects on the transient plasma stemming from the grouping methods are compared. Distribution A: Approved for public release; unlimited distribution, PA (Public Affairs) Clearance Number 17449. This work was supported by the Air Force Office of Scientific Research (AFOSR), Grant Number 17RQCOR463 (Dr. Jason Marshall).

  5. Management of Leigh syndrome: Current status and new insights.

    PubMed

    Chen, L; Cui, Y; Jiang, D; Ma, C Y; Tse, H-F; Hwu, W-L; Lian, Q

    2018-06-01

    Leigh syndrome (LS) is an inherited mitochondrial encephalopathy associated with gene mutations of oxidative phosphorylation pathway that result in early disability and death in affected young children. Currently, LS is incurable and unresponsive to many treatments, although some case reports indicate that supplements can improve the condition. Many novel therapies are being continuously tested in pre-clinical studies. In this review, we summarize the genetic basis of LS, current treatment, pre-clinical studies in animal models and the management of other mitochondrial diseases. Future therapeutical strategies and challenges are also discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Remote Sensing of Drought: Progress and Opportunities for Improving Drought Monitoring and Prediction

    NASA Astrophysics Data System (ADS)

    AghaKouchak, A.; Huning, L. S.; Love, C. A.; Farahmand, A.

    2017-12-01

    This presentation surveys current and emerging drought monitoring approaches using satellite remote sensing observations from climatological and ecosystem perspectives. Satellite observations that are not currently used for operational drought monitoring, such as near-surface air relative humidity and water vapor, provide opportunities to improve early drought warning. Current and future satellite missions offer opportunities to develop composite and multi-indicator drought models. This presentation describes how different satellite observations can be combined for overall drought development and impact assessment. Finally, we provide an overview of the research gaps and challenges that are facing us ahead in the remote sensing of drought.

  7. Cygnus X-1: A Case for a Magnetic Accretion Disk?

    NASA Technical Reports Server (NTRS)

    Nowak, Michael A.; Vaughan, B. A.; Dove, J.; Wilms, J.

    1996-01-01

    With the advent of Rossi X-ray Timing Explorer (RXTE), which is capable of broad spectral coverage and fast timing, as well as other instruments which are increasingly being used in multi-wavelength campaigns (via both space-based and ground-based observations), we must demand more of our theoretical models. No current model mimics all facets of a system as complex as an x-ray binary. However, a modern theory should qualitatively reproduce - or at the very least not fundamentally disagree with - all of Cygnus X-l's most basic average properties: energy spectrum (viewed within a broader framework of black hole candidate spectral behavior), power spectrum (PSD), and time delays and coherence between variability in different energy bands. Below we discuss each of these basic properties in turn, and we assess the health of one of the currently popular theories: Comptonization of photons from a cold disk. We find that the data pose substantial challenges for this theory, as well as all other in currently discussed models.

  8. An analytical-numerical approach for parameter determination of a five-parameter single-diode model of photovoltaic cells and modules

    NASA Astrophysics Data System (ADS)

    Hejri, Mohammad; Mokhtari, Hossein; Azizian, Mohammad Reza; Söder, Lennart

    2016-04-01

    Parameter extraction of the five-parameter single-diode model of solar cells and modules from experimental data is a challenging problem. These parameters are evaluated from a set of nonlinear equations that cannot be solved analytically. On the other hand, a numerical solution of such equations needs a suitable initial guess to converge to a solution. This paper presents a new set of approximate analytical solutions for the parameters of a five-parameter single-diode model of photovoltaic (PV) cells and modules. The proposed solutions provide a good initial point which guarantees numerical analysis convergence. The proposed technique needs only a few data from the PV current-voltage characteristics, i.e. open circuit voltage Voc, short circuit current Isc and maximum power point current and voltage Im; Vm making it a fast and low cost parameter determination technique. The accuracy of the presented theoretical I-V curves is verified by experimental data.

  9. Regulation of stem cell-based therapies in Canada: current issues and concerns.

    PubMed

    von Tigerstrom, Barbara; Nguyen, Thu Minh; Knoppers, Bartha Maria

    2012-09-01

    Stem cell therapies offer enormous potential for the treatment of a wide range of diseases and conditions. Despite the excitement over such advances, regulators are faced with the challenge of determining criteria to ensure stem cells and their products are safe and effective for human use. However, stem cell-based products and therapies present unique regulatory challenges because standard drug development models do not wholly apply given the complexity and diversity of these products and therapies. As a result, regulatory requirements are often unclear and ambiguous creating unnecessary barriers for research. In order to better understand the barriers that might affect Canadian stem cell researchers, we sought feedback from stakeholders regarding areas of uncertainty or concern about existing regulatory oversight of cell therapies. A selection of Canadian researchers and clinicians working in the area of stem cell research were interviewed to assess certain key questions: 1) whether current regulatory requirements are easily accessible and well understood; 2) whether regulatory requirements create important challenges or barriers; and 3) whether there is a need for further guidance on the issue. The results of this survey are summarized and compared to issues and concerns experienced in other countries, as reported in the literature, to identify challenges which may be on the horizon and to provide possible solutions for regulatory reform.

  10. Identifying and Overcoming Threshold Concepts and Conceptions: Introducing a Conception-Focused Curriculum to Course Design

    ERIC Educational Resources Information Center

    Burch, Gerald F.; Burch, Jana J.; Bradley, Thomas P.; Heller, Nathan A.

    2015-01-01

    Educators have been challenged to identify threshold concepts and develop transformed students. This stands in stark contrast to many curriculum design and delivery models that currently view students as repositories of knowledge. In this article, we argue that educators can reach both goals, identify stumbling blocks and transforming students,…

  11. Supporting International Applicants and Promoting an Ethical Model of Global College Admission

    ERIC Educational Resources Information Center

    Redding, Alexis Brooke

    2013-01-01

    This article examines the challenges facing the pool of global applicants to US colleges and evaluates the practices of the internationaI IECs who currently fill the void that exists between applicants and admission officers. The author, is a doctoral student at the Harvard Graduate School of Education, where she researches ethical issues in…

  12. Large-Scale Innovation and Change in UK Higher Education

    ERIC Educational Resources Information Center

    Brown, Stephen

    2013-01-01

    This paper reflects on challenges universities face as they respond to change. It reviews current theories and models of change management, discusses why universities are particularly difficult environments in which to achieve large scale, lasting change and reports on a recent attempt by the UK JISC to enable a range of UK universities to employ…

  13. Global Times Call for Global Measures: Investigating Automated Essay Scoring in Linguistically-Diverse MOOCs

    ERIC Educational Resources Information Center

    Reilly, Erin D.; Williams, Kyle M.; Stafford, Rose E.; Corliss, Stephanie B.; Walkow, Janet C.; Kidwell, Donna K.

    2016-01-01

    This paper utilizes a case-study design to discuss global aspects of massive open online course (MOOC) assessment. Drawing from the literature on open-course models and linguistic gatekeeping in education, we position freeform assessment in MOOCs as both challenging and valuable, with an emphasis on current practices and student resources. We…

  14. Global Rankings in the Nordic Region: Challenging the Identity of Research-Intensive Universities?

    ERIC Educational Resources Information Center

    Elken, Mari; Hovdhaugen, Elisabeth; Stensaker, Bjørn

    2016-01-01

    Global university rankings currently attract considerable attention, and it is often assumed that such rankings may cause universities to prioritize activities and outcomes that will have a positive effect in their ranking position. A possible consequence of this could be the spread of a particular model of an "ideal" university. This…

  15. Learning Experiences Reuse Based on an Ontology Modeling to Improve Adaptation in E-Learning Systems

    ERIC Educational Resources Information Center

    Hadj M'tir, Riadh; Rumpler, Béatrice; Jeribi, Lobna; Ben Ghezala, Henda

    2014-01-01

    Current trends in e-Learning focus mainly on personalizing and adapting the learning environment and learning process. Although their increasingly number, theses researches often ignore the concepts of capitalization and reuse of learner experiences which can be exploited later by other learners. Thus, the major challenge of distance learning is…

  16. Double Infusion: Toward a Process of Articulation between Critical Multicultural Education and Technology Education in a Teacher Preparation Program

    ERIC Educational Resources Information Center

    McShay, James

    2005-01-01

    This paper describes the goals of critical multicultural education in the USA and identifies current challenges working to impede its infusion within technology teacher education programs. It offers both technology and multicultural teacher educators a model for infusion of both critical multicultural perspectives and technology into their…

  17. Entrepreneurship Education in Malaysia's Public Institutions of Higher Learning--A Review of the Current Practices

    ERIC Educational Resources Information Center

    Bin Yusoff, Mohd Nor Hakimin; Zainol, Fakhrul Anwar; Bin Ibrahim, Mohamed Dahlan

    2015-01-01

    The need for a practical and applicable model for entrepreneurial learning is becoming critical. In this study, we aimed to collect data related to entrepreneurship education practices by all institutes of higher learning (IHLs) in Malaysia as well as challenges faced, facilities, and supports offered by the universities. Given the important role…

  18. Rethinking the Urban School Superintendency: Nontraditional Leaders and New Models of Leadership.

    ERIC Educational Resources Information Center

    Usdan, Michael D.; Cronin, Joseph M.

    This paper discusses the 21st century urban school superintendency, noting new challenges for urban superintendents. Currently, schools are much larger, media coverage is extensive, racial minorities settle most often in the city, and cities cope with vast social problems. School boards have an enormous effect on the success or failure of…

  19. ADHD and Working Memory: The Impact of Central Executive Deficits and Exceeding Storage/Rehearsal Capacity on Observed Inattentive Behavior

    ERIC Educational Resources Information Center

    Kofler, Michael J.; Rapport, Mark D.; Bolden, Jennifer; Sarver, Dustin E.; Raiker, Joseph S.

    2010-01-01

    Inattentive behavior is considered a core and pervasive feature of ADHD; however, an alternative model challenges this premise and hypothesizes a functional relationship between working memory deficits and inattentive behavior. The current study investigated whether inattentive behavior in children with ADHD is functionally related to the…

  20. On the Relationship between Society and Higher Education: What Path Should We Take?

    ERIC Educational Resources Information Center

    Márquez-Ramos, Laura; Mourelle, Estefanía

    2018-01-01

    The current network society, with its primacy of information and communication technologies, is challenging the higher education model. The needs and expectations of today's students differ from those of students in the past, and educational practices should adapt to modern times. But what changes will we see in the relationship between societal…

  1. An Examination of Factors Influencing Students Selection of Business Majors Using TRA Framework

    ERIC Educational Resources Information Center

    Kumar, Anil; Kumar, Poonam

    2013-01-01

    Making decisions regarding the selection of a business major is both very important and challenging for students. An understanding of this decision-making process can be valuable for students, parents, and university programs. The current study applies the Theory of Reasoned Action (TRA) consumer decision-making model to examine factors that…

  2. The Battle over Professorship: Reform of Human Resource Management and Academic Careers in a Comparative Perspective

    ERIC Educational Resources Information Center

    Majcher, Agnieszka

    2008-01-01

    Changing conditions of academic and scientific labour markets challenge the current conceptual thinking about the mechanisms of academic promotion, selection and recruitment. This paper explores the models of academic promotion and recruitment of professors in a comparative perspective using the examples of Poland and Germany, and addresses the…

  3. Computational challenges in atomic, molecular and optical physics.

    PubMed

    Taylor, Kenneth T

    2002-06-15

    Six challenges are discussed. These are the laser-driven helium atom; the laser-driven hydrogen molecule and hydrogen molecular ion; electron scattering (with ionization) from one-electron atoms; the vibrational and rotational structure of molecules such as H(3)(+) and water at their dissociation limits; laser-heated clusters; and quantum degeneracy and Bose-Einstein condensation. The first four concern fundamental few-body systems where use of high-performance computing (HPC) is currently making possible accurate modelling from first principles. This leads to reliable predictions and support for laboratory experiment as well as true understanding of the dynamics. Important aspects of these challenges addressable only via a terascale facility are set out. Such a facility makes the last two challenges in the above list meaningfully accessible for the first time, and the scientific interest together with the prospective role for HPC in these is emphasized.

  4. Discovery of innovative therapeutics: today's realities and tomorrow's vision. 1. Criticisms faced by the pharmaceutical industry.

    PubMed

    Abou-Gharbia, Magid; Childers, Wayne E

    2013-07-25

    The pharmaceutical industry is facing enormous challenges, including reduced efficiency, declining innovation, key patent expirations, fierce price competition from generics, high regulatory hurdles, and a tarnished image. There is a clear need for change in the paradigms designed to address these challenges. Pharma has responded by embarking on a range of initiatives. However, along the way the industry has accrued critics whose accusations have tainted its reputation. The first part of this two-part series will discuss the criticisms that have been leveled at the pharmaceutical industry and summarize the supporting data for and against these criticisms. The second installment will focus on the current challenges facing the pharmaceutical industry and Pharma's responses to address these challenges. It will describe the industry's changing perspective and new business models for coping with the recent loss of talent and declining clinical pipelines as well as present some examples of recent drug discovery successes.

  5. The State and Future of the Primary Care Behavioral Health Model of Service Delivery Workforce.

    PubMed

    Serrano, Neftali; Cordes, Colleen; Cubic, Barbara; Daub, Suzanne

    2018-06-01

    The growth of the Primary Care Behavioral Health model (PCBH) nationally has highlighted and created a workforce development challenge given that most mental health professionals are not trained for primary care specialization. This work provides a review of the current efforts to retrain mental health professionals to fulfill roles as Behavioral Health Consultants (BHCs) including certificate programs, technical assistance programs, literature and on-the-job training, as well as detail the future needs of the workforce if the model is to sustainably proliferate. Eight recommendations are offered including: (1) the development of an interprofessional certification body for PCBH training criteria, (2) integration of PCBH model specific curricula in graduate studies, (3) integration of program development skill building in curricula, (4) efforts to develop faculty for PCBH model awareness, (5) intentional efforts to draw students to graduate programs for PCBH model training, (6) a national employment clearinghouse, (7) efforts to coalesce current knowledge around the provision of technical assistance to sites, and (8) workforce specific research efforts.

  6. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DOE PAGES

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.; ...

    2017-01-18

    Currently, Constraint-Based Reconstruction and Analysis (COBRA) is the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Furthermore, standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger). We also developed a quadrupleprecision version of ourmore » linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data.« less

  7. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    Currently, Constraint-Based Reconstruction and Analysis (COBRA) is the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Furthermore, standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger). We also developed a quadrupleprecision version of ourmore » linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data.« less

  8. Heat Transfer Analysis in Wire Bundles for Aerospace Vehicles

    NASA Technical Reports Server (NTRS)

    Rickman, S. L.; Iamello, C. J.

    2016-01-01

    Design of wiring for aerospace vehicles relies on an understanding of "ampacity" which refers to the current carrying capacity of wires, either, individually or in wire bundles. Designers rely on standards to derate allowable current flow to prevent exceedance of wire temperature limits due to resistive heat dissipation within the wires or wire bundles. These standards often add considerable margin and are based on empirical data. Commercial providers are taking an aggressive approach to wire sizing which challenges the conventional wisdom of the established standards. Thermal modelling of wire bundles may offer significant mass reduction in a system if the technique can be generalized to produce reliable temperature predictions for arbitrary bundle configurations. Thermal analysis has been applied to the problem of wire bundles wherein any or all of the wires within the bundle may carry current. Wire bundles present analytical challenges because the heat transfer path from conductors internal to the bundle is tortuous, relying on internal radiation and thermal interface conductance to move the heat from within the bundle to the external jacket where it can be carried away by convective and radiative heat transfer. The problem is further complicated by the dependence of wire electrical resistivity on temperature. Reduced heat transfer out of the bundle leads to higher conductor temperatures and, hence, increased resistive heat dissipation. Development of a generalized wire bundle thermal model is presented and compared with test data. The steady state heat balance for a single wire is derived and extended to the bundle configuration. The generalized model includes the effects of temperature varying resistance, internal radiation and thermal interface conductance, external radiation and temperature varying convective relief from the free surface. The sensitivity of the response to uncertainties in key model parameters is explored using Monte Carlo analysis.

  9. Integrating Visualizations into Modeling NEST Simulations

    PubMed Central

    Nowke, Christian; Zielasko, Daniel; Weyers, Benjamin; Peyser, Alexander; Hentschel, Bernd; Kuhlen, Torsten W.

    2015-01-01

    Modeling large-scale spiking neural networks showing realistic biological behavior in their dynamics is a complex and tedious task. Since these networks consist of millions of interconnected neurons, their simulation produces an immense amount of data. In recent years it has become possible to simulate even larger networks. However, solutions to assist researchers in understanding the simulation's complex emergent behavior by means of visualization are still lacking. While developing tools to partially fill this gap, we encountered the challenge to integrate these tools easily into the neuroscientists' daily workflow. To understand what makes this so challenging, we looked into the workflows of our collaborators and analyzed how they use the visualizations to solve their daily problems. We identified two major issues: first, the analysis process can rapidly change focus which requires to switch the visualization tool that assists in the current problem domain. Second, because of the heterogeneous data that results from simulations, researchers want to relate data to investigate these effectively. Since a monolithic application model, processing and visualizing all data modalities and reflecting all combinations of possible workflows in a holistic way, is most likely impossible to develop and to maintain, a software architecture that offers specialized visualization tools that run simultaneously and can be linked together to reflect the current workflow, is a more feasible approach. To this end, we have developed a software architecture that allows neuroscientists to integrate visualization tools more closely into the modeling tasks. In addition, it forms the basis for semantic linking of different visualizations to reflect the current workflow. In this paper, we present this architecture and substantiate the usefulness of our approach by common use cases we encountered in our collaborative work. PMID:26733860

  10. Next generation data systems and knowledge products to support agricultural producers and science-based policy decision making.

    PubMed

    Capalbo, Susan M; Antle, John M; Seavert, Clark

    2017-07-01

    Research on next generation agricultural systems models shows that the most important current limitation is data, both for on-farm decision support and for research investment and policy decision making. One of the greatest data challenges is to obtain reliable data on farm management decision making, both for current conditions and under scenarios of changed bio-physical and socio-economic conditions. This paper presents a framework for the use of farm-level and landscape-scale models and data to provide analysis that could be used in NextGen knowledge products, such as mobile applications or personal computer data analysis and visualization software. We describe two analytical tools - AgBiz Logic and TOA-MD - that demonstrate the current capability of farmlevel and landscape-scale models. The use of these tools is explored with a case study of an oilseed crop, Camelina sativa , which could be used to produce jet aviation fuel. We conclude with a discussion of innovations needed to facilitate the use of farm and policy-level models to generate data and analysis for improved knowledge products.

  11. Episodes of care: is emergency medicine ready?

    PubMed

    Wiler, Jennifer L; Beck, Dennis; Asplin, Brent R; Granovsky, Michael; Moorhead, John; Pilgrim, Randy; Schuur, Jeremiah D

    2012-05-01

    Optimizing resource use, eliminating waste, aligning provider incentives, reducing overall costs, and coordinating the delivery of quality care while improving outcomes have been major themes of health care reform initiatives. Recent legislation contains several provisions designed to move away from the current fee-for-service payment mechanism toward a model that reimburses providers for caring for a population of patients over time while shifting more financial risk to providers. In this article, we review current approaches to episode of care development and reimbursement. We describe the challenges of incorporating emergency medicine into the episode of care approach and the uncertain influence this delivery model will have on emergency medicine care, including quality outcomes. We discuss the limitations of the episode of care payment model for emergency services and advocate retention of the current fee-for-service payment model, as well as identify research gaps that, if addressed, could be used to inform future policy decisions of emergency medicine health policy leaders. We then describe a meaningful role for emergency medicine in an episode of care setting. Copyright © 2011. Published by Mosby, Inc.

  12. Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research

    PubMed Central

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinská, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Mælandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    2014-01-01

    Recently, there has been increasing interest in the development and characterization of patient derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histological and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. This paper summarizes the current state of the art in this field including methodological issues, available collections, practical applications, challenges and shortcoming, and future directions, and introduces a European consortium of PDX models. PMID:25185190

  13. A Review of the Application of Body-on-a-Chip for Drug Test and Its Latest Trend of Incorporating Barrier Tissue.

    PubMed

    Jin, Haoyi; Yu, Yanqiu

    2016-10-01

    High-quality preclinical bioassay models are essential for drug research and development. We reviewed the emerging body-on-a-chip technology, which serves as a promising model to overcome the limitations of traditional bioassay models, and introduced existing models of body-on-a-chip, their constitutional details, application for drug testing, and individual features of these models. We put special emphasis on the latest trend in this field of incorporating barrier tissue into body-on-a-chip and discussed several remaining challenges of current body-on-a-chip. © 2015 Society for Laboratory Automation and Screening.

  14. Optimal regeneration planning for old-growth forest: addressing scientific uncertainty in endangered species recovery through adaptive management

    USGS Publications Warehouse

    Moore, C.T.; Conroy, M.J.

    2006-01-01

    Stochastic and structural uncertainties about forest dynamics present challenges in the management of ephemeral habitat conditions for endangered forest species. Maintaining critical foraging and breeding habitat for the endangered red-cockaded woodpecker (Picoides borealis) requires an uninterrupted supply of old-growth forest. We constructed and optimized a dynamic forest growth model for the Piedmont National Wildlife Refuge (Georgia, USA) with the objective of perpetuating a maximum stream of old-growth forest habitat. Our model accommodates stochastic disturbances and hardwood succession rates, and uncertainty about model structure. We produced a regeneration policy that was indexed by current forest state and by current weight of evidence among alternative model forms. We used adaptive stochastic dynamic programming, which anticipates that model probabilities, as well as forest states, may change through time, with consequent evolution of the optimal decision for any given forest state. In light of considerable uncertainty about forest dynamics, we analyzed a set of competing models incorporating extreme, but plausible, parameter values. Under any of these models, forest silviculture practices currently recommended for the creation of woodpecker habitat are suboptimal. We endorse fully adaptive approaches to the management of endangered species habitats in which predictive modeling, monitoring, and assessment are tightly linked.

  15. What we can and cannot (yet) do with functional near infrared spectroscopy

    PubMed Central

    Strait, Megan; Scheutz, Matthias

    2014-01-01

    Functional near infrared spectroscopy (NIRS) is a relatively new technique complimentary to EEG for the development of brain-computer interfaces (BCIs). NIRS-based systems for detecting various cognitive and affective states such as mental and emotional stress have already been demonstrated in a range of adaptive human–computer interaction (HCI) applications. However, before NIRS-BCIs can be used reliably in realistic HCI settings, substantial challenges oncerning signal processing and modeling must be addressed. Although many of those challenges have been identified previously, the solutions to overcome them remain scant. In this paper, we first review what can be currently done with NIRS, specifically, NIRS-based approaches to measuring cognitive and affective user states as well as demonstrations of passive NIRS-BCIs. We then discuss some of the primary challenges these systems would face if deployed in more realistic settings, including detection latencies and motion artifacts. Lastly, we investigate the effects of some of these challenges on signal reliability via a quantitative comparison of three NIRS models. The hope is that this paper will actively engage researchers to acilitate the advancement of NIRS as a more robust and useful tool to the BCI community. PMID:24904261

  16. Modelling ventricular fibrillation coarseness during cardiopulmonary resuscitation by mixed effects stochastic differential equations.

    PubMed

    Gundersen, Kenneth; Kvaløy, Jan Terje; Eftestøl, Trygve; Kramer-Johansen, Jo

    2015-10-15

    For patients undergoing cardiopulmonary resuscitation (CPR) and being in a shockable rhythm, the coarseness of the electrocardiogram (ECG) signal is an indicator of the state of the patient. In the current work, we show how mixed effects stochastic differential equations (SDE) models, commonly used in pharmacokinetic and pharmacodynamic modelling, can be used to model the relationship between CPR quality measurements and ECG coarseness. This is a novel application of mixed effects SDE models to a setting quite different from previous applications of such models and where using such models nicely solves many of the challenges involved in analysing the available data. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Using natural selection and optimization for smarter vegetation models - challenges and opportunities

    NASA Astrophysics Data System (ADS)

    Franklin, Oskar; Han, Wang; Dieckmann, Ulf; Cramer, Wolfgang; Brännström, Åke; Pietsch, Stephan; Rovenskaya, Elena; Prentice, Iain Colin

    2017-04-01

    Dynamic global vegetation models (DGVMs) are now indispensable for understanding the biosphere and for estimating the capacity of ecosystems to provide services. The models are continuously developed to include an increasing number of processes and to utilize the growing amounts of observed data becoming available. However, while the versatility of the models is increasing as new processes and variables are added, their accuracy suffers from the accumulation of uncertainty, especially in the absence of overarching principles controlling their concerted behaviour. We have initiated a collaborative working group to address this problem based on a 'missing law' - adaptation and optimization principles rooted in natural selection. Even though this 'missing law' constrains relationships between traits, and therefore can vastly reduce the number of uncertain parameters in ecosystem models, it has rarely been applied to DGVMs. Our recent research have shown that optimization- and trait-based models of gross primary production can be both much simpler and more accurate than current models based on fixed functional types, and that observed plant carbon allocations and distributions of plant functional traits are predictable with eco-evolutionary models. While there are also many other examples of the usefulness of these and other theoretical principles, it is not always straight-forward to make them operational in predictive models. In particular on longer time scales, the representation of functional diversity and the dynamical interactions among individuals and species presents a formidable challenge. Here we will present recent ideas on the use of adaptation and optimization principles in vegetation models, including examples of promising developments, but also limitations of the principles and some key challenges.

  18. Hiro and Evans currents in Vertical Disruption Event

    NASA Astrophysics Data System (ADS)

    Zakharov, Leonid; Xujing Li Team; Sergei Galkin Team

    2014-10-01

    The notion of Tokamak Magneto-Hydrodynamics (TMHD), which explicitly reflects the anisotropy of a high temperature tokamak plasma is introduced. The set of TMHD equations is formulated for simulations of macroscopic plasma dynamics and disruptions in tokamaks. Free from the Courant restriction on the time step, this set of equations is appropriate for high performance plasmas and does not require any extension of the MHD plasma model. At the same time, TMHD requires the use of magnetic field aligned numerical grids. The TMHD model was used for creation of theory of the Wall Touching Kink and Vertical Modes (WTKM and WTVM), prediction of Hiro and Evans currents, design of an innovative diagnostics for Hiro current measurements, installed on EAST device. While Hiro currents have explained the toroidal asymmetry in the plasma current measurements in JET disruptions, the Evans currents explain the tile current measurements in tokamaks. The recently developed Vertical Disruption Code (VDE) have demonstrated 5 regimes of VDE and confirmed the generation of both Hiro and Evans currents. The results challenge the 24 years long misinterpretation of the tile currents in tokamaks as ``halo'' currents, which were a product of misuse of equilibrium reconstruction for VDE. This work is supported by US DoE Contract No. DE-AC02-09-CH1146.

  19. Damage prognosis: the future of structural health monitoring.

    PubMed

    Farrar, Charles R; Lieven, Nick A J

    2007-02-15

    This paper concludes the theme issue on structural health monitoring (SHM) by discussing the concept of damage prognosis (DP). DP attempts to forecast system performance by assessing the current damage state of the system (i.e. SHM), estimating the future loading environments for that system, and predicting through simulation and past experience the remaining useful life of the system. The successful development of a DP capability will require the further development and integration of many technology areas including both measurement/processing/telemetry hardware and a variety of deterministic and probabilistic predictive modelling capabilities, as well as the ability to quantify the uncertainty in these predictions. The multidisciplinary and challenging nature of the DP problem, its current embryonic state of development, and its tremendous potential for life-safety and economic benefits qualify DP as a 'grand challenge' problem for engineers in the twenty-first century.

  20. From the big bang to the brain.

    PubMed

    Boliek, C A; Lohmeier, H

    1999-01-01

    Current research on the capacities of the infant has lead to a better understanding of developmental processes underlying cognition and motor skill acquisition. ASHA's Eighth Annual Research Symposium on Infant-Toddler Development, in November 1998, included a presentation on developmental cognitive science by Dr. Andrew Meltzoff and a presentation on motor skill acquisition by Dr. Esther Thelen. The theoretical constructs and data presented served to broaden our current perspectives on infant abilities. The data reported by Meltzoff and Thelen challenged several long-standing theories of infant cognition and motor development. Alternative theoretical models were used to describe skill acquisition during the first several years of life. Our response will include a brief summary of each investigator's presentation, discuss their findings with respect to research in the area of infant speech physiology and production, and provide possible future directions and challenges for individuals conducting developmental research.

  1. Diet-Regulated Anxiety

    PubMed Central

    Murphy, Michelle; Mercer, Julian G.

    2013-01-01

    A substantial proportion of noncommunicable disease originates in habitual overconsumption of calories, which can lead to weight gain and obesity and attendant comorbidities. At the other end of the spectrum, the consequences of undernutrition in early life and at different stages of adult life can also have major impact on wellbeing and quality of life. To help address some of these issues, greater understanding is required of interactions with food and contemporary diets throughout the life course and at a number of different levels: physiological, metabolic, psychological, and emotional. Here we review the current literature on the effects of dietary manipulation on anxiety-like behaviour. This evidence, assembled from study of preclinical models of diet challenge from gestation to adult life, supports a role for diet in the important connections between psychology, physiology, and behaviour. Analogous processes in the human population in our current obesogenic environment are likely to contribute to individual and societal challenges in this area. PMID:24027581

  2. Rapid development of entity-based data models for bioinformatics with persistence object-oriented design and structured interfaces.

    PubMed

    Ezra Tsur, Elishai

    2017-01-01

    Databases are imperative for research in bioinformatics and computational biology. Current challenges in database design include data heterogeneity and context-dependent interconnections between data entities. These challenges drove the development of unified data interfaces and specialized databases. The curation of specialized databases is an ever-growing challenge due to the introduction of new data sources and the emergence of new relational connections between established datasets. Here, an open-source framework for the curation of specialized databases is proposed. The framework supports user-designed models of data encapsulation, objects persistency and structured interfaces to local and external data sources such as MalaCards, Biomodels and the National Centre for Biotechnology Information (NCBI) databases. The proposed framework was implemented using Java as the development environment, EclipseLink as the data persistency agent and Apache Derby as the database manager. Syntactic analysis was based on J3D, jsoup, Apache Commons and w3c.dom open libraries. Finally, a construction of a specialized database for aneurysms associated vascular diseases is demonstrated. This database contains 3-dimensional geometries of aneurysms, patient's clinical information, articles, biological models, related diseases and our recently published model of aneurysms' risk of rapture. Framework is available in: http://nbel-lab.com.

  3. Bioreactor Engineering of Stem Cell Environments

    PubMed Central

    Tandon, Nina; Marolt, Darja; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2013-01-01

    Stem cells hold promise to revolutionize modern medicine by development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to translation of stem cell based therapies into the clinic. PMID:23531529

  4. Joint trajectories of cognitive functioning and challenging behavior for persons living with dementia in long-term care.

    PubMed

    Robitaille, Annie; Garcia, Linda; McIntosh, Cameron

    2015-09-01

    The current study examines the longitudinal relationship between dementia-related challenging behaviors (e.g., vocal disruption, physical aggression, repetitive behaviors, and restlessness) and cognitive functioning in the long-term care (LTC) context. A multivariate latent growth curve model within the structural equation modeling (SEM) framework was applied to data collected from 16,804 older adults upon admission to LTC and every 3 months for a period of 2.5 years. Increases in challenging behaviors were characterized by a significant positive linear and negative quadratic trend (i.e., a subtle leveling off at later assessment times), whereas increases in cognitive impairment were characterized by a positive linear trend. On average, individuals who were more cognitively impaired upon entry into LTC and who exhibited a steeper increase in cognitive impairment also exhibited more challenging behaviors at entry into LTC and a steeper increase in challenging behaviors, respectively. At the within-person level, individuals demonstrating an increase in cognitive impairment at a specific occasion were also more likely to demonstrate an increase in challenging behaviors at that same occasion; however, the magnitude of these effects was very small, suggesting limited practical implications. This study provides novel empirical evidence about the coevolution of cognitive impairment and challenging behaviors, going beyond prior research that has been either cross-sectional in nature, examined longitudinal change in only 1 variable, or simply looked at linear trends without attempting to explore the possibility of nonlinear change. Most importantly, this longitudinal examination of persons with dementia living in LTC has implications for how challenging behaviors can be better managed and for how new strategies can be implemented to prevent challenging behaviors. (c) 2015 APA, all rights reserved).

  5. The SAMPL4 host-guest blind prediction challenge: an overview.

    PubMed

    Muddana, Hari S; Fenley, Andrew T; Mobley, David L; Gilson, Michael K

    2014-04-01

    Prospective validation of methods for computing binding affinities can help assess their predictive power and thus set reasonable expectations for their performance in drug design applications. Supramolecular host-guest systems are excellent model systems for testing such affinity prediction methods, because their small size and limited conformational flexibility, relative to proteins, allows higher throughput and better numerical convergence. The SAMPL4 prediction challenge therefore included a series of host-guest systems, based on two hosts, cucurbit[7]uril and octa-acid. Binding affinities in aqueous solution were measured experimentally for a total of 23 guest molecules. Participants submitted 35 sets of computational predictions for these host-guest systems, based on methods ranging from simple docking, to extensive free energy simulations, to quantum mechanical calculations. Over half of the predictions provided better correlations with experiment than two simple null models, but most methods underperformed the null models in terms of root mean squared error and linear regression slope. Interestingly, the overall performance across all SAMPL4 submissions was similar to that for the prior SAMPL3 host-guest challenge, although the experimentalists took steps to simplify the current challenge. While some methods performed fairly consistently across both hosts, no single approach emerged as consistent top performer, and the nonsystematic nature of the various submissions made it impossible to draw definitive conclusions regarding the best choices of energy models or sampling algorithms. Salt effects emerged as an issue in the calculation of absolute binding affinities of cucurbit[7]uril-guest systems, but were not expected to affect the relative affinities significantly. Useful directions for future rounds of the challenge might involve encouraging participants to carry out some calculations that replicate each others' studies, and to systematically explore parameter options.

  6. Leveraging organismal biology to forecast the effects of climate change.

    PubMed

    Buckley, Lauren B; Cannistra, Anthony F; John, Aji

    2018-04-26

    Despite the pressing need for accurate forecasts of ecological and evolutionary responses to environmental change, commonly used modelling approaches exhibit mixed performance because they omit many important aspects of how organisms respond to spatially and temporally variable environments. Integrating models based on organismal phenotypes at the physiological, performance and fitness levels can improve model performance. We summarize current limitations of environmental data and models and discuss potential remedies. The paper reviews emerging techniques for sensing environments at fine spatial and temporal scales, accounting for environmental extremes, and capturing how organisms experience the environment. Intertidal mussel data illustrate biologically important aspects of environmental variability. We then discuss key challenges in translating environmental conditions into organismal performance including accounting for the varied timescales of physiological processes, for responses to environmental fluctuations including the onset of stress and other thresholds, and for how environmental sensitivities vary across lifecycles. We call for the creation of phenotypic databases to parameterize forecasting models and advocate for improved sharing of model code and data for model testing. We conclude with challenges in organismal biology that must be solved to improve forecasts over the next decade.acclimation, biophysical models, ecological forecasting, extremes, microclimate, spatial and temporal variability.

  7. Implementing PAT with Standards

    NASA Astrophysics Data System (ADS)

    Chandramohan, Laakshmana Sabari; Doolla, Suryanarayana; Khaparde, S. A.

    2016-02-01

    Perform Achieve Trade (PAT) is a market-based incentive mechanism to promote energy efficiency. The purpose of this work is to address the challenges inherent to inconsistent representation of business processes, and interoperability issues in PAT like cap-and-trade mechanisms especially when scaled. Studies by various agencies have highlighted that as the mechanism evolves including more industrial sectors and industries in its ambit, implementation will become more challenging. This paper analyses the major needs of PAT (namely tracking, monitoring, auditing & verifying energy-saving reports, and providing technical support & guidance to stakeholders); and how the aforesaid reasons affect them. Though current technologies can handle these challenges to an extent, standardization activities for implementation have been scanty for PAT and this work attempts to evolve them. The inconsistent modification of business processes, rules, and procedures across stakeholders, and interoperability among heterogeneous systems are addressed. This paper proposes the adoption of specifically two standards into PAT, namely Business Process Model and Notation for maintaining consistency in business process modelling, and Common Information Model (IEC 61970, 61968, 62325 combined) for information exchange. Detailed architecture and organization of these adoptions are reported. The work can be used by PAT implementing agencies, stakeholders, and standardization bodies.

  8. Regulatory Disruption and Arbitrage in Health-Care Data Protection.

    PubMed

    Terry, Nicolas P

    This article explains how the structure of U.S. health-care data protection (specifically its sectoral and downstream properties) has led to a chronically uneven policy environment for different types of health-care data. It examines claims for health-care data protection exceptionalism and competing demands such as data liquidity. In conclusion, the article takes the position that healthcare- data exceptionalism remains a valid imperative and that even current concerns about data liquidity can be accommodated in an exceptional protective model. However, re-calibrating our protection of health-care data residing outside of the traditional health-care domain is challenging, currently even politically impossible. Notwithstanding, a hybrid model is envisioned with downstream HIPAA model remaining the dominant force within the health-care domain, but being supplemented by targeted upstream and point-of-use protections applying to health-care data in disrupted spaces.

  9. High-Energy Electron-Ion and Photon-Ion Collisions: Status and Challenges

    NASA Technical Reports Server (NTRS)

    Kallman, Timothy R.

    2010-01-01

    Non-LTE plasmas are ubiquitous in objects studied in the UV and X-ray energy bands. Collisional and photoionization cross sections for atoms and ions are fundamental to our ability to model such plasmas. Modeling is key in the X-ray band, where detector properties and limited spectral resolution limit the ability to measure model-independent line strengths, or other spectral features. Much of the motivation for studying such collisions and many of the tools, are not new. However, the motivation for such studies and their applications, have been affected by the advent of X-ray spectroscopy with the gratings on Chandra and XMM-Newton. In this talk I will review this motivation and describe the tools currently in use for such studies. I will also describe some current unresolved problems and the likely future needs for such data.

  10. Ocean-Science Mission Needs: Real-Time AUV Data for Command, Control, and Model Inputs

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.; Costello, D. K.; Warrior, H.; Langebrake, L. C.; Hou, W.; Patten, J. T.; Kaltenbacher, E.

    2001-01-01

    Predictive models for tides, hydrodynamics, and bio-optical properties affecting the visibility and buoyancy of coastal waters are needed to evaluate the safety of personnel and equipment engaged in maritime operations under potentially hazardous conditions. Predicted currents can be markedly different for two-layer systems affected by terrestrial runoff than for well-mixed conditions because the layering decouples the surface and bottom Ekman layers and rectifies the current response to oscillatory upwelling-and downwelling-favorable winds. Standard ocean models (e.g. Princeton Ocean Model) require initial-and boundary data on the physical and optical properties of the multilayered water column to provide accurate simulations of heat budgets and circulation. Two observational systems are designed to measure vertically structured conditions on the West Florida Shelf (WFS): a tethered buoy network and an autonomous underwater vehicle (AUV) observational system. The AUV system is described with a focus on the observational systems that challenge or limit the communications command and control network for various types of measurement programs. These include vertical oscillatory missions on shelf transects to observe the optical and hydrographic properties of the water column, and bottom-following missions for measuring the bottom albedo. Models of light propagation, absorption, and conversion to heat as well as determination of the buoyancy terms for physical models require these measurements. High data rates associated with video bottom imagery are the most challenging for the real-time, command and control communications system, but they are met through a combination of loss-less and lossy data-compression methods, depending upon the data-rate of the radio links.

  11. Smart health monitoring systems: an overview of design and modeling.

    PubMed

    Baig, Mirza Mansoor; Gholamhosseini, Hamid

    2013-04-01

    Health monitoring systems have rapidly evolved during the past two decades and have the potential to change the way health care is currently delivered. Although smart health monitoring systems automate patient monitoring tasks and, thereby improve the patient workflow management, their efficiency in clinical settings is still debatable. This paper presents a review of smart health monitoring systems and an overview of their design and modeling. Furthermore, a critical analysis of the efficiency, clinical acceptability, strategies and recommendations on improving current health monitoring systems will be presented. The main aim is to review current state of the art monitoring systems and to perform extensive and an in-depth analysis of the findings in the area of smart health monitoring systems. In order to achieve this, over fifty different monitoring systems have been selected, categorized, classified and compared. Finally, major advances in the system design level have been discussed, current issues facing health care providers, as well as the potential challenges to health monitoring field will be identified and compared to other similar systems.

  12. Bring It On, Complexity! Present and Future of Self-Organising Middle-Out Abstraction

    NASA Astrophysics Data System (ADS)

    Mammen, Sebastian Von; Steghöfer, Jan-Philipp

    The following sections are included: * The Great Complexity Challenge * Self-Organising Middle-Out Abstraction * Optimising Graphics, Physics and Artificial Intelligence * Emergence and Hierarchies in a Natural System * The Technical Concept of SOMO * Observation of interactions * Interaction pattern recognition and behavioural abstraction * Creating and adjusting hierarchies * Confidence measures * Execution model * Learning SOMO: parameters, knowledge propagation, and procreation * Current Implementations * Awareness Beyond Virtuality * Integration and emergence * Model inference * SOMO net * SOMO after me * The Future of SOMO

  13. The challenges of simulating wake vortex encounters and assessing separation criteria

    NASA Technical Reports Server (NTRS)

    Dunham, R. E.; Stuever, Robert A.; Vicroy, Dan D.

    1993-01-01

    During landings and take-offs, the longitudinal spacing between airplanes is in part determined by the safe separation required to avoid the trailing vortex wake of the preceding aircraft. Safe exploration of the feasibility of reducing longitudinal separation standards will require use of aircraft simulators. This paper discusses the approaches to vortex modeling, methods for modeling the aircraft/vortex interaction, some of the previous attempts of defining vortex hazard criteria, and current understanding of the development of vortex hazard criteria.

  14. A co-productive health leadership model to support the liberation of the NHS.

    PubMed

    Nicol, Edward; Sang, Bob

    2011-02-01

    Following the recent white paper - Equity and Excellence: Liberating the NHS - we need a 21st-century model of leadership in the NHS that re-focuses on the centrality of the relationship between clinicians and patients. This paper argues the case for co-productive 'Health Leadership' that can meet the challenges set by the current Big Society agenda, Darzi and Wanless, so that we achieve a sustainable, high quality NHS, fit for the 21st century.

  15. One dark matter mystery: halos in the cosmic web

    NASA Astrophysics Data System (ADS)

    Gaite, Jose

    2015-01-01

    The current cold dark matter cosmological model explains the large scale cosmic web structure but is challenged by the observation of a relatively smooth distribution of matter in galactic clusters. We consider various aspects of modeling the dark matter around galaxies as distributed in smooth halos and, especially, the smoothness of the dark matter halos seen in N-body cosmological simulations. We conclude that the problems of the cold dark matter cosmology on small scales are more serious than normally admitted.

  16. Composite annotations: requirements for mapping multiscale data and models to biomedical ontologies

    PubMed Central

    Cook, Daniel L.; Mejino, Jose L. V.; Neal, Maxwell L.; Gennari, John H.

    2009-01-01

    Current methods for annotating biomedical data resources rely on simple mappings between data elements and the contents of a variety of biomedical ontologies and controlled vocabularies. Here we point out that such simple mappings are inadequate for large-scale multiscale, multidomain integrative “virtual human” projects. For such integrative challenges, we describe a “composite annotation” schema that is simple yet sufficiently extensible for mapping the biomedical content of a variety of data sources and biosimulation models to available biomedical ontologies. PMID:19964601

  17. Inheriting Curiosity: Leveraging MBSE to Build Mars2020

    NASA Technical Reports Server (NTRS)

    Fosse, Elyse; Harmon, Corey; Lefland, Mallory; Castillo, Robert; Devereaux, Ann

    2015-01-01

    The success of the Jet Propulsion Laboratory's (JPL) Martian mission Mars Science Laboratory (MSL) prompted NASA to challenge JPL to build a second rover, Mars2020. Mars2020 has chosen to infuse Model Based Systems Engineering (MBSE) in pursuit of aiding the design of the Flight System. This paper will derive the motivation for MBSE infusion and will explain the current state of the Mars2020 Flight System Model. Successes in MBSE adoption will be discussed, as will limitations to the methodology.

  18. Spatial data standards meet meteorological data - pushing the boundaries

    NASA Astrophysics Data System (ADS)

    Wagemann, Julia; Siemen, Stephan; Lamy-Thepaut, Sylvie

    2017-04-01

    The data archive of the European Centre for Medium-Range Weather Forecasts (ECMWF) holds around 120 PB of data and is world's largest archive of meteorological data. This information is of great value for many Earth Science disciplines, but the complexity of the data (up to five dimensions and different time axis domains) and its native data format GRIB, while being an efficient archive format, limits the overall data uptake especially from users outside the MetOcean domain. ECMWF's MARS WebAPI is a very efficient and flexible system for expert users to access and retrieve meteorological data, though challenging for users outside the MetOcean domain. With the help of web-based standards for data access and processing, ECMWF wants to make more than 1 PB of meteorological and climate data easier accessible to users across different Earth Science disciplines. As climate data provider for the H2020 project EarthServer-2, ECMWF explores the feasibility to give on-demand access to it's MARS archive via the OGC standard interface Web Coverage Service (WCS). Despite the potential a WCS for climate and meteorological data offers, the standards-based modelling of meteorological and climate data entails many challenges and reveals the boundaries of the current Web Coverage Service 2.0 standard. Challenges range from valid semantic data models for meteorological data to optimal and efficient data structures for a scalable web service. The presentation reviews the applicability of the current Web Coverage Service 2.0 standard to meteorological and climate data and discusses challenges that are necessary to overcome in order to achieve real interoperability and to ensure the conformant sharing and exchange of meteorological data.

  19. Addressing educational challenges in veterinary medicine through the use of distance education.

    PubMed

    Murray, Amanda L; Sischo, William M

    2007-01-01

    The veterinary profession is currently facing many educational challenges, including an insufficient capacity to train and educate veterinarians for the multiple disciplines within the profession, a shortage of veterinarians in private and public practice, a shortage of faculty, a lack of human and professional diversity, and a rising cost of education resulting in extreme student debt loads. As a methodology for teaching, distance education (DE) has the potential to address many of these issues. By its very nature, DE can increase the capacity of current facilities and faculty. In addition, DE can allow students to acquire the necessary knowledge at less cost. This article describes a model for incorporating DE in the form of interactive Web-based courses, in conjunction with short, intensive residential programs, for the lecture portions of courses taught in the pre-veterinary, veterinary, and post-veterinary educational periods. In this model, the Web-based courses are used to convey the necessary core knowledge required at each step of the educational process. The residential portions are then used to apply the knowledge in such a way as to combine clinical applications with research in basic and applied sciences. Distance education can provide increased flexibility, high-quality educational experiences, and a less costly alternative for students while maximizing the reach of current faculty efforts and the capacity of existing physical structures.

  20. Man, mind, and machine: the past and future of virtual reality simulation in neurologic surgery.

    PubMed

    Robison, R Aaron; Liu, Charles Y; Apuzzo, Michael L J

    2011-11-01

    To review virtual reality in neurosurgery, including the history of simulation and virtual reality and some of the current implementations; to examine some of the technical challenges involved; and to propose a potential paradigm for the development of virtual reality in neurosurgery going forward. A search was made on PubMed using key words surgical simulation, virtual reality, haptics, collision detection, and volumetric modeling to assess the current status of virtual reality in neurosurgery. Based on previous results, investigators extrapolated the possible integration of existing efforts and potential future directions. Simulation has a rich history in surgical training, and there are numerous currently existing applications and systems that involve virtual reality. All existing applications are limited to specific task-oriented functions and typically sacrifice visual realism for real-time interactivity or vice versa, owing to numerous technical challenges in rendering a virtual space in real time, including graphic and tissue modeling, collision detection, and direction of the haptic interface. With ongoing technical advancements in computer hardware and graphic and physical rendering, incremental or modular development of a fully immersive, multipurpose virtual reality neurosurgical simulator is feasible. The use of virtual reality in neurosurgery is predicted to change the nature of neurosurgical education, and to play an increased role in surgical rehearsal and the continuing education and credentialing of surgical practitioners. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Integrating cultural humility into health care professional education and training.

    PubMed

    Chang, E-shien; Simon, Melissa; Dong, XinQi

    2012-05-01

    As US populations become increasing diverse, healthcare professionals are facing a heightened challenge to provide cross-cultural care. To date, medical education around the world has developed specific curricula on cultural competence training in acknowledgement of the importance of culturally sensitive and grounded services. This article proposes to move forward by integrating the concept of cultural humility into current trainings, in which we believe, is vital in complementing the current model, and better prepare future professionals to address health challenges with culturally appropriate care. Based on the works of Chinese philosophers, cultural values and the contemporary Chinese immigrants' experience, we hereby present the QIAN (Humbleness) curriculum: the importance of self-Questioning and critique, bi-directional cultural Immersion, mutually Active-listening, and the flexibility of Negotiation. The principles of the QIAN curriculum reside not only between the patient and the healthcare professional dyad, but also elicit the necessary support of family, health care system as well as the community at large. The QIAN curriculum could improve practice and enhance the exploration, comprehension and appreciation of the cultural orientations between healthcare professionals and patients which ultimately could improve patient satisfaction, patient-healthcare professional relationship, medical adherence and the reduction of health disparities. QIAN model is highly adaptable to other cultural and ethnic groups in multicultural societies around the globe. Incorporating its framework into the current medical education may enhance cross-cultural clinical encounters.

  2. Laser powder bed fusion additive manufacturing of metals; physics, computational, and materials challenges

    NASA Astrophysics Data System (ADS)

    King, W. E.; Anderson, A. T.; Ferencz, R. M.; Hodge, N. E.; Kamath, C.; Khairallah, S. A.; Rubenchik, A. M.

    2015-12-01

    The production of metal parts via laser powder bed fusion additive manufacturing is growing exponentially. However, the transition of this technology from production of prototypes to production of critical parts is hindered by a lack of confidence in the quality of the part. Confidence can be established via a fundamental understanding of the physics of the process. It is generally accepted that this understanding will be increasingly achieved through modeling and simulation. However, there are significant physics, computational, and materials challenges stemming from the broad range of length and time scales and temperature ranges associated with the process. In this paper, we review the current state of the art and describe the challenges that need to be met to achieve the desired fundamental understanding of the physics of the process.

  3. Efficacy of rabies immunoglobulins in an experimental post-exposure prophylaxis rodent model.

    PubMed

    Servat, Alexandre; Lutsch, Charles; Delore, Valentine; Lang, Jean; Veitch, Keith; Cliquet, Florence

    2003-12-12

    In a recently published Syrian hamster animal challenge study [Vaccine 19 (2001) 2273], a highly purified, heat-treated equine rabies immunoglobulin (pERIG HT, Favirab) did not elicit satisfactory protection. The efficacies of this batch, a second stage pERIG HT batch and reference RIG preparations (Imorab, Imogam Rage pasteurised, Berna antiserum) were compared in mice challenged with either Ariana canine field strain or CVS strain. Survival rates against Ariana challenge with the second pERIG HT batch were indistinguishable from those of other licensed preparations (83-90% survival), but the deficient batch did not provide satisfactory protection (53%). These data confirm the inadequate response to a first stage pERIG HT batch, but a current batch provides equivalent protection to that afforded by licensed HRIG and ERIG preparations.

  4. Personalized medicine: challenges and opportunities for translational bioinformatics

    PubMed Central

    Overby, Casey Lynnette; Tarczy-Hornoch, Peter

    2013-01-01

    Personalized medicine can be defined broadly as a model of healthcare that is predictive, personalized, preventive and participatory. Two US President’s Council of Advisors on Science and Technology reports illustrate challenges in personalized medicine (in a 2008 report) and in use of health information technology (in a 2010 report). Translational bioinformatics is a field that can help address these challenges and is defined by the American Medical Informatics Association as “the development of storage, analytic and interpretive methods to optimize the transformation of increasing voluminous biomedical data into proactive, predictive, preventative and participatory health.” This article discusses barriers to implementing genomics applications and current progress toward overcoming barriers, describes lessons learned from early experiences of institutions engaged in personalized medicine and provides example areas for translational bioinformatics research inquiry. PMID:24039624

  5. Can We Sustainably Harvest Ivory?

    PubMed

    Lusseau, David; Lee, Phyllis C

    2016-11-07

    Despite the 1989 ivory trade ban, elephants continue to be killed to harvest their tusks for ivory. Since 2008, this poaching has increased to unprecedented levels driven by consumer demand for ivory products. CITES is now considering the development of a legal ivory trade [1, 2]. The proposal relies on three assumptions: (1) harvest regulation will cease all illegal activities, (2) defined sustainable quotas can be enforced, and (3) we can define meaningful sustainable quotas that come close to the current demand. We know that regulation of harvest does not stop illegal takes. Despite whaling regulation after World War II, illegal whaling continued for decades [3]. The introduction of wolf culls in the US actually increased poaching activities [4], and one-off ivory sales in 1999 and 2008 did nothing to halt elephant poaching. Governance issues over the ivory supply chains, including stockpiling, make enforcing quotas challenging, if not impossible [5, 6]. We have not yet adequately assessed what could be a sustainable ivory yield. To do so, we develop a compartmental model composed of a two-sex age-structured demographic model and an ivory production and harvest model. We applied several offtake and quota strategies to define how much ivory could be sustainably harvested. We found that the sustainability space is very small. Only 100 to 150 kg of ivory could be removed from a reference population of 1,360 elephants, levels well below the current demand. Our study shows that lifting the ivory ban will not address the current poaching challenge. We should instead focus on reducing consumer demand. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Accelerating the Integration of Distributed Water Solutions: A Conceptual Financing Model from the Electricity Sector

    NASA Astrophysics Data System (ADS)

    Quesnel, Kimberly J.; Ajami, Newsha K.; Wyss, Noemi

    2017-11-01

    Modern challenges require new approaches to urban water management. One solution in the portfolio of potential strategies is the integration of distributed water infrastructure, practices, and technologies into existing systems. However, many practical barriers have prevented the widespread adoption of these systems in the US. The objective of this paper is to address these challenges by developing a conceptual model encompassing regulatory, financial, and governance components that can be used to incorporate new distributed water solutions into our current network. To construct the model, case studies of successfully implemented distributed electricity systems, specifically energy efficiency and renewable energy technologies, were examined to determine how these solutions have become prominent in recent years and what lessons can be applied to the water sector in a similar pursuit. The proposed model includes four action-oriented elements: catalyzing change, establishing funding sources, using resource pathways, and creating innovative governance structures. As illustrated in the model, the water sector should use suite of coordinated policies to promote change, engage end users through fiscal incentives, and encourage research, development and dissemination of new technologies over time.

  7. Simulation Modeling for Off-Nominal Conditions - Where Are We Today?

    NASA Technical Reports Server (NTRS)

    Shah, Gautam H.; Foster, John V.; Cunningham, Kevin

    2010-01-01

    The modeling of aircraft flight characteris4cs in off-nominal or otherwise adverse conditions has become increasingly important for simulation in the loss-of-control arena. Adverse conditions include environmentally-induced upsets such as wind shear or wake vortex encounters; off-nominal flight conditions, such as stall or departure; on-board systems failures; and structural failures or aircraft damage. Spirited discussions in the research community are taking place as to the fidelity and data requirements for adequate representation of vehicle dynamics under such conditions for a host of research areas, including recovery training, flight controls development, trajectory guidance/planning, and envelope limiting. The increasing need for multiple sources of data (empirical, computational, experimental) for modeling across a larger flight envelope leads to challenges in developing methods of appropriately applying or combining such data, particularly in a dynamic flight environment with a physically and/or aerodynamically asymmetric vehicle. Traditional simplifications and symmetry assumptions in current modeling methodology may no longer be valid. Furthermore, once modeled, challenges abound in the validation of flight dynamics characteristics in adverse flight regimes

  8. Accelerating the Integration of Distributed Water Solutions: A Conceptual Financing Model from the Electricity Sector.

    PubMed

    Quesnel, Kimberly J; Ajami, Newsha K; Wyss, Noemi

    2017-11-01

    Modern challenges require new approaches to urban water management. One solution in the portfolio of potential strategies is the integration of distributed water infrastructure, practices, and technologies into existing systems. However, many practical barriers have prevented the widespread adoption of these systems in the US. The objective of this paper is to address these challenges by developing a conceptual model encompassing regulatory, financial, and governance components that can be used to incorporate new distributed water solutions into our current network. To construct the model, case studies of successfully implemented distributed electricity systems, specifically energy efficiency and renewable energy technologies, were examined to determine how these solutions have become prominent in recent years and what lessons can be applied to the water sector in a similar pursuit. The proposed model includes four action-oriented elements: catalyzing change, establishing funding sources, using resource pathways, and creating innovative governance structures. As illustrated in the model, the water sector should use suite of coordinated policies to promote change, engage end users through fiscal incentives, and encourage research, development and dissemination of new technologies over time.

  9. Evaluation of Current Planetary Boundary Layer Retrieval Capabilities from Space

    NASA Technical Reports Server (NTRS)

    Santanello, Joseph A., Jr.; Schaefer, Alexander J.; Blaisdell, John; Yorks, John

    2016-01-01

    The PBL over land remains a significant gap in our water and energy cycle understanding from space. This work combines unique NASA satellite and model products to demonstrate the ability of current sensors (advanced IR sounding and lidar) to retrieve PBL properties and in turn their potential to be used globally to evaluate and improve weather and climate prediction models. While incremental progress has been made in recent AIRS retrieval versions, insufficient vertical resolution remains in terms of detecting PBL properties. Lidar shows promise in terms of detecting vertical gradients (and PBLh) in the lower troposphere, but daytime conditions over land remain a challenge due to noise, and their coverage is limited to approximately 2 weeks or longer return times.

  10. Futility Disputes: A Review of the Literature and Proposed Model for Dispute Navigation Through Trust Building.

    PubMed

    Leland, Brian D; Torke, Alexia M; Wocial, Lucia D; Helft, Paul R

    2017-10-01

    Futility disputes in the intensive care unit setting have received significant attention in the literature over the past several years. Although the idea of improving communication in an attempt to resolve these challenging situations has been regularly discussed, the concept and role of trust building as the means by which communication improves and disputes are best navigated is largely absent. We take this opportunity to review the current literature on futility disputes and argue the important role of broken trust in these encounters, highlighting current evidence establishing the necessity and utility of trust in both medical decision-making and effective communication. Finally, we propose a futility dispute navigation model built upon improved communication through trust building.

  11. The Challenge of Human Spermatozoa Proteome: A Systematic Review.

    PubMed

    Gilany, Kambiz; Minai-Tehrani, Arash; Amini, Mehdi; Agharezaee, Niloofar; Arjmand, Babak

    2017-01-01

    Currently, there are 20,197 human protein-coding genes in the most expertly curated database (UniProtKB/Swiss-Pro). Big efforts have been made by the international consortium, the Chromosome-Centric Human Proteome Project (C-HPP) and independent researchers, to map human proteome. In brief, anno 2017 the human proteome was outlined. The male factor contributes to 50% of infertility in couples. However, there are limited human spermatozoa proteomic studies. Firstly, the development of the mapping of the human spermatozoa was analyzed. The human spermatozoa have been used as a model for missing proteins. It has been shown that human spermatozoa are excellent sources for finding missing proteins. Y chromosome proteome mapping is led by Iran. However, it seems that it is extremely challenging to map the human spermatozoa Y chromosome proteins based on current mass spectrometry-based proteomics technology. Post-translation modifications (PTMs) of human spermatozoa proteome are the most unexplored area and currently the exact role of PTMs in male infertility is unknown. Additionally, the clinical human spermatozoa proteomic analysis, anno 2017 was done in this study.

  12. Osteotomy models - the current status on pain scoring and management in small rodents.

    PubMed

    Lang, Annemarie; Schulz, Anja; Ellinghaus, Agnes; Schmidt-Bleek, Katharina

    2016-12-01

    Fracture healing is a complex regeneration process which produces new bone tissue without scar formation. However, fracture healing disorders occur in approximately 10% of human patients and cause severe pain and reduced quality of life. Recently, the development of more standardized, sophisticated and commercially available osteosynthesis techniques reflecting clinical approaches has increased the use of small rodents such as rats and mice in bone healing research dramatically. Nevertheless, there is no standard for pain assessment, especially in these species, and consequently limited information regarding the welfare aspects of osteotomy models. Moreover, the selection of analgesics is restricted for osteotomy models since non-steroidal anti-inflammatory drugs (NSAIDs) are known to affect the initial, inflammatory phase of bone healing. Therefore, opioids such as buprenorphine and tramadol are often used. However, dosage data in the literature are varied. Within this review, we clarify the background of osteotomy models, explain the current status and challenges of animal welfare assessment, and provide an example score sheet including model specific parameters. Furthermore, we summarize current refinement options and present a brief outlook on further 3R research. © The Author(s) 2016.

  13. Additive Manufacturing Modeling and Simulation A Literature Review for Electron Beam Free Form Fabrication

    NASA Technical Reports Server (NTRS)

    Seufzer, William J.

    2014-01-01

    Additive manufacturing is coming into industrial use and has several desirable attributes. Control of the deposition remains a complex challenge, and so this literature review was initiated to capture current modeling efforts in the field of additive manufacturing. This paper summarizes about 10 years of modeling and simulation related to both welding and additive manufacturing. The goals were to learn who is doing what in modeling and simulation, to summarize various approaches taken to create models, and to identify research gaps. Later sections in the report summarize implications for closed-loop-control of the process, implications for local research efforts, and implications for local modeling efforts.

  14. A systems thinking approach to analysis of the Patient Protection and Affordable Care Act.

    PubMed

    Williams, John C

    2015-01-01

    The public health community is challenged with understanding the many complexities presented by systems thinking and its applications in systems modeling. The model presented encompasses multiple variables needed (eg, model building) for the construction of a conceptual system model of the Patient Protection and Affordable Care Act (ACA). The model tracks the ACA from inception, through passage, March 2010, to its current state. Justification for the need to reform the current health care system rests, in part, on the heels of social justice. Proponents of the ACA have long argued that health reform was needed by the millions of uninsured person who suffered from health disparities, took little advantage of health prevention advice, and faced issues of access to providers as well as insurers. In addition the ACA seeks to address our uncontrollable spending on health care delivery. This article highlights the ACA from a systems perspective. The conceptual model presented encompasses both health reform variables (eg, health care provisions, key legislative components, system environment) and system variables (eg, inputs, outputs, feedback, and throughput) needed to understand current health care reform efforts from a systems perspective. The model presented shows how the interrelationships and interconnections of elements of a system come together to achieve its purpose or goal.

  15. Modelling the urban water cycle as an integrated part of the city: a review.

    PubMed

    Urich, Christian; Rauch, Wolfgang

    2014-01-01

    In contrast to common perceptions, the urban water infrastructure system is a complex and dynamic system that is constantly evolving and adapting to changes in the urban environment, to sustain existing services and provide additional ones. Instead of simplifying urban water infrastructure to a static system that is decoupled from its urban context, new management strategies use the complexity of the system to their advantage by integrating centralised with decentralised solutions and explicitly embedding water systems into their urban form. However, to understand and test possible adaptation strategies, urban water modelling tools are required to support exploration of their effectiveness as the human-technology-environment system coevolves under different future scenarios. The urban water modelling community has taken first steps to developing these new modelling tools. This paper critically reviews the historical development of urban water modelling tools and provides a summary of the current state of integrated modelling approaches. It reflects on the challenges that arise through the current practice of coupling urban water management tools with urban development models and discusses a potential pathway towards a new generation of modelling tools.

  16. Dendritic trafficking faces physiologically critical speed-precision tradeoffs

    PubMed Central

    Williams, Alex H; O'Donnell, Cian; Sejnowski, Terrence J; O'Leary, Timothy

    2016-01-01

    Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons. DOI: http://dx.doi.org/10.7554/eLife.20556.001 PMID:28034367

  17. Implantation, removal and replacement of subretinal electronic implants for restoration of vision in patients with retinitis pigmentosa.

    PubMed

    Gekeler, Katrin; Bartz-Schmidt, Karl Ulrich; Sachs, Helmut; MacLaren, Robert E; Stingl, Katarina; Zrenner, Eberhart; Gekeler, Florian

    2018-05-01

    The purpose of this review is to provide an update on the efforts to restore vision through subretinal implants in patients with degenerative retinal diseases. In addition to the current technique and its latest improvements, it will focus on the surgical technique of implantation as well as explantation and reimplantation. The durability of the current subretinal implant RETINA IMPLANT Alpha AMS has increased substantially compared with the predecessor model RETINA IMPLANT Alpha IMS. According to validated examinations in the laboratory, a median lifetime of 4.7 years will be reached in clinical use; in similar examinations, the previous model has reached only 8 months. Visual function has slightly increased. The surgical technique for subretinal implants is complex and demanding for ophthalmic surgeons, as it is multifaceted and combines novel surgical steps in areas, which are not commonly entered such as the suprachoroidal and the subretinal space. The surgical approach for implantation has matured considerably and has led to successful implantation in 64 patient cases. Surgical challenges are now mainly encountered with the exact subfoveal positioning of the device. The explantation procedure is relatively straight-forward because the implant can be withdrawn in a reverse direction along the already existent subretinal path. Reimplantations, however, are more challenging because some degree of scar tissue may exist along the path of the chip and around the scleral trapdoor. Nevertheless, reimplantations have now been carried out successfully in four patients. The new RETINA IMPLANT Alpha AMS shows significantly improved durability compared with the predecessor model RETINA IMPLANT Alpha IMS. The subretinal implant offers excellent visual results but requires experienced surgeons. Explantation of devices is straight-forward, and reimplantations are challenging but have been successful in four patients.

  18. Quantitative and qualitative synthesis of socio-hydrological research

    NASA Astrophysics Data System (ADS)

    Xu, L.; Gober, P.; Wheater, H. S.; Kajikawa, Y.

    2017-12-01

    The challenge of climate change adaptation has raised awareness of the feedbacks and interconnections in complex human-natural coupled water systems. This has reinforced the call for a socio-hydrological approach to better understand, and represent in models, the associated system dynamics. Such models can potentially provide the tools to link knowledge about complex water systems to decision-making and policy frameworks. Socio-hydrology, as the subfield of human-natural coupled systems analysis, has been dramatically developed in the past few years. The purpose of this study is to empirically examine work that has been framed under the umbrella of socio-hydrology, to provide insights into the participants and their disciplinary perspectives, and to draw conclusions about where the field is headed. In doing so, we used a combined quantitative and qualitative approach to synthesise current knowledge of socio-hydrology and to propose some promising future directions in this subfield of water sciences. The general statistics of the existing literature showed that socio-hydrological research has become an emerging topic and is drawing more concern and engagement of hydrologists. However, the participation of social scientists is inadequate and greater cross-disciplinary integration is desirable. Current concerns in this subfield of water research centre on two basic challenges: (1) the need to embrace the social dimensions of water-related risks, and (2) the importance of interactions and feedbacks in dynamic socio-hydrological systems. A third challenge identified here relates to the large-scale implications of 1) and 2) above, i.e. virtual water flows as a mechanism to track the human use of water at the global scale. Accordingly, we propose five potential directions with regard to socio-hydrological models, interdisciplinary collaboration and transdisciplinary studies, the science-policy interface, resilience in socio-hydrological systems, and data sharing for human-water system studies.

  19. Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

    PubMed

    Wilczynski, Bartek; Furlong, Eileen E M

    2010-04-15

    Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  20. Detection and quantification of flow consistency in business process models.

    PubMed

    Burattin, Andrea; Bernstein, Vered; Neurauter, Manuel; Soffer, Pnina; Weber, Barbara

    2018-01-01

    Business process models abstract complex business processes by representing them as graphical models. Their layout, as determined by the modeler, may have an effect when these models are used. However, this effect is currently not fully understood. In order to systematically study this effect, a basic set of measurable key visual features is proposed, depicting the layout properties that are meaningful to the human user. The aim of this research is thus twofold: first, to empirically identify key visual features of business process models which are perceived as meaningful to the user and second, to show how such features can be quantified into computational metrics, which are applicable to business process models. We focus on one particular feature, consistency of flow direction, and show the challenges that arise when transforming it into a precise metric. We propose three different metrics addressing these challenges, each following a different view of flow consistency. We then report the results of an empirical evaluation, which indicates which metric is more effective in predicting the human perception of this feature. Moreover, two other automatic evaluations describing the performance and the computational capabilities of our metrics are reported as well.

  1. Developing Generic Competences in the European Higher Education Area: A Proposal for Teaching the Principles of Economics

    ERIC Educational Resources Information Center

    Velasco, Manuel Salas; Sanchez Martinez, Maria Teresa; Ferrero, Noelina Rodriguez

    2012-01-01

    The participation of Spain in the European Higher Education Area (EHEA) involves a number of important challenges for academics. Adapting to an educational model that is characterised by competence-based teaching is a difficult task, yet it is of paramount importance in the context of current reforms. In an educational system in which the…

  2. An effective assessment protocol for continuous geospatial datasets of forest characteristics using USFS Forest Inventory and Analysis (FIA) data

    Treesearch

    Rachel Riemann; Barry Tyler Wilson; Andrew Lister; Sarah Parks

    2010-01-01

    Geospatial datasets of forest characteristics are modeled representations of real populations on the ground. The continuous spatial character of such datasets provides an incredible source of information at the landscape level for ecosystem research, policy analysis, and planning applications, all of which are critical for addressing current challenges related to...

  3. A perspective on laboratory utilization management from Canada.

    PubMed

    Naugler, Christopher

    2014-01-01

    Utilization, particularly in chemistry and molecular testing, is growing rapidly in Canada at a time when laboratory budgets are shrinking. Canadian laboratories face particular challenges as the prevailing funding model limits the scope for new revenue generation. Aggressive and coordinated interventions to reduce over-utilization will be necessary to ensure the long-term viability of the current system. © 2013.

  4. Dialogic Action in Climate Change Discussions: An International Study of High School Students in China, New Zealand, Norway and the United States

    ERIC Educational Resources Information Center

    Arya, Diana J.; Parker, Jessica K.

    2015-01-01

    Global efforts to prepare young developing minds for solving current and future challenges of climate change have advocated interdisciplinary, issues-based instructional approaches in order to transform traditional models of science education as delivering conceptual facts (UNESCO, 2014). This study is an exploration of the online interactions in…

  5. Putting the "Team" in the Fine Arts Team: An Application of Business Management Team Concepts

    ERIC Educational Resources Information Center

    Fisher, Ryan

    2007-01-01

    In this article, the author discusses current challenges to the idea of teamwork in fine arts teams, redefines the terms team and collaboration using a business management perspective, discusses the success of effective teams in the business world and the characteristics of those teams, and proposes the implementation of the business model of…

  6. The Effect of an Adaptive Online Learning Support in an Undergraduate Computer Course: An Exploration of Self-Regulation in Blended Contexts

    ERIC Educational Resources Information Center

    Ko, Chia-Yin

    2013-01-01

    In accordance with Zimmerman's self-regulated learning model, the proposed online learning tool in the current study was designed to support students in learning a challenging subject. The Self-Check List, Formative Self-Assessment, and Structured Online Discussion served goal-setting, self-monitoring, and self-reflective purposes. The…

  7. A percent-level determination of the nucleon axial coupling from Quantum Chromodynamics

    DOE PAGES

    Chang, Chia C.; Rinaldi, Enrico; Nicholson, A. N.; ...

    2018-06-15

    Here, the axial coupling of the nucleon, g A, is the strength of its coupling to the weak axial current of the Standard Model, much as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates, for example, the rate of β-decay of neutrons to protons and the strength of the attractive long-range force between nucleons. Precision tests of the Standard Model in nuclear environments require a quantitative understanding of nuclear physics rooted in Quantum Chromodynamics, a pillar of this theory. The prominence of g A makes it a benchmark quantity to determinemore » from theory, a difficult task as the theory is non-perturbative. Lattice QCD provides a rigorous, non-perturbative definition of the theory which can be numerically implemented. In order to determine g A, the lattice QCD community has identified two challenges that must be overcome to achieve a 2% precision by 2020: the excited state contamination must be controlled, and the statistical precision must be markedly improved. Here we report a calculation of g A QCD =1.271 ± 0.013, using an unconventional method11 that overcomes these challenges.« less

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mahesh, M; Borras, C; Frey, G

    This workshop is jointly organized by the AAPM, the Spanish (SEFM) and the Russian (AMPR) Medical Physics Societies, as part of formal educational exchange agreements signed by the AAPM with each one of these two societies.With the rapid technological advances in radiation therapy both for treatment and imaging, it is challenging how physics is taught to medical physicists practicing in radiation therapy. The main Objectives: of this workshop is to bring forth current status, challenges and issues related to education of radiation therapy physicists here in the US, Spain and Russia. Medical physicists from each one of these countries willmore » present educational requirements of international recommendations and directives and analyze their impact on national legislations. Current and future educational models and plans for harmonization will be described. The role of universities, professional societies and examination boards, such as the American Board of Radiology, will be discussed. Minimum standards will be agreed upon. Learning Objectives: Review medical physics educational models supported by AAPM, SEFM, and AMPR. Discuss the role of governmental and non-governmental organizations in elaborating and adopting medical physics syllabi. Debate minimum educational standards for medical physics education based on country-specific resources.« less

  9. A percent-level determination of the nucleon axial coupling from Quantum Chromodynamics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Chia C.; Rinaldi, Enrico; Nicholson, A. N.

    Here, the axial coupling of the nucleon, g A, is the strength of its coupling to the weak axial current of the Standard Model, much as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates, for example, the rate of β-decay of neutrons to protons and the strength of the attractive long-range force between nucleons. Precision tests of the Standard Model in nuclear environments require a quantitative understanding of nuclear physics rooted in Quantum Chromodynamics, a pillar of this theory. The prominence of g A makes it a benchmark quantity to determinemore » from theory, a difficult task as the theory is non-perturbative. Lattice QCD provides a rigorous, non-perturbative definition of the theory which can be numerically implemented. In order to determine g A, the lattice QCD community has identified two challenges that must be overcome to achieve a 2% precision by 2020: the excited state contamination must be controlled, and the statistical precision must be markedly improved. Here we report a calculation of g A QCD =1.271 ± 0.013, using an unconventional method11 that overcomes these challenges.« less

  10. Homeland security: sharing and managing critical incident information

    NASA Astrophysics Data System (ADS)

    Ashley, W. R., III

    2003-09-01

    Effective critical incident response for homeland security requires access to real-time information from many organizations. Command and control, as well as basic situational awareness, are all dependant on quickly communicating a dynamically changing picture to a variety of decision makers. For the most part, critical information management is not unfamiliar or new to the public safety community. However, new challenges present themselves when that information needs to be seamlessly shared across multiple organizations at the local, state and federal level in real-time. The homeland security problem does not lend itself to the traditional military joint forces planning model where activities shift from a deliberate planning process to a crisis action planning process. Rather, the homeland security problem is more similar to a traditional public safety model where the current activity state moves from complete inactivity or low-level attention to immediate crisis action planning. More often than not the escalation occurs with no warning or baseline information. This paper addresses the challenges of sharing critical incident information and the impacts new technologies will have on this problem. The value of current and proposed approaches will be critiqued for operational value and areas will be identified for further development.

  11. Effective connectivity: Influence, causality and biophysical modeling

    PubMed Central

    Valdes-Sosa, Pedro A.; Roebroeck, Alard; Daunizeau, Jean; Friston, Karl

    2011-01-01

    This is the final paper in a Comments and Controversies series dedicated to “The identification of interacting networks in the brain using fMRI: Model selection, causality and deconvolution”. We argue that discovering effective connectivity depends critically on state-space models with biophysically informed observation and state equations. These models have to be endowed with priors on unknown parameters and afford checks for model Identifiability. We consider the similarities and differences among Dynamic Causal Modeling, Granger Causal Modeling and other approaches. We establish links between past and current statistical causal modeling, in terms of Bayesian dependency graphs and Wiener–Akaike–Granger–Schweder influence measures. We show that some of the challenges faced in this field have promising solutions and speculate on future developments. PMID:21477655

  12. Translational research and the evolving landscape for biomedical innovation.

    PubMed

    Kaitin, Kenneth I

    2012-10-01

    This article addresses current challenges facing pharmaceutical and biopharmaceutical developers, including the expiration of patents on many high-revenue-generating products, increasing competition in the marketplace, low public support, high regulatory hurdles, and the increasing time, cost, and risk of new product development. To meet these challenges, drug developers are looking to new models of innovation to improve efficiency, lower risk, and increase output. These new models include codevelopment agreements with small companies, multicompany consortia, and strategic partnerships with academic research centers. In the United States and the European Union, the government is supporting these efforts by creating incentives for academic centers to foster translational research and become more "commercially minded". The goal for all stakeholders is to reduce the barriers to product development and bring new medicines to market in a timely and cost-efficient manner.

  13. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models

    PubMed Central

    Watson, Alan M.; Klimstra, William B.

    2017-01-01

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus. PMID:28398253

  14. Challenges in Timeseries Analysis from Microlensing

    NASA Astrophysics Data System (ADS)

    Street, R. A.

    2017-06-01

    Despite a flood of discoveries over the last ~ 20 years, our knowledge of the exoplanet population is incomplete owing to a gap between the sensitivities of different detection techniques. However, a census of exoplanets at all separations from their host stars is essential to fully understand planet formation mechanisms. Microlensing offers an effective way to bridge the gap around 1-10 AU and is therefore one of the major science goals of the Wide Field Infrared Survey Telescope (WFIRST) mission. WFIRST's survey of the Galactic Bulge is expected to discover ~ 20,000 microlensing events, including ~ 3000 planets, which represents a substantial data analysis challenge with the modeling software currently available. This paper highlights areas where further work is needed. The community is encouraged to join new software development efforts aimed at making the modeling of microlensing events both more accessible and rigorous.

  15. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.

    PubMed

    Watson, Alan M; Klimstra, William B

    2017-04-11

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus.

  16. Towards Current Profile Control in ITER: Potential Approaches and Research Needs

    NASA Astrophysics Data System (ADS)

    Schuster, E.; Barton, J. E.; Wehner, W. P.

    2014-10-01

    Many challenging plasma control problems still need to be addressed in order for the ITER Plasma Control System (PCS) to be able to successfully achieve the ITER project goals. For instance, setting up a suitable toroidal current density profile is key for one possible advanced scenario characterized by noninductive sustainment of the plasma current and steady-state operation. The nonlinearity and high dimensionality exhibited by the plasma demand a model-based current-profile control synthesis procedure that can accommodate this complexity through embedding the known physics within the design. The development of a model capturing the dynamics of the plasma relevant for control design enables not only the design of feedback controllers for regulation or tracking but also the design of optimal feedforward controllers for a systematic model-based approach to scenario planning, the design of state estimators for a reliable real-time reconstruction of the plasma internal profiles based on limited and noisy diagnostics, and the development of a fast predictive simulation code for closed-loop performance evaluation before implementation. Progress towards control-oriented modeling of the current profile evolution and associated control design has been reported following both data-driven and first-principles-driven approaches. An overview of these two approaches will be provided, as well as a discussion on research needs associated with each one of the model applications described above. Supported by the US Department of Energy under DE-SC0001334 and DE-SC0010661.

  17. Magnetospheric Substorm Evolution in the Magnetotail: Challenge to Global MHD Modeling.

    NASA Astrophysics Data System (ADS)

    Kuznetsova, M. M.; Hesse, M.; Dorelli, J.; Rastaetter, L.

    2003-12-01

    Testing the ability of global MHD models to describe magnetotail evolution during substroms is one of the elements of science based validation efforts at CCMC. We perform simulations of magnetotail dynamics using global MHD models residing at CCMC. We select solar wind conditions which drive the accumulation of magnetic field in the tail lobes and subsequent magnetic reconnection and energy release. We will analyze the effects of spatial resolution in the plasma sheet on modeled expansion phase evolution, maximum energy stored in the tail, and details of magnetotail reconnection. We will pay special attention to current sheet thinning and multiple plasmoid formation.

  18. A complex systems approach to constructing better models for managing financial markets and the economy

    NASA Astrophysics Data System (ADS)

    Farmer, J. Doyne; Gallegati, M.; Hommes, C.; Kirman, A.; Ormerod, P.; Cincotti, S.; Sanchez, A.; Helbing, D.

    2012-11-01

    We outline a vision for an ambitious program to understand the economy and financial markets as a complex evolving system of coupled networks of interacting agents. This is a completely different vision from that currently used in most economic models. This view implies new challenges and opportunities for policy and managing economic crises. The dynamics of such models inherently involve sudden and sometimes dramatic changes of state. Further, the tools and approaches we use emphasize the analysis of crises rather than of calm periods. In this they respond directly to the calls of Governors Bernanke and Trichet for new approaches to macroeconomic modelling.

  19. Predictive risk models for proximal aortic surgery

    PubMed Central

    Díaz, Rocío; Pascual, Isaac; Álvarez, Rubén; Alperi, Alberto; Rozado, Jose; Morales, Carlos; Silva, Jacobo; Morís, César

    2017-01-01

    Predictive risk models help improve decision making, information to our patients and quality control comparing results between surgeons and between institutions. The use of these models promotes competitiveness and led to increasingly better results. All these virtues are of utmost importance when the surgical operation entails high-risk. Although proximal aortic surgery is less frequent than other cardiac surgery operations, this procedure itself is more challenging and technically demanding than other common cardiac surgery techniques. The aim of this study is to review the current status of predictive risk models for patients who undergo proximal aortic surgery, which means aortic root replacement, supracoronary ascending aortic replacement or aortic arch surgery. PMID:28616348

  20. In vivo imaging in NHP models of malaria: challenges, progress and outlooks.

    PubMed

    Beignon, Anne-Sophie; Le Grand, Roger; Chapon, Catherine

    2014-02-01

    Animal models of malaria, mainly mice, have made a large contribution to our knowledge of host-pathogen interactions and immune responses, and to drug and vaccine design. Non-human primate (NHP) models for malaria are admittedly under-used, although they are probably closer models than mice for human malaria; in particular, NHP models allow the use of human pathogens (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi). NHPs, whether natural hosts or experimentally challenged with a simian Plasmodium, can also serve as robust pre-clinical models. Some simian parasites are closely related to a human counterpart, with which they may share a common ancestor, and display similar major features with the human infection and pathology. NHP models allow longitudinal studies, from the early events following sporozoite inoculation to the later events, including analysis of organs and tissues, particularly liver, spleen, brain and bone marrow. NHP models have one other significant advantage over mouse models: NHPs are our closest relatives and thus their biology is very similar to ours. Recently developed in vivo imaging tools have provided insight into malaria parasite infection and disease in mouse models. One advantage of these tools is that they limit the need for invasive procedures, such as tissue biopsies. Many such technologies are now available for NHP studies and provide new opportunities for elucidating host/parasite interactions. The aim of this review is to bring the malaria community up to date on what is currently possible and what soon will be, in terms of in vivo imaging in NHP models of malaria, to consider the pros and the cons of the various techniques, and to identify challenges. © 2013.

  1. CEDAR Electrodynamics Thermosphere Ionosphere (ETI) Challenge for Systematic Assessment of Ionosphere/Thermosphere Models: NmF2, hmF2, and Vertical Drift Using Ground-Based Observations

    NASA Technical Reports Server (NTRS)

    Shim, J. S.; Kuznetsova, M.; Rastatter, L.; Hesse, M.; Bilitza, D.; Butala, M.; Codrescu, M.; Emery, B.; Foster, B.; Fuller-Rowell, T.; hide

    2011-01-01

    Objective quantification of model performance based on metrics helps us evaluate the current state of space physics modeling capability, address differences among various modeling approaches, and track model improvements over time. The Coupling, Energetics, and Dynamics of Atmospheric Regions (CEDAR) Electrodynamics Thermosphere Ionosphere (ETI) Challenge was initiated in 2009 to assess accuracy of various ionosphere/thermosphere models in reproducing ionosphere and thermosphere parameters. A total of nine events and five physical parameters were selected to compare between model outputs and observations. The nine events included two strong and one moderate geomagnetic storm events from GEM Challenge events and three moderate storms and three quiet periods from the first half of the International Polar Year (IPY) campaign, which lasted for 2 years, from March 2007 to March 2009. The five physical parameters selected were NmF2 and hmF2 from ISRs and LEO satellites such as CHAMP and COSMIC, vertical drifts at Jicamarca, and electron and neutral densities along the track of the CHAMP satellite. For this study, four different metrics and up to 10 models were used. In this paper, we focus on preliminary results of the study using ground-based measurements, which include NmF2 and hmF2 from Incoherent Scatter Radars (ISRs), and vertical drifts at Jicamarca. The results show that the model performance strongly depends on the type of metrics used, and thus no model is ranked top for all used metrics. The analysis further indicates that performance of the model also varies with latitude and geomagnetic activity level.

  2. Modelling DC responses of 3D complex fracture networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beskardes, Gungor Didem; Weiss, Chester Joseph

    Here, the determination of the geometrical properties of fractures plays a critical role in many engineering problems to assess the current hydrological and mechanical states of geological media and to predict their future states. However, numerical modeling of geoelectrical responses in realistic fractured media has been challenging due to the explosive computational cost imposed by the explicit discretizations of fractures at multiple length scales, which often brings about a tradeoff between computational efficiency and geologic realism. Here, we use the hierarchical finite element method to model electrostatic response of realistically complex 3D conductive fracture networks with minimal computational cost.

  3. Modelling DC responses of 3D complex fracture networks

    DOE PAGES

    Beskardes, Gungor Didem; Weiss, Chester Joseph

    2018-03-01

    Here, the determination of the geometrical properties of fractures plays a critical role in many engineering problems to assess the current hydrological and mechanical states of geological media and to predict their future states. However, numerical modeling of geoelectrical responses in realistic fractured media has been challenging due to the explosive computational cost imposed by the explicit discretizations of fractures at multiple length scales, which often brings about a tradeoff between computational efficiency and geologic realism. Here, we use the hierarchical finite element method to model electrostatic response of realistically complex 3D conductive fracture networks with minimal computational cost.

  4. Therapeutic Genome Editing: Prospects and Challenges

    PubMed Central

    Cox, David Benjamin Turitz; Platt, Randall Jeffrey; Zhang, Feng

    2015-01-01

    Recent advances in the development of genome editing technologies based on programmable nucleases have significantly improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress towards developing programmable nuclease-based therapies as well as future prospects and challenges. PMID:25654603

  5. Why is the VLT Very Efficient?

    NASA Astrophysics Data System (ADS)

    Comerón, F.

    2009-09-01

    The operations model of the ESO Very Large Telescope (VLT) heavily relies on a full-scale implementation of Service Mode observing. In this contribution we review the main features of ESO's approach to Service Mode at the VLT, we outline the advantages offered by this mode, and the challenges faced when implementing it given the wide diversity of instrumentation and instrument modes currently available at the VLT and the VLT Interferometer (VLTI). We give special emphasis to the part of this challenge directly derived from the evolution of the atmospheric conditions, which drive the short-term scheduling of the different scientific programmes competing for the available time.

  6. Preclinical evaluation of bacterially produced RSV-G protein vaccine: Strong protection against RSV challenge in cotton rat model

    PubMed Central

    Fuentes, Sandra; Klenow, Laura; Golding, Hana; Khurana, Surender

    2017-01-01

    In current study, we evaluated the safety and protective efficacy of recombinant unglycosylated RSV G protein ectodomain produced in E. coli (in presence and absence of oil-in-water adjuvant) in a preclinical RSV susceptible cotton rat challenge model compared to formaldehyde inactivated RSV (FI-RSV) and live RSV experimental infection. The adjuvanted G protein vaccine induced robust neutralization antibody responses comparable to those generated by live RSV infection. Importantly, adjuvanted G protein significantly reduced viral loads in both the lungs and nose at early time points following viral challenge. Antibody kinetics determined by Surface Plasmon Resonance showed that adjuvanted G generated 10-fold higher G-binding antibodies compared to non-adjvuanted G vaccine and live RSV infection, which correlated strongly with both neutralization titers and viral load titers in the nose and lungs post-viral challenge. Antibody diversity analysis revealed immunodominant antigenic sites in the N- and C-termini of the RSV-G protein, that were boosted >10-fold by adjuvant and inversely correlated with viral load titers. Enhanced lung pathology was observed only in animals vaccinated with FI-RSV, but not in animals vaccinated with unadjuvanted or adjuvanted RSV-G vaccine after viral challenge. The bacterially produced unglycosylated G protein could be developed as a protective vaccine against RSV disease. PMID:28186208

  7. Web tools for predictive toxicology model building.

    PubMed

    Jeliazkova, Nina

    2012-07-01

    The development and use of web tools in chemistry has accumulated more than 15 years of history already. Powered by the advances in the Internet technologies, the current generation of web systems are starting to expand into areas, traditional for desktop applications. The web platforms integrate data storage, cheminformatics and data analysis tools. The ease of use and the collaborative potential of the web is compelling, despite the challenges. The topic of this review is a set of recently published web tools that facilitate predictive toxicology model building. The focus is on software platforms, offering web access to chemical structure-based methods, although some of the frameworks could also provide bioinformatics or hybrid data analysis functionalities. A number of historical and current developments are cited. In order to provide comparable assessment, the following characteristics are considered: support for workflows, descriptor calculations, visualization, modeling algorithms, data management and data sharing capabilities, availability of GUI or programmatic access and implementation details. The success of the Web is largely due to its highly decentralized, yet sufficiently interoperable model for information access. The expected future convergence between cheminformatics and bioinformatics databases provides new challenges toward management and analysis of large data sets. The web tools in predictive toxicology will likely continue to evolve toward the right mix of flexibility, performance, scalability, interoperability, sets of unique features offered, friendly user interfaces, programmatic access for advanced users, platform independence, results reproducibility, curation and crowdsourcing utilities, collaborative sharing and secure access.

  8. Electroencephalography (EEG) forward modeling via H(div) finite element sources with focal interpolation.

    PubMed

    Pursiainen, S; Vorwerk, J; Wolters, C H

    2016-12-21

    The goal of this study is to develop focal, accurate and robust finite element method (FEM) based approaches which can predict the electric potential on the surface of the computational domain given its structure and internal primary source current distribution. While conducting an EEG evaluation, the placement of source currents to the geometrically complex grey matter compartment is a challenging but necessary task to avoid forward errors attributable to tissue conductivity jumps. Here, this task is approached via a mathematically rigorous formulation, in which the current field is modeled via divergence conforming H(div) basis functions. Both linear and quadratic functions are used while the potential field is discretized via the standard linear Lagrangian (nodal) basis. The resulting model includes dipolar sources which are interpolated into a random set of positions and orientations utilizing two alternative approaches: the position based optimization (PBO) and the mean position/orientation (MPO) method. These results demonstrate that the present dipolar approach can reach or even surpass, at least in some respects, the accuracy of two classical reference methods, the partial integration (PI) and St. Venant (SV) approach which utilize monopolar loads instead of dipolar currents.

  9. Unifying concept of serotonin transporter-associated currents.

    PubMed

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

    2012-01-02

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

  10. Unifying Concept of Serotonin Transporter-associated Currents*

    PubMed Central

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

    2012-01-01

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents. PMID:22072712

  11. Mapping Base Modifications in DNA by Transverse-Current Sequencing

    NASA Astrophysics Data System (ADS)

    Alvarez, Jose R.; Skachkov, Dmitry; Massey, Steven E.; Kalitsov, Alan; Velev, Julian P.

    2018-02-01

    Sequencing DNA modifications and lesions, such as methylation of cytosine and oxidation of guanine, is even more important and challenging than sequencing the genome itself. The traditional methods for detecting DNA modifications are either insensitive to these modifications or require additional processing steps to identify a particular type of modification. Transverse-current sequencing in nanopores can potentially identify the canonical bases and base modifications in the same run. In this work, we demonstrate that the most common DNA epigenetic modifications and lesions can be detected with any predefined accuracy based on their tunneling current signature. Our results are based on simulations of the nanopore tunneling current through DNA molecules, calculated using nonequilibrium electron-transport methodology within an effective multiorbital model derived from first-principles calculations, followed by a base-calling algorithm accounting for neighbor current-current correlations. This methodology can be integrated with existing experimental techniques to improve base-calling fidelity.

  12. Eddy current analysis of cracks grown from surface defects and non-metallic particles

    NASA Astrophysics Data System (ADS)

    Cherry, Matthew R.; Hutson, Alisha; Aldrin, John C.; Shank, Jared

    2018-04-01

    Eddy current methods are sensitive to any discrete change in conductivity. Traditionally this has been used to determine the presence of a crack. However, other features that are not cracks such as non-metallic inclusions, carbide stringers and surface voids can cause an eddy current indication that could potentially lead to a reject of an in-service component. These features may not actually be lifelimiting, meaning NDE methods could reject components with remaining useful life. In-depth analysis of signals from eddy current sensors could provide a means of sorting between rejectable indications and false-calls from geometric and non-conductive features. In this project, cracks were grown from voids and non-metallic inclusions in a nickel-based super-alloy and eddy current analysis was performed on multiple intermediate steps of fatigue. Data were collected with multiple different ECT probes and at multiple frequencies, and the results were analyzed. The results show how cracks growing from non-metallic features can skew eddy current signals and make characterization a challenge. Modeling and simulation was performed with multiple analysis codes, and the models were found to be in good agreement with the data for cracks growing away from voids and non-metallic inclusions.

  13. Cloud Ice: A Climate Model Challenge With Signs and Expectations of Progress

    NASA Astrophysics Data System (ADS)

    Li, F.; Waliser, D.; Bacmeister, J.; Chern, J.; Del Genio, T.; Jiang, J.; Kharitondov, M.; Liou, K.; Meng, H.; Minnis, P.; Rossow, B.; Stephens, G.; Sun-Mack, S.; Tao, W.; Vane, D.; Woods, C.; Tompkins, A.; Wu, D.

    2007-12-01

    Global climate models (GCMs), including those assessed in the IPCC AR4, exhibit considerable disagreement in the amount of cloud ice - both in terms of the annual global mean as well as their spatial variability. Global measurements of cloud ice have been difficult due to the challenges involved in remotely sensing ice water content (IWC) and its vertical profile - including complications associated with multi-level clouds, mixed-phases and multiple hydrometer types, the uncertainty in classifying ice particle size and shape for remote retrievals, and the relatively small time and space scales associated with deep convection. Together, these measurement difficulties make it a challenge to characterize and understand the mechanisms of ice cloud formation and dissipation. Fortunately, there are new observational resources recently established that can be expected to lead to considerable reduction in the observational uncertainties of cloud ice, and in turn improve the fidelity of model representations. Specifically, these include the Microwave Limb Sounder (MLS) on the Earth Observing System (EOS) Aura satellite, and the CloudSat and Calipso satellite missions, all of which fly in formation in what is referred to as the A-Train. Based on radar and limb-sounding techniques, these new satellite measurements provide a considerable leap forward in terms of the information gathered regarding upper-tropospheric cloud IWC as well as other macrophysical and microphysical properties. In this presentation, we describe the current state of GCM representations of cloud ice and their associated uncertainties, the nature of the new observational resources for constraining cloud ice values in GCMs, the challenges in making model-data comparisons with these data resources, and prospects for near-term improvements in model representations.

  14. Coupled Atmosphere-Wave-Ocean Modeling of Tropical Cyclones: Progress, Challenges, and Ways Forward

    NASA Astrophysics Data System (ADS)

    Chen, Shuyi

    2015-04-01

    It has long been recognized that air-sea interaction plays an important role in tropical cyclones (TC) intensity change. However, most current numerical weather prediction (NWP) models are deficient in predicting TC intensity. The extreme high winds, intense rainfall, large ocean waves, and copious sea spray in TCs push the surface-exchange parameters for temperature, water vapor, and momentum into untested regimes. Parameterizations of air-sea fluxes in NWP models are often crude and create "manmade" energy source/sink that does not exist, especially in the absence of a fully interactive ocean in the model. The erroneous surface heat, moisture, and momentum fluxes can cause compounding errors in the model (e.g., precipitation, water vapor, boundary layer properties). The energy source (heat and moisture fluxes from the ocean) and sink (surface friction and wind-induced upper ocean cooling) are critical to TC intensity. However, observations of air-sea fluxes in TCs are very limited, especially in extreme high wind conditions underneath of the eyewall region. The Coupled Boundary Layer Air-Sea Transfer (CBLAST) program was designed to better understand the air-sea interaction, especially in high wind conditions, which included laboratory and coupled model experiments and field campaign in 2003-04 hurricane seasons. Significant progress has been made in better understanding of air-sea exchange coefficients up to 30 m/s, i.e., a leveling off in drag coefficient and relatively invariant exchange coefficient of enthalpy with wind speed. More recently, the Impact of Typhoon on the Ocean in the Pacific (ITOP) field campaign in 2010 has provided an unprecedented data set to study the air-sea fluxes in TCs and their impact on TC structure and intensity. More than 800 GPS dropsondes and 900 AXBTs/AXCTs as well as drifters, floats, and moorings were deployed in TCs, including Typhoons Fanapi and Malakas, and Supertyphoon Megi with a record peak wind speed of more than 80 m/s. It is found that the air-sea fluxes are quite asymmetric around a storm with complex features representing various air-sea interaction processes in TCs. A unique observation in Typhoon Fanapi is the development of a stable boundary layer in the near-storm cold wake region, which has a direct impact on TC inner core structure and intensity. Despite of the progress, challenges remain. Air-sea momentum exchange in wind speed greater than 30-40 m/s is largely unresolved. Directional wind-wave stress and wave-current stress are difficult to determine from observations. Effects of sea spray on the air-sea fluxes are still not well understood. This talk will provide an overview on progress made in recent years, challenges we are facing, and ways forward. An integrated coupled observational and atmosphere-wave-ocean modeling system is urgently needed, in which coupled model development and targeted observations from field campaign and lab measurements together form the core of the research and prediction system. Another important aspect is that fully coupled models provide explicit, integrated impact forecasts of wind, rain, waves, ocean currents and surges in TCs and winter storms, which are missing in most current NWP models. It requires a new strategy for model development, evaluation, and verification. Ensemble forecasts using high-resolution coupled atmosphere-wave-ocean models can provide probabilistic forecasts and quantitative uncertainty estimates, which also allow us to explore new methodologies to verify probabilistic impact forecasts and evaluate model physics using a stochastic approach. Examples of such approach in TCs including Superstorm Sandy will be presented.

  15. Opportunities and challenges of current electrophysiology research: a plea to establish 'translational electrophysiology' curricula.

    PubMed

    Lau, Dennis H; Volders, Paul G A; Kohl, Peter; Prinzen, Frits W; Zaza, Antonio; Kääb, Stefan; Oto, Ali; Schotten, Ulrich

    2015-05-01

    Cardiac electrophysiology has evolved into an important subspecialty in cardiovascular medicine. This is in part due to the significant advances made in our understanding and treatment of heart rhythm disorders following more than a century of scientific discoveries and research. More recently, the rapid development of technology in cellular electrophysiology, molecular biology, genetics, computer modelling, and imaging have led to the exponential growth of knowledge in basic cardiac electrophysiology. The paradigm of evidence-based medicine has led to a more comprehensive decision-making process and most likely to improved outcomes in many patients. However, implementing relevant basic research knowledge in a system of evidence-based medicine appears to be challenging. Furthermore, the current economic climate and the restricted nature of research funding call for improved efficiency of translation from basic discoveries to healthcare delivery. Here, we aim to (i) appraise the broad challenges of translational research in cardiac electrophysiology, (ii) highlight the need for improved strategies in the training of translational electrophysiologists, and (iii) discuss steps towards building a favourable translational research environment and culture. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  16. Multi -omics and metabolic modelling pipelines: challenges and tools for systems microbiology.

    PubMed

    Fondi, Marco; Liò, Pietro

    2015-02-01

    Integrated -omics approaches are quickly spreading across microbiology research labs, leading to (i) the possibility of detecting previously hidden features of microbial cells like multi-scale spatial organization and (ii) tracing molecular components across multiple cellular functional states. This promises to reduce the knowledge gap between genotype and phenotype and poses new challenges for computational microbiologists. We underline how the capability to unravel the complexity of microbial life will strongly depend on the integration of the huge and diverse amount of information that can be derived today from -omics experiments. In this work, we present opportunities and challenges of multi -omics data integration in current systems biology pipelines. We here discuss which layers of biological information are important for biotechnological and clinical purposes, with a special focus on bacterial metabolism and modelling procedures. A general review of the most recent computational tools for performing large-scale datasets integration is also presented, together with a possible framework to guide the design of systems biology experiments by microbiologists. Copyright © 2015. Published by Elsevier GmbH.

  17. Work-related Mental Health Surveillance in Brazil: characteristics, difficulties, and challenges.

    PubMed

    Araújo, Tania Maria; Palma, Tarciso de Figueiredo; Araújo, Natália do Carmo

    2017-10-01

    This paper addresses the challenges and difficulties in Work-related Mental Health (WMH) Surveillance in Brazil, based on a review of the bibliographic literature. From the compilation of identified academic research, it seeks to foster reflections about the current landscape of surveillance actions, its main obstacles, and possibilities for improvement. A survey of national publications was carried out using Scielo, Lilacs and PUBMED databases from 2002 until 2017. Systematizing the results allows us to group the following themes: Epidemiology of WMH in Brazil; Policies for WMH and VISAT; Work Environment for Mental Health; and, Actions and Interventions in the VISAT and WMH. The surveillance actions are still in the early stages; however, there is an effort to strengthen the RENAST, materialized in the creation of protocols and the promotion of national meetings which reflect the construction of a new surveillance model for worker health. We noted a search for new conceptual models of mental illness, a redefinition of the focus of care, and of intervention approaches highlighting the active role of workers, who are essential players in facing the challenges in this area.

  18. Design and validation of diffusion MRI models of white matter

    NASA Astrophysics Data System (ADS)

    Jelescu, Ileana O.; Budde, Matthew D.

    2017-11-01

    Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus.

  19. Current advancements and challenges in soil-root interactions modelling

    NASA Astrophysics Data System (ADS)

    Schnepf, Andrea; Huber, Katrin; Abesha, Betiglu; Meunier, Felicien; Leitner, Daniel; Roose, Tiina; Javaux, Mathieu; Vanderborght, Jan; Vereecken, Harry

    2015-04-01

    Roots change their surrounding soil chemically, physically and biologically. This includes changes in soil moisture and solute concentration, the exudation of organic substances into the rhizosphere, increased growth of soil microorganisms, or changes in soil structure. The fate of water and solutes in the root zone is highly determined by these root-soil interactions. Mathematical models of soil-root systems in combination with non-invasive techniques able to characterize root systems are a promising tool to understand and predict the behaviour of water and solutes in the root zone. With respect to different fields of applications, predictive mathematical models can contribute to the solution of optimal control problems in plant recourse efficiency. This may result in significant gains in productivity, efficiency and environmental sustainability in various land use activities. Major challenges include the coupling of model parameters of the relevant processes with the surrounding environment such as temperature, nutrient concentration or soil water content. A further challenge is the mathematical description of the different spatial and temporal scales involved. This includes in particular the branched structures formed by root systems or the external mycelium of mycorrhizal fungi. Here, reducing complexity as well as bridging between spatial scales is required. Furthermore, the combination of experimental and mathematical techniques may advance the field enormously. Here, the use of root system, soil and rhizosphere models is presented through a number of modelling case studies, including image based modelling of phosphate uptake by a root with hairs, model-based optimization of root architecture for phosphate uptake from soil, upscaling of rhizosphere models, modelling root growth in structured soil, and the effect of root hydraulic architecture on plant water uptake efficiency and drought resistance.

  20. Why we need better predictive models of vegetation phenology

    NASA Astrophysics Data System (ADS)

    Richardson, Andrew; Migliavacca, Mirco; Keenan, Trevor

    2014-05-01

    Vegetation phenology is strongly affected by climate change, with warmer temperatures causing earlier spring onset and delayed autumn senescence in most temperate and boreal ecosystems. In arid regions where phenology is driven by the seasonality of soil water availability, shifts in the timing, intensity, and total amount of precipitation are, likewise, affecting the seasonality of vegetation activity. Changes in the duration of the growing season have important implications for ecosystem productivity and uptake of CO2 from the atmosphere, as well as site water balance and runoff, microclimate, ecological interactions within and across trophic levels, and numerous feedbacks to the climate system associated with the surface energy budget. However, an outstanding challenge is that existing phenology sub-models used in ecosystem, land surface, and terrestrial biosphere models fail to adequately represent the seasonality, or sensitivity to environmental drivers, of vegetation phenology. This has two implications. First, these models are therefore likely to perform poorly under future climate scenarios. Second, the seasonality of important ecological processes and interactions, as well as biosphere-atmosphere feedbacks, is likely to be misrepresented as a result. Using data from several recent analyses, and focusing on temperate and boreal ecosystems, we will review current challenges associated with modeling vegetation phenology. We will discuss uncertainties associated with phenology model structure, model parameters, and driver sensitivity (forcing, chilling, and photoperiod). We will show why being able to extrapolate and generalize models (and model parameterization) is essential. We will consider added challenges associated with trying to model autumn phenology. Finally, we will use canopy photosynthesis and uptake of CO2 as an example of why improved understanding of the "rhythm of the seasons" is critically important.

  1. Design and validation of diffusion MRI models of white matter

    PubMed Central

    Jelescu, Ileana O.; Budde, Matthew D.

    2018-01-01

    Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus. PMID:29755979

  2. Current Advancements and Challenges in Soil-Root Interactions Modelling

    NASA Astrophysics Data System (ADS)

    Schnepf, A.; Huber, K.; Abesha, B.; Meunier, F.; Leitner, D.; Roose, T.; Javaux, M.; Vanderborght, J.; Vereecken, H.

    2014-12-01

    Roots change their surrounding soil chemically, physically and biologically. This includes changes in soil moisture and solute concentration, the exudation of organic substances into the rhizosphere, increased growth of soil microorganisms, or changes in soil structure. The fate of water and solutes in the root zone is highly determined by these root-soil interactions. Mathematical models of soil-root systems in combination with non-invasive techniques able to characterize root systems are a promising tool to understand and predict the behaviour of water and solutes in the root zone. With respect to different fields of applications, predictive mathematical models can contribute to the solution of optimal control problems in plant recourse efficiency. This may result in significant gains in productivity, efficiency and environmental sustainability in various land use activities. Major challenges include the coupling of model parameters of the relevant processes with the surrounding environment such as temperature, nutrient concentration or soil water content. A further challenge is the mathematical description of the different spatial and temporal scales involved. This includes in particular the branched structures formed by root systems or the external mycelium of mycorrhizal fungi. Here, reducing complexity as well as bridging between spatial scales is required. Furthermore, the combination of experimental and mathematical techniques may advance the field enormously. Here, the use of root system, soil and rhizosphere models is presented through a number of modelling case studies, including image based modelling of phosphate uptake by a root with hairs, model-based optimization of root architecture for phosphate uptake from soil, upscaling of rhizosphere models, modelling root growth in structured soil, and the effect of root hydraulic architecture on plant water uptake efficiency and drought resistance.

  3. Permanent human occupation of the central Tibetan Plateau in the early Holocene.

    PubMed

    Meyer, M C; Aldenderfer, M S; Wang, Z; Hoffmann, D L; Dahl, J A; Degering, D; Haas, W R; Schlütz, F

    2017-01-06

    Current models of the peopling of the higher-elevation zones of the Tibetan Plateau postulate that permanent occupation could only have been facilitated by an agricultural lifeway at ~3.6 thousand calibrated carbon-14 years before present. Here we report a reanalysis of the chronology of the Chusang site, located on the central Tibetan Plateau at an elevation of ~4270 meters above sea level. The minimum age of the site is fixed at ~7.4 thousand years (thorium-230/uranium dating), with a maximum age between ~8.20 and 12.67 thousand calibrated carbon-14 years before present (carbon-14 assays). Travel cost modeling and archaeological data suggest that the site was part of an annual, permanent, preagricultural occupation of the central plateau. These findings challenge current models of the occupation of the Tibetan Plateau. Copyright © 2017, American Association for the Advancement of Science.

  4. Developments in the Gung Ho dynamical core

    NASA Astrophysics Data System (ADS)

    Melvin, Thomas

    2017-04-01

    Gung Ho is the new dynamical core being developed for the next generation Met Office weather and climate model, suitable for meeting the exascale challenge on emerging computer architectures. It builds upon the earlier collaborative project between the Met Office, NERC and STFC Daresbury of the same name to investigate suitable numerical methods for dynamical cores. A mixed-finite element approach is used, where different finite element spaces are used to represent various fields. This method provides a number of beneficial improvements over the current model, such a compatibility and inherent conservation on quasi-uniform unstructured meshes, whilst maintaining the accuracy and good dispersion properties of the staggered grid currently used. Furthermore, the mixed finite element approach allows a large degree of flexibility in the type of mesh, order of approximation and discretisation, providing a simple way to test alternative options to obtain the best model possible.

  5. Coupled Data Assimilation for Integrated Earth System Analysis and Prediction: Goals, Challenges, and Recommendations

    NASA Technical Reports Server (NTRS)

    Penny, Stephen G.; Akella, Santha; Buehner, Mark; Chevallier, Matthieu; Counillon, Francois; Draper, Clara; Frolov, Sergey; Fujii, Yosuke; Karspeck, Alicia; Kumar, Arun

    2017-01-01

    The purpose of this report is to identify fundamental issues for coupled data assimilation (CDA), such as gaps in science and limitations in forecasting systems, in order to provide guidance to the World Meteorological Organization (WMO) on how to facilitate more rapid progress internationally. Coupled Earth system modeling provides the opportunity to extend skillful atmospheric forecasts beyond the traditional two-week barrier by extracting skill from low-frequency state components such as the land, ocean, and sea ice. More generally, coupled models are needed to support seamless prediction systems that span timescales from weather, subseasonal to seasonal (S2S), multiyear, and decadal. Therefore, initialization methods are needed for coupled Earth system models, either applied to each individual component (called Weakly Coupled Data Assimilation - WCDA) or applied the coupled Earth system model as a whole (called Strongly Coupled Data Assimilation - SCDA). Using CDA, in which model forecasts and potentially the state estimation are performed jointly, each model domain benefits from observations in other domains either directly using error covariance information known at the time of the analysis (SCDA), or indirectly through flux interactions at the model boundaries (WCDA). Because the non-atmospheric domains are generally under-observed compared to the atmosphere, CDA provides a significant advantage over single-domain analyses. Next, we provide a synopsis of goals, challenges, and recommendations to advance CDA: Goals: (a) Extend predictive skill beyond the current capability of NWP (e.g. as demonstrated by improving forecast skill scores), (b) produce physically consistent initial conditions for coupled numerical prediction systems and reanalyses (including consistent fluxes at the domain interfaces), (c) make best use of existing observations by allowing observations from each domain to influence and improve the full earth system analysis, (d) develop a robust observation-based identification and understanding of mechanisms that determine the variability of weather and climate, (e) identify critical weaknesses in coupled models and the earth observing system, (f) generate full-field estimates of unobserved or sparsely observed variables, (g) improve the estimation of the external forcings causing changes to climate, (h) transition successes from idealized CDA experiments to real-world applications. Challenges: (a) Modeling at the interfaces between interacting components of coupled Earth system models may be inadequate for estimating uncertainty or error covariances between domains, (b) current data assimilation methods may be insufficient to simultaneously analyze domains containing multiple spatiotemporal scales of interest, (c) there is no standardization of observation data or their delivery systems across domains, (d) the size and complexity of many large-scale coupled Earth system models makes it is difficult to accurately represent uncertainty due to model parameters and coupling parameters, (e) model errors lead to local biases that can transfer between the different Earth system components and lead to coupled model biases and long-term model drift, (e) information propagation across model components with different spatiotemporal scales is extremely complicated, and must be improved in current coupled modeling frameworks, (h) there is insufficient knowledge on how to represent evolving errors in non-atmospheric model components (e.g. as sea ice, land and ocean) on the timescales of NWP.

  6. Strategies for carbohydrate model building, refinement and validation

    PubMed Central

    2017-01-01

    Sugars are the most stereochemically intricate family of biomolecules and present substantial challenges to anyone trying to understand their nomenclature, reactions or branched structures. Current crystallographic programs provide an abstraction layer allowing inexpert structural biologists to build complete protein or nucleic acid model components automatically either from scratch or with little manual intervention. This is, however, still not generally true for sugars. The need for carbohydrate-specific building and validation tools has been highlighted a number of times in the past, concomitantly with the introduction of a new generation of experimental methods that have been ramping up the production of protein–sugar complexes and glycoproteins for the past decade. While some incipient advances have been made to address these demands, correctly modelling and refining carbohydrates remains a challenge. This article will address many of the typical difficulties that a structural biologist may face when dealing with carbohydrates, with an emphasis on problem solving in the resolution range where X-ray crystallography and cryo-electron microscopy are expected to overlap in the next decade. PMID:28177313

  7. The tell-tale look: viewing time, preferences, and prices.

    PubMed

    Gunia, Brian C; Murnighan, J Keith

    2015-01-01

    Even the simplest choices can prompt decision-makers to balance their preferences against other, more pragmatic considerations like price. Thus, discerning people's preferences from their decisions creates theoretical, empirical, and practical challenges. The current paper addresses these challenges by highlighting some specific circumstances in which the amount of time that people spend examining potential purchase items (i.e., viewing time) can in fact reveal their preferences. Our model builds from the gazing literature, in a purchasing context, to propose that the informational value of viewing time depends on prices. Consistent with the model's predictions, four studies show that when prices are absent or moderate, viewing time provides a signal that is consistent with a person's preferences and purchase intentions. When prices are extreme or consistent with a person's preferences, however, viewing time is a less reliable predictor of either. Thus, our model highlights a price-contingent "viewing bias," shedding theoretical, empirical, and practical light on the psychology of preferences and visual attention, and identifying a readily observable signal of preference.

  8. Unified selective sorting approach to analyse multi-electrode extracellular data

    NASA Astrophysics Data System (ADS)

    Veerabhadrappa, R.; Lim, C. P.; Nguyen, T. T.; Berk, M.; Tye, S. J.; Monaghan, P.; Nahavandi, S.; Bhatti, A.

    2016-06-01

    Extracellular data analysis has become a quintessential method for understanding the neurophysiological responses to stimuli. This demands stringent techniques owing to the complicated nature of the recording environment. In this paper, we highlight the challenges in extracellular multi-electrode recording and data analysis as well as the limitations pertaining to some of the currently employed methodologies. To address some of the challenges, we present a unified algorithm in the form of selective sorting. Selective sorting is modelled around hypothesized generative model, which addresses the natural phenomena of spikes triggered by an intricate neuronal population. The algorithm incorporates Cepstrum of Bispectrum, ad hoc clustering algorithms, wavelet transforms, least square and correlation concepts which strategically tailors a sequence to characterize and form distinctive clusters. Additionally, we demonstrate the influence of noise modelled wavelets to sort overlapping spikes. The algorithm is evaluated using both raw and synthesized data sets with different levels of complexity and the performances are tabulated for comparison using widely accepted qualitative and quantitative indicators.

  9. Unified selective sorting approach to analyse multi-electrode extracellular data

    PubMed Central

    Veerabhadrappa, R.; Lim, C. P.; Nguyen, T. T.; Berk, M.; Tye, S. J.; Monaghan, P.; Nahavandi, S.; Bhatti, A.

    2016-01-01

    Extracellular data analysis has become a quintessential method for understanding the neurophysiological responses to stimuli. This demands stringent techniques owing to the complicated nature of the recording environment. In this paper, we highlight the challenges in extracellular multi-electrode recording and data analysis as well as the limitations pertaining to some of the currently employed methodologies. To address some of the challenges, we present a unified algorithm in the form of selective sorting. Selective sorting is modelled around hypothesized generative model, which addresses the natural phenomena of spikes triggered by an intricate neuronal population. The algorithm incorporates Cepstrum of Bispectrum, ad hoc clustering algorithms, wavelet transforms, least square and correlation concepts which strategically tailors a sequence to characterize and form distinctive clusters. Additionally, we demonstrate the influence of noise modelled wavelets to sort overlapping spikes. The algorithm is evaluated using both raw and synthesized data sets with different levels of complexity and the performances are tabulated for comparison using widely accepted qualitative and quantitative indicators. PMID:27339770

  10. Thinking like an expert: surgical decision making as a cyclical process of being aware.

    PubMed

    Cristancho, Sayra M; Apramian, Tavis; Vanstone, Meredith; Lingard, Lorelei; Ott, Michael; Forbes, Thomas; Novick, Richard

    2016-01-01

    Education researchers are studying the practices of high-stake professionals as they learn how to better train for flexibility under uncertainty. This study explores the "Reconciliation Cycle" as the core element of an intraoperative decision-making model of how experienced surgeons assess and respond to challenges. We analyzed 32 semistructured interviews using constructivist grounded theory to develop a model of intraoperative decision making. Using constant comparison analysis, we built on this model with 9 follow-up interviews about the most challenging cases described in our dataset. The Reconciliation Cycle constituted an iterative process of "gaining" and "transforming information." The cyclical nature of surgeons' decision making suggested that transforming information requires a higher degree of awareness, not yet accounted by current conceptualizations of situation awareness. This study advances the notion of situation awareness in surgery. This characterization will support further investigations on how expert and nonexpert surgeons implement strategies to cope with unexpected events. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Shifting foundations: the mechanical cell wall and development.

    PubMed

    Braybrook, Siobhan A; Jönsson, Henrik

    2016-02-01

    The cell wall has long been acknowledged as an important physical mediator of growth in plants. Recent experimental and modelling work has brought the importance of cell wall mechanics into the forefront again. These data have challenged existing dogmas that relate cell wall structure to cell/organ growth, that uncouple elasticity from extensibility, and those which treat the cell wall as a passive and non-stressed material. Within this review we describe experiments and models which have changed the ways in which we view the mechanical cell wall, leading to new hypotheses and research avenues. It has become increasingly apparent that while we often wish to simplify our systems, we now require more complex multi-scale experiments and models in order to gain further insight into growth mechanics. We are currently experiencing an exciting and challenging shift in the foundations of our understanding of cell wall mechanics in growth and development. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Strategies for carbohydrate model building, refinement and validation.

    PubMed

    Agirre, Jon

    2017-02-01

    Sugars are the most stereochemically intricate family of biomolecules and present substantial challenges to anyone trying to understand their nomenclature, reactions or branched structures. Current crystallographic programs provide an abstraction layer allowing inexpert structural biologists to build complete protein or nucleic acid model components automatically either from scratch or with little manual intervention. This is, however, still not generally true for sugars. The need for carbohydrate-specific building and validation tools has been highlighted a number of times in the past, concomitantly with the introduction of a new generation of experimental methods that have been ramping up the production of protein-sugar complexes and glycoproteins for the past decade. While some incipient advances have been made to address these demands, correctly modelling and refining carbohydrates remains a challenge. This article will address many of the typical difficulties that a structural biologist may face when dealing with carbohydrates, with an emphasis on problem solving in the resolution range where X-ray crystallography and cryo-electron microscopy are expected to overlap in the next decade.

  13. THz spectroscopy: An emerging technology for pharmaceutical development and pharmaceutical Process Analytical Technology (PAT) applications

    NASA Astrophysics Data System (ADS)

    Wu, Huiquan; Khan, Mansoor

    2012-08-01

    As an emerging technology, THz spectroscopy has gained increasing attention in the pharmaceutical area during the last decade. This attention is due to the fact that (1) it provides a promising alternative approach for in-depth understanding of both intermolecular interaction among pharmaceutical molecules and pharmaceutical product quality attributes; (2) it provides a promising alternative approach for enhanced process understanding of certain pharmaceutical manufacturing processes; and (3) the FDA pharmaceutical quality initiatives, most noticeably, the Process Analytical Technology (PAT) initiative. In this work, the current status and progress made so far on using THz spectroscopy for pharmaceutical development and pharmaceutical PAT applications are reviewed. In the spirit of demonstrating the utility of first principles modeling approach for addressing model validation challenge and reducing unnecessary model validation "burden" for facilitating THz pharmaceutical PAT applications, two scientific case studies based on published THz spectroscopy measurement results are created and discussed. Furthermore, other technical challenges and opportunities associated with adapting THz spectroscopy as a pharmaceutical PAT tool are highlighted.

  14. Water Stress on U.S. Power Production at Decadal Time Horizons

    NASA Astrophysics Data System (ADS)

    Ganguli, P.; Kumar, D.; Yun, J.; Short, G.; Klausner, J.; Ganguly, A. R.

    2014-12-01

    Thermoelectric power production at risk, owing to current and projected water scarcity and rising stream temperatures, is assessed for the continental United States (US) at decadal scales. Regional water scarcity is driven by climate variability and change, as well as by multi-sector water demand. While a planning horizon of zero to about thirty years is occasionally prescribed by stakeholders, the challenges to risk assessment at these scales include the difficulty in delineating decadal climate trends from intrinsic natural or multiple model variability. Current generation global climate or earth system models are not credible at the spatial resolutions of power plants, especially for surface water quantity and stream temperatures, which further exacerbates the assessment challenge. Population changes, which are anyway difficult to project, cannot serve as adequate proxies for changes in the water demand across sectors. The hypothesis that robust assessments of power production at risks are possible, despite the uncertainties, has been examined as a proof of concept. An approach is presented for delineating water scarcity and temperature from climate models, observations and population storylines, as well as for assessing power production at risk by examining geospatial correlations of power plant locations within regions where the usable water supply for energy production happens to be scarcer and warmer. Acknowledgment: Funding provided by US DOE's ARPA-E through Award DE-AR0000374.

  15. SparRec: An effective matrix completion framework of missing data imputation for GWAS

    NASA Astrophysics Data System (ADS)

    Jiang, Bo; Ma, Shiqian; Causey, Jason; Qiao, Linbo; Hardin, Matthew Price; Bitts, Ian; Johnson, Daniel; Zhang, Shuzhong; Huang, Xiuzhen

    2016-10-01

    Genome-wide association studies present computational challenges for missing data imputation, while the advances of genotype technologies are generating datasets of large sample sizes with sample sets genotyped on multiple SNP chips. We present a new framework SparRec (Sparse Recovery) for imputation, with the following properties: (1) The optimization models of SparRec, based on low-rank and low number of co-clusters of matrices, are different from current statistics methods. While our low-rank matrix completion (LRMC) model is similar to Mendel-Impute, our matrix co-clustering factorization (MCCF) model is completely new. (2) SparRec, as other matrix completion methods, is flexible to be applied to missing data imputation for large meta-analysis with different cohorts genotyped on different sets of SNPs, even when there is no reference panel. This kind of meta-analysis is very challenging for current statistics based methods. (3) SparRec has consistent performance and achieves high recovery accuracy even when the missing data rate is as high as 90%. Compared with Mendel-Impute, our low-rank based method achieves similar accuracy and efficiency, while the co-clustering based method has advantages in running time. The testing results show that SparRec has significant advantages and competitive performance over other state-of-the-art existing statistics methods including Beagle and fastPhase.

  16. A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics.

    PubMed

    Chang, C C; Nicholson, A N; Rinaldi, E; Berkowitz, E; Garron, N; Brantley, D A; Monge-Camacho, H; Monahan, C J; Bouchard, C; Clark, M A; Joó, B; Kurth, T; Orginos, K; Vranas, P; Walker-Loud, A

    2018-06-01

    The axial coupling of the nucleon, g A , is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of g A makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome 1,2 : contamination of g A from excited states must be controlled in the calculations and statistical precision must be improved markedly 2-10 . Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a g A value of 1.271 ± 0.013, which has a precision of about one per cent.

  17. A systematic approach for the accurate non-invasive estimation of blood glucose utilizing a novel light-tissue interaction adaptive modelling scheme

    NASA Astrophysics Data System (ADS)

    Rybynok, V. O.; Kyriacou, P. A.

    2007-10-01

    Diabetes is one of the biggest health challenges of the 21st century. The obesity epidemic, sedentary lifestyles and an ageing population mean prevalence of the condition is currently doubling every generation. Diabetes is associated with serious chronic ill health, disability and premature mortality. Long-term complications including heart disease, stroke, blindness, kidney disease and amputations, make the greatest contribution to the costs of diabetes care. Many of these long-term effects could be avoided with earlier, more effective monitoring and treatment. Currently, blood glucose can only be monitored through the use of invasive techniques. To date there is no widely accepted and readily available non-invasive monitoring technique to measure blood glucose despite the many attempts. This paper challenges one of the most difficult non-invasive monitoring techniques, that of blood glucose, and proposes a new novel approach that will enable the accurate, and calibration free estimation of glucose concentration in blood. This approach is based on spectroscopic techniques and a new adaptive modelling scheme. The theoretical implementation and the effectiveness of the adaptive modelling scheme for this application has been described and a detailed mathematical evaluation has been employed to prove that such a scheme has the capability of extracting accurately the concentration of glucose from a complex biological media.

  18. Recapitulation of complex transport and action of drugs at tumor microenvironment using tumor-microenvironment-on-chip

    PubMed Central

    Han, Bumsoo; Qu, Chunjing; Park, Kinam; Konieczny, Stephen F.; Korc, Murray

    2016-01-01

    Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed. PMID:26688098

  19. Toward a Transdisciplinary Model of Evidence-Based Practice

    PubMed Central

    Satterfield, Jason M; Spring, Bonnie; Brownson, Ross C; Mullen, Edward J; Newhouse, Robin P; Walker, Barbara B; Whitlock, Evelyn P

    2009-01-01

    Context This article describes the historical context and current developments in evidence-based practice (EBP) for medicine, nursing, psychology, social work, and public health, as well as the evolution of the seminal “three circles” model of evidence-based medicine, highlighting changes in EBP content, processes, and philosophies across disciplines. Methods The core issues and challenges in EBP are identified by comparing and contrasting EBP models across various health disciplines. Then a unified, transdisciplinary EBP model is presented, drawing on the strengths and compensating for the weaknesses of each discipline. Findings Common challenges across disciplines include (1) how “evidence” should be defined and comparatively weighted; (2) how and when the patient's and/or other contextual factors should enter the clinical decision-making process; (3) the definition and role of the “expert”; and (4) what other variables should be considered when selecting an evidence-based practice, such as age, social class, community resources, and local expertise. Conclusions A unified, transdisciplinary EBP model would address historical shortcomings by redefining the contents of each model circle, clarifying the practitioner's expertise and competencies, emphasizing shared decision making, and adding both environmental and organizational contexts. Implications for academia, practice, and policy also are discussed. PMID:19523122

  20. Health Information System in Primary Health Care: The Challenges and Barriers from Local Providers’ Perspective of an Area in Iran

    PubMed Central

    Yazdi-Feyzabadi, Vahid; Emami, Mozhgan; Mehrolhassani, Mohammad Hossein

    2015-01-01

    Background: Health information system (HIS) has been utilized for collecting, processing, storing, and transferring the required information for planning and decision-making at different levels of health sector to provide quality services. In this study, in order to provide high-quality HIS, primary health care (PHC) providers’ perspective on current challenges and barriers were investigated. Methods: This study was carried out with a qualitative approach using semi-structured audiotaped focus group discussions (FGDs). One FGD was conducted with 13 Behvarz and health technicians as front-line workers and the other with 16 personnel including physicians, statisticians, and health professionals working in health centers of the PHC network in KUMS. The discussions were transcribed and then analyzed using the framework analysis method. Results: The identified organizational challenges were categorized into two groups: HIS structure and the current model of PHC in urban areas. Furthermore, the structural challenges were classified into HIS management structure (information systems resources, including human, supplies, and organizational rules) and information process. Conclusions: The HIS works effectively and efficiently when there are a consistency and integrity between the human, supplies, and process aspects. Hence, multifaceted interventions including strengthening the organizational culture to use the information in decisions, eliminating infrastructural obstacles, appointing qualified staff and more investment for service delivery at urban areas are the most fundamental requirements of high-quality HIS in PHC. PMID:26236444

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