Sample records for multi site complexation

  1. The ability of multi-site, multi-depth sacral lateral branch blocks to anesthetize the sacroiliac joint complex.

    PubMed

    Dreyfuss, Paul; Henning, Troy; Malladi, Niriksha; Goldstein, Barry; Bogduk, Nikolai

    2009-01-01

    To determine the physiologic effectiveness of multi-site, multi-depth sacral lateral branch injections. Double-blind, randomized, placebo-controlled study. Outpatient pain management center. Twenty asymptomatic volunteers. The dorsal innervation to the sacroiliac joint (SIJ) is from the L5 dorsal ramus and the S1-3 lateral branches. Multi-site, multi-depth lateral branch blocks were developed to compensate for the complex regional anatomy that limited the effectiveness of single-site, single-depth lateral branch injections. Bilateral multi-site, multi-depth lateral branch green dye injections and subsequent dissection on two cadavers revealed a 91% accuracy with this technique. Session 1: 20 asymptomatic subjects had a 25-g spinal needle probe their interosseous (IO) and dorsal sacroiliac (DSI) ligaments. The inferior dorsal SIJ was entered and capsular distension with contrast medium was performed. Discomfort had to occur with each provocation maneuver and a contained arthrogram was necessary to continue in the study. Session 2: 1 week later; computer randomized, double-blind multi-site, multi-depth lateral branch blocks injections were performed. Ten subjects received active (bupivicaine 0.75%) and 10 subjects received sham (normal saline) multi-site, multi-depth lateral branch injections. Thirty minutes later, provocation testing was repeated with identical methodology used in session 1. Presence or absence of pain for ligamentous probing and SIJ capsular distension. Seventy percent of the active group had an insensate IO and DSI ligaments, and inferior dorsal SIJ vs 0-10% of the sham group. Twenty percent of the active vs 10% of the sham group did not feel repeat capsular distension. Six of seven subjects (86%) retained the ability to feel repeat capsular distension despite an insensate dorsal SIJ complex. Multi-site, multi-depth lateral branch blocks are physiologically effective at a rate of 70%. Multi-site, multi-depth lateral branch blocks do not effectively block the intra-articular portion of the SIJ. There is physiological evidence that the intra-articular portion of the SIJ is innervated from both ventral and dorsal sources. Comparative multi-site, multi-depth lateral branch blocks should be considered a potentially valuable tool to diagnose extra-articular SIJ pain and determine if lateral branch radiofrequency neurotomy may assist one with SIJ pain.

  2. Reduced-complexity multi-site rainfall generation: one million years over night using the model TripleM

    NASA Astrophysics Data System (ADS)

    Breinl, Korbinian; Di Baldassarre, Giuliano; Girons Lopez, Marc

    2017-04-01

    We assess uncertainties of multi-site rainfall generation across spatial scales and different climatic conditions. Many research subjects in earth sciences such as floods, droughts or water balance simulations require the generation of long rainfall time series. In large study areas the simulation at multiple sites becomes indispensable to account for the spatial rainfall variability, but becomes more complex compared to a single site due to the intermittent nature of rainfall. Weather generators can be used for extrapolating rainfall time series, and various models have been presented in the literature. Even though the large majority of multi-site rainfall generators is based on similar methods, such as resampling techniques or Markovian processes, they often become too complex. We think that this complexity has been a limit for the application of such tools. Furthermore, the majority of multi-site rainfall generators found in the literature are either not publicly available or intended for being applied at small geographical scales, often only in temperate climates. Here we present a revised, and now publicly available, version of a multi-site rainfall generation code first applied in 2014 in Austria and France, which we call TripleM (Multisite Markov Model). We test this fast and robust code with daily rainfall observations from the United States, in a subtropical, tropical and temperate climate, using rain gauge networks with a maximum site distance above 1,000km, thereby generating one million years of synthetic time series. The modelling of these one million years takes one night on a recent desktop computer. In this research, we first start the simulations with a small station network of three sites and progressively increase the number of sites and the spatial extent, and analyze the changing uncertainties for multiple statistical metrics such as dry and wet spells, rainfall autocorrelation, lagged cross correlations and the inter-annual rainfall variability. Our study contributes to the scientific community of earth sciences and the ongoing debate on extreme precipitation in a changing climate by making a stable, and very easily applicable, multi-site rainfall generation code available to the research community and providing a better understanding of the performance of multi-site rainfall generation depending on spatial scales and climatic conditions.

  3. a Multi-Data Source and Multi-Sensor Approach for the 3d Reconstruction and Visualization of a Complex Archaelogical Site: the Case Study of Tolmo de Minateda

    NASA Astrophysics Data System (ADS)

    Torres-Martínez, J. A.; Seddaiu, M.; Rodríguez-Gonzálvez, P.; Hernández-López, D.; González-Aguilera, D.

    2015-02-01

    The complexity of archaeological sites hinders to get an integral modelling using the actual Geomatic techniques (i.e. aerial, closerange photogrammetry and terrestrial laser scanner) individually, so a multi-sensor approach is proposed as the best solution to provide a 3D reconstruction and visualization of these complex sites. Sensor registration represents a riveting milestone when automation is required and when aerial and terrestrial dataset must be integrated. To this end, several problems must be solved: coordinate system definition, geo-referencing, co-registration of point clouds, geometric and radiometric homogeneity, etc. Last but not least, safeguarding of tangible archaeological heritage and its associated intangible expressions entails a multi-source data approach in which heterogeneous material (historical documents, drawings, archaeological techniques, habit of living, etc.) should be collected and combined with the resulting hybrid 3D of "Tolmo de Minateda" located models. The proposed multi-data source and multi-sensor approach is applied to the study case of "Tolmo de Minateda" archaeological site. A total extension of 9 ha is reconstructed, with an adapted level of detail, by an ultralight aerial platform (paratrike), an unmanned aerial vehicle, a terrestrial laser scanner and terrestrial photogrammetry. In addition, the own defensive nature of the site (i.e. with the presence of three different defensive walls) together with the considerable stratification of the archaeological site (i.e. with different archaeological surfaces and constructive typologies) require that tangible and intangible archaeological heritage expressions can be integrated with the hybrid 3D models obtained, to analyse, understand and exploit the archaeological site by different experts and heritage stakeholders.

  4. Biphasic responses in multi-site phosphorylation systems.

    PubMed

    Suwanmajo, Thapanar; Krishnan, J

    2013-12-06

    Multi-site phosphorylation systems are repeatedly encountered in cellular biology and multi-site modification is a basic building block of post-translational modification. In this paper, we demonstrate how distributive multi-site modification mechanisms by a single kinase/phosphatase pair can lead to biphasic/partial biphasic dose-response characteristics for the maximally phosphorylated substrate at steady state. We use simulations and analysis to uncover a hidden competing effect which is responsible for this and analyse how it may be accentuated. We build on this to analyse different variants of multi-site phosphorylation mechanisms showing that some mechanisms are intrinsically not capable of displaying this behaviour. This provides both a consolidated understanding of how and under what conditions biphasic responses are obtained in multi-site phosphorylation and a basis for discriminating between different mechanisms based on this. We also demonstrate how this behaviour may be combined with other behaviour such as threshold and bistable responses, demonstrating the capacity of multi-site phosphorylation systems to act as complex molecular signal processors.

  5. Progress in centralised ethics review processes: Implications for multi-site health evaluations.

    PubMed

    Prosser, Brenton; Davey, Rachel; Gibson, Diane

    2015-04-01

    Increasingly, public sector programmes respond to complex social problems that intersect specific fields and individual disciplines. Such responses result in multi-site initiatives that can span nations, jurisdictions, sectors and organisations. The rigorous evaluation of public sector programmes is now a baseline expectation. For evaluations of large and complex multi-site programme initiatives, the processes of ethics review can present a significant challenge. However in recent years, there have been new developments in centralised ethics review processes in many nations. This paper provides the case study of an evaluation of a national, inter-jurisdictional, cross-sector, aged care health initiative and its encounters with Australian centralised ethics review processes. Specifically, the paper considers progress against the key themes of a previous five-year, five nation study (Fitzgerald and Phillips, 2006), which found that centralised ethics review processes would save time, money and effort, as well as contribute to more equitable workloads for researchers and evaluators. The paper concludes with insights for those charged with refining centralised ethics review processes, as well as recommendations for future evaluators of complex multi-site programme initiatives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. CMS Readiness for Multi-Core Workload Scheduling

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

    Perez-Calero Yzquierdo, A.; Balcas, J.; Hernandez, J.

    In the present run of the LHC, CMS data reconstruction and simulation algorithms benefit greatly from being executed as multiple threads running on several processor cores. The complexity of the Run 2 events requires parallelization of the code to reduce the memory-per- core footprint constraining serial execution programs, thus optimizing the exploitation of present multi-core processor architectures. The allocation of computing resources for multi-core tasks, however, becomes a complex problem in itself. The CMS workload submission infrastructure employs multi-slot partitionable pilots, built on HTCondor and GlideinWMS native features, to enable scheduling of single and multi-core jobs simultaneously. This provides amore » solution for the scheduling problem in a uniform way across grid sites running a diversity of gateways to compute resources and batch system technologies. This paper presents this strategy and the tools on which it has been implemented. The experience of managing multi-core resources at the Tier-0 and Tier-1 sites during 2015, along with the deployment phase to Tier-2 sites during early 2016 is reported. The process of performance monitoring and optimization to achieve efficient and flexible use of the resources is also described.« less

  7. CMS readiness for multi-core workload scheduling

    NASA Astrophysics Data System (ADS)

    Perez-Calero Yzquierdo, A.; Balcas, J.; Hernandez, J.; Aftab Khan, F.; Letts, J.; Mason, D.; Verguilov, V.

    2017-10-01

    In the present run of the LHC, CMS data reconstruction and simulation algorithms benefit greatly from being executed as multiple threads running on several processor cores. The complexity of the Run 2 events requires parallelization of the code to reduce the memory-per- core footprint constraining serial execution programs, thus optimizing the exploitation of present multi-core processor architectures. The allocation of computing resources for multi-core tasks, however, becomes a complex problem in itself. The CMS workload submission infrastructure employs multi-slot partitionable pilots, built on HTCondor and GlideinWMS native features, to enable scheduling of single and multi-core jobs simultaneously. This provides a solution for the scheduling problem in a uniform way across grid sites running a diversity of gateways to compute resources and batch system technologies. This paper presents this strategy and the tools on which it has been implemented. The experience of managing multi-core resources at the Tier-0 and Tier-1 sites during 2015, along with the deployment phase to Tier-2 sites during early 2016 is reported. The process of performance monitoring and optimization to achieve efficient and flexible use of the resources is also described.

  8. Assessing intervention fidelity in a multi-level, multi-component, multi-site program: the Children's Healthy Living (CHL) program.

    PubMed

    Butel, Jean; Braun, Kathryn L; Novotny, Rachel; Acosta, Mark; Castro, Rose; Fleming, Travis; Powers, Julianne; Nigg, Claudio R

    2015-12-01

    Addressing complex chronic disease prevention, like childhood obesity, requires a multi-level, multi-component culturally relevant approach with broad reach. Models are lacking to guide fidelity monitoring across multiple levels, components, and sites engaged in such interventions. The aim of this study is to describe the fidelity-monitoring approach of The Children's Healthy Living (CHL) Program, a multi-level multi-component intervention in five Pacific jurisdictions. A fidelity-monitoring rubric was developed. About halfway during the intervention, community partners were randomly selected and interviewed independently by local CHL staff and by Coordinating Center representatives to assess treatment fidelity. Ratings were compared and discussed by local and Coordinating Center staff. There was good agreement between the teams (Kappa = 0.50, p < 0.001), and intervention improvement opportunities were identified through data review and group discussion. Fidelity for the multi-level, multi-component, multi-site CHL intervention was successfully assessed, identifying adaptations as well as ways to improve intervention delivery prior to the end of the intervention.

  9. Combining biophysical methods for the analysis of protein complex stoichiometry and affinity in SEDPHAT

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

    Zhao, Huaying, E-mail: zhaoh3@mail.nih.gov; Schuck, Peter, E-mail: zhaoh3@mail.nih.gov

    2015-01-01

    Global multi-method analysis for protein interactions (GMMA) can increase the precision and complexity of binding studies for the determination of the stoichiometry, affinity and cooperativity of multi-site interactions. The principles and recent developments of biophysical solution methods implemented for GMMA in the software SEDPHAT are reviewed, their complementarity in GMMA is described and a new GMMA simulation tool set in SEDPHAT is presented. Reversible macromolecular interactions are ubiquitous in signal transduction pathways, often forming dynamic multi-protein complexes with three or more components. Multivalent binding and cooperativity in these complexes are often key motifs of their biological mechanisms. Traditional solution biophysicalmore » techniques for characterizing the binding and cooperativity are very limited in the number of states that can be resolved. A global multi-method analysis (GMMA) approach has recently been introduced that can leverage the strengths and the different observables of different techniques to improve the accuracy of the resulting binding parameters and to facilitate the study of multi-component systems and multi-site interactions. Here, GMMA is described in the software SEDPHAT for the analysis of data from isothermal titration calorimetry, surface plasmon resonance or other biosensing, analytical ultracentrifugation, fluorescence anisotropy and various other spectroscopic and thermodynamic techniques. The basic principles of these techniques are reviewed and recent advances in view of their particular strengths in the context of GMMA are described. Furthermore, a new feature in SEDPHAT is introduced for the simulation of multi-method data. In combination with specific statistical tools for GMMA in SEDPHAT, simulations can be a valuable step in the experimental design.« less

  10. Research of diagnosis sensors fault based on correlation analysis of the bridge structural health monitoring system

    NASA Astrophysics Data System (ADS)

    Hu, Shunren; Chen, Weimin; Liu, Lin; Gao, Xiaoxia

    2010-03-01

    Bridge structural health monitoring system is a typical multi-sensor measurement system due to the multi-parameters of bridge structure collected from the monitoring sites on the river-spanning bridges. Bridge structure monitored by multi-sensors is an entity, when subjected to external action; there will be different performances to different bridge structure parameters. Therefore, the data acquired by each sensor should exist countless correlation relation. However, complexity of the correlation relation is decided by complexity of bridge structure. Traditionally correlation analysis among monitoring sites is mainly considered from physical locations. unfortunately, this method is so simple that it cannot describe the correlation in detail. The paper analyzes the correlation among the bridge monitoring sites according to the bridge structural data, defines the correlation of bridge monitoring sites and describes its several forms, then integrating the correlative theory of data mining and signal system to establish the correlation model to describe the correlation among the bridge monitoring sites quantificationally. Finally, The Chongqing Mashangxi Yangtze river bridge health measurement system is regards as research object to diagnosis sensors fault, and simulation results verify the effectiveness of the designed method and theoretical discussions.

  11. Genetic code expansion for multiprotein complex engineering.

    PubMed

    Koehler, Christine; Sauter, Paul F; Wawryszyn, Mirella; Girona, Gemma Estrada; Gupta, Kapil; Landry, Jonathan J M; Fritz, Markus Hsi-Yang; Radic, Ksenija; Hoffmann, Jan-Erik; Chen, Zhuo A; Zou, Juan; Tan, Piau Siong; Galik, Bence; Junttila, Sini; Stolt-Bergner, Peggy; Pruneri, Giancarlo; Gyenesei, Attila; Schultz, Carsten; Biskup, Moritz Bosse; Besir, Hueseyin; Benes, Vladimir; Rappsilber, Juri; Jechlinger, Martin; Korbel, Jan O; Berger, Imre; Braese, Stefan; Lemke, Edward A

    2016-12-01

    We present a baculovirus-based protein engineering method that enables site-specific introduction of unique functionalities in a eukaryotic protein complex recombinantly produced in insect cells. We demonstrate the versatility of this efficient and robust protein production platform, 'MultiBacTAG', (i) for the fluorescent labeling of target proteins and biologics using click chemistries, (ii) for glycoengineering of antibodies, and (iii) for structure-function studies of novel eukaryotic complexes using single-molecule Förster resonance energy transfer as well as site-specific crosslinking strategies.

  12. Evaluation of stormwater harvesting sites using multi criteria decision methodology

    NASA Astrophysics Data System (ADS)

    Inamdar, P. M.; Sharma, A. K.; Cook, Stephen; Perera, B. J. C.

    2018-07-01

    Selection of suitable urban stormwater harvesting sites and associated project planning are often complex due to spatial, temporal, economic, environmental and social factors, and related various other variables. This paper is aimed at developing a comprehensive methodology framework for evaluating of stormwater harvesting sites in urban areas using Multi Criteria Decision Analysis (MCDA). At the first phase, framework selects potential stormwater harvesting (SWH) sites using spatial characteristics in a GIS environment. In second phase, MCDA methodology is used for evaluating and ranking of SWH sites in multi-objective and multi-stakeholder environment. The paper briefly describes first phase of framework and focuses chiefly on the second phase of framework. The application of the methodology is also demonstrated over a case study comprising of the local government area, City of Melbourne (CoM), Australia for the benefit of wider water professionals engaged in this area. Nine performance measures (PMs) were identified to characterise the objectives and system performance related to the eight alternative SWH sites for the demonstration of the application of developed methodology. To reflect the stakeholder interests in the current study, four stakeholder participant groups were identified, namely, water authorities (WA), academics (AC), consultants (CS), and councils (CL). The decision analysis methodology broadly consisted of deriving PROMETHEE II rankings of eight alternative SWH sites in the CoM case study, under two distinct group decision making scenarios. The major innovation of this work is the development and application of comprehensive methodology framework that assists in the selection of potential sites for SWH, and facilitates the ranking in multi-objective and multi-stakeholder environment. It is expected that the proposed methodology will assist the water professionals and managers with better knowledge that will reduce the subjectivity in the selection and evaluation of SWH sites.

  13. Artificial Metalloproteins Containing Co 4O 4Cubane Active Sites

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

    Olshansky, Lisa; Huerta-Lavorie, Raul; Nguyen, Andy I.

    Artificial metalloproteins (ArMs) containing Co 4O 4 cubane active sites were constructed via biotin-streptavidin technology. Stabilized by hydrogen bonds (H-bonds), terminal and cofacial Co III-OH 2 moieties are observed crystallographically in a series of immobilized cubane sites. Solution electrochemistry provided correlations of oxidation potential and pH. For variants containing Ser and Phe adjacent to the metallocofactor, 1e -/1H + chemistry predominates until pH 8, above which the oxidation becomes pH-independent. Installation of Tyr proximal to the Co 4O 4 active site provided a single H-bond to one of a set of cofacial Co III-OH 2 groups. With this variant, multi-emore » - /multi-H + chemistry is observed, along with a change in mechanism at pH 9.5 that is consistent with Tyr deprotonation. Finally, with structural similarities to both the oxygen-evolving complex of photosystem II (H-bonded Tyr) and to thin film water oxidation catalysts (Co 4O 4 core), these findings bridge synthetic and biological systems for water oxidation, highlighting the importance of secondary sphere interactions in mediating multi-e - /multi-H + reactivity.« less

  14. Artificial Metalloproteins Containing Co 4O 4Cubane Active Sites

    DOE PAGES

    Olshansky, Lisa; Huerta-Lavorie, Raul; Nguyen, Andy I.; ...

    2018-02-05

    Artificial metalloproteins (ArMs) containing Co 4O 4 cubane active sites were constructed via biotin-streptavidin technology. Stabilized by hydrogen bonds (H-bonds), terminal and cofacial Co III-OH 2 moieties are observed crystallographically in a series of immobilized cubane sites. Solution electrochemistry provided correlations of oxidation potential and pH. For variants containing Ser and Phe adjacent to the metallocofactor, 1e -/1H + chemistry predominates until pH 8, above which the oxidation becomes pH-independent. Installation of Tyr proximal to the Co 4O 4 active site provided a single H-bond to one of a set of cofacial Co III-OH 2 groups. With this variant, multi-emore » - /multi-H + chemistry is observed, along with a change in mechanism at pH 9.5 that is consistent with Tyr deprotonation. Finally, with structural similarities to both the oxygen-evolving complex of photosystem II (H-bonded Tyr) and to thin film water oxidation catalysts (Co 4O 4 core), these findings bridge synthetic and biological systems for water oxidation, highlighting the importance of secondary sphere interactions in mediating multi-e - /multi-H + reactivity.« less

  15. Accelerating and focusing protein-protein docking correlations using multi-dimensional rotational FFT generating functions.

    PubMed

    Ritchie, David W; Kozakov, Dima; Vajda, Sandor

    2008-09-01

    Predicting how proteins interact at the molecular level is a computationally intensive task. Many protein docking algorithms begin by using fast Fourier transform (FFT) correlation techniques to find putative rigid body docking orientations. Most such approaches use 3D Cartesian grids and are therefore limited to computing three dimensional (3D) translational correlations. However, translational FFTs can speed up the calculation in only three of the six rigid body degrees of freedom, and they cannot easily incorporate prior knowledge about a complex to focus and hence further accelerate the calculation. Furthemore, several groups have developed multi-term interaction potentials and others use multi-copy approaches to simulate protein flexibility, which both add to the computational cost of FFT-based docking algorithms. Hence there is a need to develop more powerful and more versatile FFT docking techniques. This article presents a closed-form 6D spherical polar Fourier correlation expression from which arbitrary multi-dimensional multi-property multi-resolution FFT correlations may be generated. The approach is demonstrated by calculating 1D, 3D and 5D rotational correlations of 3D shape and electrostatic expansions up to polynomial order L=30 on a 2 GB personal computer. As expected, 3D correlations are found to be considerably faster than 1D correlations but, surprisingly, 5D correlations are often slower than 3D correlations. Nonetheless, we show that 5D correlations will be advantageous when calculating multi-term knowledge-based interaction potentials. When docking the 84 complexes of the Protein Docking Benchmark, blind 3D shape plus electrostatic correlations take around 30 minutes on a contemporary personal computer and find acceptable solutions within the top 20 in 16 cases. Applying a simple angular constraint to focus the calculation around the receptor binding site produces acceptable solutions within the top 20 in 28 cases. Further constraining the search to the ligand binding site gives up to 48 solutions within the top 20, with calculation times of just a few minutes per complex. Hence the approach described provides a practical and fast tool for rigid body protein-protein docking, especially when prior knowledge about one or both binding sites is available.

  16. Prioritizing ecological restoration among sites in multi-stressor landscapes.

    PubMed

    Neeson, Thomas M; Smith, Sigrid D P; Allan, J David; McIntyre, Peter B

    2016-09-01

    Most ecosystems are impacted by multiple local and long-distance stressors, many of which interact in complex ways. We present a framework for prioritizing ecological restoration efforts among sites in multi-stressor landscapes. Using a simple model, we show that both the economic and sociopolitical costs of restoration will typically be lower at sites with a relatively small number of severe problems than at sites with numerous lesser problems. Based on these results, we propose using cumulative stress and evenness of stressor impact as complementary indices that together reflect key challenges of restoring a site to improved condition. To illustrate this approach, we analyze stressor evenness across the world's rivers and the Laurentian Great Lakes. This exploration reveals that evenness and cumulative stress are decoupled, enabling selection of sites where remediating a modest number of high-intensity stressors could substantially reduce cumulative stress. Just as species richness and species evenness are fundamental axes of biological diversity, we argue that cumulative stress and stressor evenness constitute fundamental axes for identifying restoration opportunities in multi-stressor landscapes. Our results highlight opportunities to boost restoration efficiency through strategic use of multi-stressor datasets to identify sites that maximize ecological response per stressor remediated. This prioritization framework can also be expanded to account for the feasibility of remediation and the expected societal benefits of restoration projects. © 2016 by the Ecological Society of America.

  17. Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm

    NASA Astrophysics Data System (ADS)

    Fu, Jinglin; Yang, Yuhe Renee; Johnson-Buck, Alexander; Liu, Minghui; Liu, Yan; Walter, Nils G.; Woodbury, Neal W.; Yan, Hao

    2014-07-01

    Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein-DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

  18. Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm.

    PubMed

    Fu, Jinglin; Yang, Yuhe Renee; Johnson-Buck, Alexander; Liu, Minghui; Liu, Yan; Walter, Nils G; Woodbury, Neal W; Yan, Hao

    2014-07-01

    Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein-DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

  19. Mixed mechanisms of multi-site phosphorylation

    PubMed Central

    Suwanmajo, Thapanar; Krishnan, J.

    2015-01-01

    Multi-site phosphorylation is ubiquitous in cell biology and has been widely studied experimentally and theoretically. The underlying chemical modification mechanisms are typically assumed to be distributive or processive. In this paper, we study the behaviour of mixed mechanisms that can arise either because phosphorylation and dephosphorylation involve different mechanisms or because phosphorylation and/or dephosphorylation can occur through a combination of mechanisms. We examine a hierarchy of models to assess chemical information processing through different mixed mechanisms, using simulations, bifurcation analysis and analytical work. We demonstrate how mixed mechanisms can show important and unintuitive differences from pure distributive and processive mechanisms, in some cases resulting in monostable behaviour with simple dose–response behaviour, while in other cases generating new behaviour-like oscillations. Our results also suggest patterns of information processing that are relevant as the number of modification sites increases. Overall, our work creates a framework to examine information processing arising from complexities of multi-site modification mechanisms and their impact on signal transduction. PMID:25972433

  20. Planning a multi-site, complex intervention for homeless people with mental illness: the relationships between the national team and local sites in Canada's At Home/Chez Soi project.

    PubMed

    Nelson, Geoffrey; Macnaughton, Eric; Goering, Paula; Dudley, Michael; O'Campo, Patricia; Patterson, Michelle; Piat, Myra; Prévost, Natasha; Strehlau, Verena; Vallée, Catherine

    2013-06-01

    This research focused on the relationships between a national team and five project sites across Canada in planning a complex, community intervention for homeless people with mental illness called At Home/Chez Soi, which is based on the Housing First model. The research addressed two questions: (a) what are the challenges in planning? and (b) what factors that helped or hindered moving project planning forward? Using qualitative methods, 149 national, provincial, and local stakeholders participated in key informant or focus group interviews. We found that planning entails not only intervention and research tasks, but also relational processes that occur within an ecology of time, local context, and values. More specifically, the relationships between the national team and the project sites can be conceptualized as a collaborative process in which national and local partners bring different agendas to the planning process and must therefore listen to, negotiate, discuss, and compromise with one another. A collaborative process that involves power-sharing and having project coordinators at each site helped to bridge the differences between these two stakeholder groups, to find common ground, and to accomplish planning tasks within a compressed time frame. While local context and culture pushed towards unique adaptations of Housing First, the principles of the Housing First model provided a foundation for a common approach across sites and interventions. The implications of the findings for future planning and research of multi-site, complex, community interventions are noted.

  1. Orthogonal use of a human tRNA synthetase active site to achieve multi-functionality

    PubMed Central

    Zhou, Quansheng; Kapoor, Mili; Guo, Min; Belani, Rajesh; Xu, Xiaoling; Kiosses, William B.; Hanan, Melanie; Park, Chulho; Armour, Eva; Do, Minh-Ha; Nangle, Leslie A.; Schimmel, Paul; Yang, Xiang-Lei

    2011-01-01

    Protein multi-functionality is an emerging explanation for the complexity of higher organisms. In this regard, while aminoacyl tRNA synthetases catalyze amino acid activation for protein synthesis, some also act in pathways for inflammation, angiogenesis, and apoptosis. How multiple functions evolved and their relationship to the active site is not clear. Here structural modeling analysis, mutagenesis, and cell-based functional studies show that the potent angiostatic, natural fragment of human TrpRS associates via Trp side chains that protrude from the cognate cellular receptor VE-cadherin. Modeling indicates that (I prefer the way it was because the conclusion was reached not only by modeling, but more so by experimental studies.)VE-cadherin Trp side chains fit into the Trp-specific active site of the synthetase. Thus, specific side chains of the receptor mimic (?) amino acid substrates and expand the functionality of the active site of the synthetase. We propose that orthogonal use of the same active site may be a general way to develop multi-functionality of human tRNA synthetases and other proteins. PMID:20010843

  2. Applying the Brakes to Multi-Site SR Protein Phosphorylation: Substrate-Induced Effects on the Splicing Kinase SRPK1†

    PubMed Central

    Aubol, Brandon E.; Adams, Joseph A.

    2011-01-01

    To investigate how a protein kinase interacts with its protein substrate during extended, multi-site phosphorylation, the kinetic mechanism of a protein kinase involved in mRNA splicing control was investigated using rapid quench flow techniques. The protein kinase SRPK1 phosphorylates approximately 10 serines in the arginine-serine-rich domain (RS domain) of the SR protein SRSF1 in a C-to-N-terminal direction, a modification that directs this essential splicing factor from the cytoplasm to the nucleus. Transient-state kinetic experiments illustrate that the first phosphate is added rapidly onto the RS domain of SRSF1 (t1/2 = 0.1 sec) followed by slower, multi-site phosphorylation at the remaining serines (t1/2 = 15 sec). Mutagenesis experiments suggest that efficient phosphorylation rates are maintained by an extensive hydrogen bonding and electrostatic network between the RS domain of the SR protein and the active site and docking groove of the kinase. Catalytic trapping and viscosometric experiments demonstrate that while the phosphoryl transfer step is fast, ADP release limits multi-site phosphorylation. By studying phosphate incorporation into selectively pre-phosphorylated forms of the enzyme-substrate complex, the kinetic mechanism for site-specific phosphorylation along the reaction coordinate was assessed. The binding affinity of the SR protein, the phosphoryl transfer rate and ADP exchange rate were found to decline significantly as a function of progressive phosphorylation in the RS domain. These findings indicate that the protein substrate actively modulates initiation, extension and termination events associated with prolonged, multi-site phosphorylation. PMID:21728354

  3. Methods of selectively incorporating metals onto substrates

    DOEpatents

    Ernst; Richard D. , Eyring; Edward M. , Turpin; Gregory C. , Dunn; Brian C.

    2008-09-30

    A method for forming multi-metallic sites on a substrate is disclosed and described. A substrate including active groups such as hydroxyl can be reacted with a pretarget metal complex. The target metal attached to the active group can then be reacted with a secondary metal complex such that an oxidation-reduction (redox) reaction occurs to form a multi-metallic species. The substrate can be a highly porous material such as aerogels, xerogels, zeolites, and similar materials. Additional metal complexes can be reacted to increase catalyst loading or control co-catalyst content. The resulting compounds can be oxidized to form oxides or reduced to form metals in the ground state which are suitable for practical use.

  4. Evaluating a complex, multi-site, community-based program to improve healthcare quality: the summative research design for the Aligning Forces for Quality initiative.

    PubMed

    Scanlon, Dennis P; Wolf, Laura J; Alexander, Jeffrey A; Christianson, Jon B; Greene, Jessica; Jean-Jacques, Muriel; McHugh, Megan; Shi, Yunfeng; Leitzell, Brigitt; Vanderbrink, Jocelyn M

    2016-08-01

    The Aligning Forces for Quality (AF4Q) initiative was the Robert Wood Johnson Foundation's (RWJF's) signature effort to increase the overall quality of healthcare in targeted communities throughout the country. In addition to sponsoring this 16-site complex program, RWJF funded an independent scientific evaluation to support objective research on the initiative's effectiveness and contributions to basic knowledge in 5 core programmatic areas. The research design, data, and challenges faced during the summative evaluation phase of this near decade-long program are discussed. A descriptive overview of the summative research design and its development for a multi-site, community-based, healthcare quality improvement initiative is provided. The summative research design employed by the evaluation team is discussed. The evaluation team's summative research design involved a data-driven assessment of the effectiveness of the AF4Q program at large, assessments of the impact of AF4Q in the specific programmatic areas, and an assessment of how the AF4Q alliances were positioned for the future at the end of the program. The AF4Q initiative was the largest privately funded community-based healthcare improvement initiative in the United States to date and was implemented at a time of rapid change in national healthcare policy. The implementation of large-scale, multi-site initiatives is becoming an increasingly common approach for addressing problems in healthcare. The summative evaluation research design for the AF4Q initiative, and the lessons learned from its approach, may be valuable to others tasked with evaluating similarly complex community-based initiatives.

  5. A progress report on the ARRA-funded geotechnical site characterization project

    NASA Astrophysics Data System (ADS)

    Martin, A. J.; Yong, A.; Stokoe, K.; Di Matteo, A.; Diehl, J.; Jack, S.

    2011-12-01

    For the past 18 months, the 2009 American Recovery and Reinvestment Act (ARRA) has funded geotechnical site characterizations at 189 seismographic station sites in California and the central U.S. This ongoing effort applies methods involving surface-wave techniques, which include the horizontal-to-vertical spectral ratio (HVSR) technique and one or more of the following: spectral analysis of surface wave (SASW), active and passive multi-channel analysis of surface wave (MASW) and passive array microtremor techniques. From this multi-method approach, shear-wave velocity profiles (VS) and the time-averaged shear-wave velocity of the upper 30 meters (VS30) are estimated for each site. To accommodate the variability in local conditions (e.g., rural and urban soil locales, as well as weathered and competent rock sites), conventional field procedures are often modified ad-hoc to fit the unanticipated complexity at each location. For the majority of sites (>80%), fundamental-mode Rayleigh wave dispersion-based techniques are deployed and where complex geology is encountered, multiple test locations are made. Due to the presence of high velocity layers, about five percent of the locations require multi-mode inversion of Rayleigh wave (MASW-based) data or 3-D array-based inversion of SASW dispersion data, in combination with shallow P-wave seismic refraction and/or HVSR results. Where a strong impedance contrast (i.e. soil over rock) exists at shallow depth (about 10% of sites), dominant higher modes limit the use of Rayleigh wave dispersion techniques. Here, use of the Love wave dispersion technique, along with seismic refraction and/or HVSR data, is required to model the presence of shallow bedrock. At a small percentage of the sites, surface wave techniques are found not suitable for stand-alone deployment and site characterization is limited to the use of the seismic refraction technique. A USGS Open File Report-describing the surface geology, VS profile and the calculated VS30 for each site-will be prepared after the completion of the project in November 2011.

  6. Development of policies for Natura 2000 sites: a multi-criteria approach to support decision makers.

    PubMed

    Cortina, Carla; Boggia, Antonio

    2014-08-01

    The aim of this study is to present a methodology to support decision makers in the choice of Natura 2000 sites needing an appropriate management plan to ensure a sustainable socio-economic development. In order to promote sustainable development in the Natura 2000 sites compatible with nature preservation, conservation measures or management plans are necessary. The main issue is to decide when only conservation measures can be applied and when the sites need an appropriate management plan. We present a case study for the Italian Region of Umbria. The methodology is based on a multi-criteria approach to identify the biodiversity index (BI), and on the development of a human activities index (HAI). By crossing the two indexes for each site on a Cartesian plane, four groups of sites were identified. Each group corresponds to a specific need for an appropriate management plan. Sites in the first group with a high level both of biodiversity and human activities have the most urgent need of an appropriate management plan to ensure sustainable development. The proposed methodology and analysis is replicable in other regions or countries by using the data available for each site in the Natura 2000 standard data form. A multi-criteria analysis is especially suitable for supporting decision makers when they deal with a multidimensional decision process. We found the multi-criteria approach particularly sound in this case, due to the concept of biodiversity itself, which is complex and multidimensional, and to the high number of alternatives (Natura 2000 sites) to be assessed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits.

    PubMed

    Wu, Yang; Zeng, Jian; Zhang, Futao; Zhu, Zhihong; Qi, Ting; Zheng, Zhili; Lloyd-Jones, Luke R; Marioni, Riccardo E; Martin, Nicholas G; Montgomery, Grant W; Deary, Ian J; Wray, Naomi R; Visscher, Peter M; McRae, Allan F; Yang, Jian

    2018-03-02

    The identification of genes and regulatory elements underlying the associations discovered by GWAS is essential to understanding the aetiology of complex traits (including diseases). Here, we demonstrate an analytical paradigm of prioritizing genes and regulatory elements at GWAS loci for follow-up functional studies. We perform an integrative analysis that uses summary-level SNP data from multi-omics studies to detect DNA methylation (DNAm) sites associated with gene expression and phenotype through shared genetic effects (i.e., pleiotropy). We identify pleiotropic associations between 7858 DNAm sites and 2733 genes. These DNAm sites are enriched in enhancers and promoters, and >40% of them are mapped to distal genes. Further pleiotropic association analyses, which link both the methylome and transcriptome to 12 complex traits, identify 149 DNAm sites and 66 genes, indicating a plausible mechanism whereby the effect of a genetic variant on phenotype is mediated by genetic regulation of transcription through DNAm.

  8. Multi-layer multi-configuration time-dependent Hartree (ML-MCTDH) approach to the correlated exciton-vibrational dynamics in the FMO complex

    NASA Astrophysics Data System (ADS)

    Schulze, Jan; Shibl, Mohamed F.; Al-Marri, Mohammed J.; Kühn, Oliver

    2016-05-01

    The coupled quantum dynamics of excitonic and vibrational degrees of freedom is investigated for high-dimensional models of the Fenna-Matthews-Olson complex. This includes a seven- and an eight-site model with 518 and 592 harmonic vibrational modes, respectively. The coupling between local electronic transitions and vibrations is described within the Huang-Rhys model using parameters that are obtained by discretization of an experimental spectral density. Different pathways of excitation energy flow are analyzed in terms of the reduced one-exciton density matrix, focussing on the role of vibrational and vibronic excitations. Distinct features due to both competing time scales of vibrational and exciton motion and vibronically assisted transfer are observed. The question of the effect of initial state preparation is addressed by comparing the case of an instantaneous Franck-Condon excitation at a single site with that of a laser field excitation.

  9. Satellite remote sensing of landscape freeze/thaw state dynamics for complex Topography and Fire Disturbance Areas Using multi-sensor radar and SRTM digital elevation models

    NASA Technical Reports Server (NTRS)

    Podest, Erika; McDonald, Kyle; Kimball, John; Randerson, James

    2003-01-01

    We characterize differences in radar-derived freeze/thaw state, examining transitions over complex terrain and landscape disturbance regimes. In areas of complex terrain, we explore freezekhaw dynamics related to elevation, slope aspect and varying landcover. In the burned regions, we explore the timing of seasonal freeze/thaw transition as related to the recovering landscape, relative to that of a nearby control site. We apply in situ biophysical measurements, including flux tower measurements to validate and interpret the remotely sensed parameters. A multi-scale analysis is performed relating high-resolution SAR backscatter and moderate resolution scatterometer measurements to assess trade-offs in spatial and temporal resolution in the remotely sensed fields.

  10. Uranium plume persistence impacted by hydrologic and geochemical heterogeneity in the groundwater and river water interaction zone of Hanford site

    NASA Astrophysics Data System (ADS)

    Chen, X.; Zachara, J. M.; Vermeul, V. R.; Freshley, M.; Hammond, G. E.

    2015-12-01

    The behavior of a persistent uranium plume in an extended groundwater- river water (GW-SW) interaction zone at the DOE Hanford site is dominantly controlled by river stage fluctuations in the adjacent Columbia River. The plume behavior is further complicated by substantial heterogeneity in physical and geochemical properties of the host aquifer sediments. Multi-scale field and laboratory experiments and reactive transport modeling were integrated to understand the complex plume behavior influenced by highly variable hydrologic and geochemical conditions in time and space. In this presentation we (1) describe multiple data sets from field-scale uranium adsorption and desorption experiments performed at our experimental well-field, (2) develop a reactive transport model that incorporates hydrologic and geochemical heterogeneities characterized from multi-scale and multi-type datasets and a surface complexation reaction network based on laboratory studies, and (3) compare the modeling and observation results to provide insights on how to refine the conceptual model and reduce prediction uncertainties. The experimental results revealed significant spatial variability in uranium adsorption/desorption behavior, while modeling demonstrated that ambient hydrologic and geochemical conditions and heterogeneities in sediment physical and chemical properties both contributed to complex plume behavior and its persistence. Our analysis provides important insights into the characterization, understanding, modeling, and remediation of groundwater contaminant plumes influenced by surface water and groundwater interactions.

  11. Citric Acid Enhanced Copper Removal by a Novel Multi-amines Decorated Resin

    PubMed Central

    Ling, Chen; Liu, Fuqiang; Pei, Zhiguo; Zhang, Xiaopeng; Wei, Mengmeng; Zhang, Yanhong; Zheng, Lirong; Zhang, Jing; Li, Aimin; Xing, Baoshan

    2015-01-01

    Cu removal by a novel multi-amines decorated resin (PAMD) from wastewater in the absence or presence of citric acid (CA) was examined. Adsorption capacity of Cu onto PAMD markedly increased by 186% to 5.07 mmol/g in the presence of CA, up to 7 times of that onto four commercial resins under the same conditions. Preloaded and kinetic studies demonstrated adsorption of [Cu-CA] complex instead of CA site-bridging and variations of adsorbate species were qualitatively illustrated. The interaction configuration was further studied with ESI-MS, FTIR, XPS and XANES characterizations. The large enhancement of Cu adsorption in Cu-CA bi-solutes systems was attributed to mechanism change from single-site to dual-sites interaction in which cationic or neutral Cu species (Cu2+ and CuHL0) coordinated with neutral amine sites and anionic complex species (CuL− and Cu2L22−) directly interacted with protonated amine sites via electrostatic attraction, and the ratio of the two interactions was approximately 0.5 for the equimolar bi-solutes system. Moreover, commonly coexisting ions in wastewaters had no obvious effect on the superior performance of PAMD. Also, Cu and CA could be recovered completely with HCl. Therefore, PAMD has a great potential to efficiently remove heavy metal ions from wastewaters in the presence of organic acids. PMID:25962970

  12. Multi-layer multi-configuration time-dependent Hartree (ML-MCTDH) approach to the correlated exciton-vibrational dynamics in the FMO complex

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

    Schulze, Jan; Kühn, Oliver, E-mail: oliver.kuehn@uni-rostock.de; Shibl, Mohamed F., E-mail: mfshibl@qu.edu.qa

    2016-05-14

    The coupled quantum dynamics of excitonic and vibrational degrees of freedom is investigated for high-dimensional models of the Fenna-Matthews-Olson complex. This includes a seven- and an eight-site model with 518 and 592 harmonic vibrational modes, respectively. The coupling between local electronic transitions and vibrations is described within the Huang-Rhys model using parameters that are obtained by discretization of an experimental spectral density. Different pathways of excitation energy flow are analyzed in terms of the reduced one-exciton density matrix, focussing on the role of vibrational and vibronic excitations. Distinct features due to both competing time scales of vibrational and exciton motionmore » and vibronically assisted transfer are observed. The question of the effect of initial state preparation is addressed by comparing the case of an instantaneous Franck-Condon excitation at a single site with that of a laser field excitation.« less

  13. A stable isotope approach for source apportionment of chlorinated ethene plumes at a complex multi-contamination events urban site

    NASA Astrophysics Data System (ADS)

    Nijenhuis, Ivonne; Schmidt, Marie; Pellegatti, Eleonora; Paramatti, Enrico; Richnow, Hans Hermann; Gargini, Alessandro

    2013-10-01

    The stable carbon isotope composition of chlorinated aliphatic compounds such as chlorinated methanes, ethanes and ethenes was examined as an intrinsic fingerprint for apportionment of sources. A complex field site located in Ferrara (Italy), with more than 50 years history of use of chlorinated aliphatic compounds, was investigated in order to assess contamination sources. Several contamination plumes were found in a complex alluvial sandy multi-aquifer system close to the river Po; sources are represented by uncontained former industrial and municipal dump sites as well as by spills at industrial areas. The carbon stable isotope signature allowed distinguishing 2 major sources of contaminants. One source of chlorinated aliphatic contaminants was strongly depleted in 13C (<-60‰) suggesting production lines which have used depleted methane for synthesis. The other source had typical carbon isotope compositions of >-40‰ which is commonly observed in recent production of chlorinated solvents. The degradation processes in the plumes could be traced interpreting the isotope enrichment and depletion of parent and daughter compounds, respectively. We demonstrate that, under specific production conditions, namely when highly chlorinated ethenes are produced as by-product during chloromethanes production, 13C depleted fingerprinting of contaminants can be obtained and this can be used to track sources and address the responsible party of the pollution in urban areas.

  14. A stable isotope approach for source apportionment of chlorinated ethene plumes at a complex multi-contamination events urban site.

    PubMed

    Nijenhuis, Ivonne; Schmidt, Marie; Pellegatti, Eleonora; Paramatti, Enrico; Richnow, Hans Hermann; Gargini, Alessandro

    2013-10-01

    The stable carbon isotope composition of chlorinated aliphatic compounds such as chlorinated methanes, ethanes and ethenes was examined as an intrinsic fingerprint for apportionment of sources. A complex field site located in Ferrara (Italy), with more than 50years history of use of chlorinated aliphatic compounds, was investigated in order to assess contamination sources. Several contamination plumes were found in a complex alluvial sandy multi-aquifer system close to the river Po; sources are represented by uncontained former industrial and municipal dump sites as well as by spills at industrial areas. The carbon stable isotope signature allowed distinguishing 2 major sources of contaminants. One source of chlorinated aliphatic contaminants was strongly depleted in ¹³C (<-60‰) suggesting production lines which have used depleted methane for synthesis. The other source had typical carbon isotope compositions of >-40‰ which is commonly observed in recent production of chlorinated solvents. The degradation processes in the plumes could be traced interpreting the isotope enrichment and depletion of parent and daughter compounds, respectively. We demonstrate that, under specific production conditions, namely when highly chlorinated ethenes are produced as by-product during chloromethanes production, ¹³C depleted fingerprinting of contaminants can be obtained and this can be used to track sources and address the responsible party of the pollution in urban areas. © 2013 Elsevier B.V. All rights reserved.

  15. Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

    PubMed

    Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

    2015-07-10

    Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

  16. 14 CFR 417.405 - Ground safety analysis.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... qualified to perform the ground safety analysis through training, education, and experience. (c) A launch... unfenced boundary of an entire industrial complex or multi-user launch site. A launch location hazard may.... (j) A launch operator must verify all information in a ground safety analysis, including design...

  17. 14 CFR 417.405 - Ground safety analysis.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... qualified to perform the ground safety analysis through training, education, and experience. (c) A launch... unfenced boundary of an entire industrial complex or multi-user launch site. A launch location hazard may.... (j) A launch operator must verify all information in a ground safety analysis, including design...

  18. 14 CFR 417.405 - Ground safety analysis.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... qualified to perform the ground safety analysis through training, education, and experience. (c) A launch... unfenced boundary of an entire industrial complex or multi-user launch site. A launch location hazard may.... (j) A launch operator must verify all information in a ground safety analysis, including design...

  19. Prediction accuracies for growth and wood attributes of interior spruce in space using genotyping-by-sequencing.

    PubMed

    Gamal El-Dien, Omnia; Ratcliffe, Blaise; Klápště, Jaroslav; Chen, Charles; Porth, Ilga; El-Kassaby, Yousry A

    2015-05-09

    Genomic selection (GS) in forestry can substantially reduce the length of breeding cycle and increase gain per unit time through early selection and greater selection intensity, particularly for traits of low heritability and late expression. Affordable next-generation sequencing technologies made it possible to genotype large numbers of trees at a reasonable cost. Genotyping-by-sequencing was used to genotype 1,126 Interior spruce trees representing 25 open-pollinated families planted over three sites in British Columbia, Canada. Four imputation algorithms were compared (mean value (MI), singular value decomposition (SVD), expectation maximization (EM), and a newly derived, family-based k-nearest neighbor (kNN-Fam)). Trees were phenotyped for several yield and wood attributes. Single- and multi-site GS prediction models were developed using the Ridge Regression Best Linear Unbiased Predictor (RR-BLUP) and the Generalized Ridge Regression (GRR) to test different assumption about trait architecture. Finally, using PCA, multi-trait GS prediction models were developed. The EM and kNN-Fam imputation methods were superior for 30 and 60% missing data, respectively. The RR-BLUP GS prediction model produced better accuracies than the GRR indicating that the genetic architecture for these traits is complex. GS prediction accuracies for multi-site were high and better than those of single-sites while multi-site predictability produced the lowest accuracies reflecting type-b genetic correlations and deemed unreliable. The incorporation of genomic information in quantitative genetics analyses produced more realistic heritability estimates as half-sib pedigree tended to inflate the additive genetic variance and subsequently both heritability and gain estimates. Principle component scores as representatives of multi-trait GS prediction models produced surprising results where negatively correlated traits could be concurrently selected for using PCA2 and PCA3. The application of GS to open-pollinated family testing, the simplest form of tree improvement evaluation methods, was proven to be effective. Prediction accuracies obtained for all traits greatly support the integration of GS in tree breeding. While the within-site GS prediction accuracies were high, the results clearly indicate that single-site GS models ability to predict other sites are unreliable supporting the utilization of multi-site approach. Principle component scores provided an opportunity for the concurrent selection of traits with different phenotypic optima.

  20. CliniProteus: A flexible clinical trials information management system

    PubMed Central

    Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael

    2007-01-01

    Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment. Availability http://www.rfdn.org/bioinfo/CTMS/ctms.html. PMID:21670796

  1. On Complex Nuclei Energetics in LENR

    NASA Astrophysics Data System (ADS)

    Miley, George H.; Hora, Heinz

    2005-03-01

    Swimming Electron Layer (SEL) theory plus fission of ``complex nuclei'' were proposed earlier to explain reaction products observed in electrolysis with multi-layer thin-film metallic electrodesootnotetext1.G.H. Miley, and J.A. Patterson, J. New Energy, Vol. 1, pp.11-15, (1996).. SEL was then extended to treat gas-diffusion driven transmutation experimentsootnotetextG. H. Miley and H. Hora, ``Nuclear Reactions in Solids,'' APS DNP Mtg., East Lansing, MI, Oct (2002).. It is also consistent with measured charged-particle emission during thin-film electrolysis and x-ray emission during plasma bombardment experimentsootnotetextA. Karabut, ``X-ray emission in high-current glow discharge,'' Proc., ICCF-9, Beijing China, May (2002).. The binding energy per complex nucleon can be estimated by an energy balance combined with identification of products for each complex e.g. complexes of A 39 have ˜ 0.05 MeV/Nucleon, etc, in thin film electrolysis. Energies in gas diffusion experiments are lower due to the reduced trap site potential at the multi-atom surface. In the case of x-ray emission, complexes involve subsurface defect center traps, giving only a few keV/Nucleon, consistent with experiments^3.

  2. Multiscale characterization and mechanical modeling of an Al-Zn-Mg electron beam weld

    NASA Astrophysics Data System (ADS)

    Puydt, Quentin; Flouriot, Sylvain; Ringeval, Sylvain; Parry, Guillaume; De Geuser, Frédéric; Deschamps, Alexis

    Welding of precipitation hardening alloys results in multi-scale microstructural heterogeneities, from the hardening nano-scale precipitates to the micron-scale solidification structures and to the component geometry. This heterogeneity results in a complex mechanical response, with gradients in strength, stress triaxiality and damage initiation sites.

  3. Large area sub-micron chemical imaging of magnesium in sea urchin teeth.

    PubMed

    Masic, Admir; Weaver, James C

    2015-03-01

    The heterogeneous and site-specific incorporation of inorganic ions can profoundly influence the local mechanical properties of damage tolerant biological composites. Using the sea urchin tooth as a research model, we describe a multi-technique approach to spatially map the distribution of magnesium in this complex multiphase system. Through the combined use of 16-bit backscattered scanning electron microscopy, multi-channel energy dispersive spectroscopy elemental mapping, and diffraction-limited confocal Raman spectroscopy, we demonstrate a new set of high throughput, multi-spectral, high resolution methods for the large scale characterization of mineralized biological materials. In addition, instrument hardware and data collection protocols can be modified such that several of these measurements can be performed on irregularly shaped samples with complex surface geometries and without the need for extensive sample preparation. Using these approaches, in conjunction with whole animal micro-computed tomography studies, we have been able to spatially resolve micron and sub-micron structural features across macroscopic length scales on entire urchin tooth cross-sections and correlate these complex morphological features with local variability in elemental composition. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Contaminant source and release history identification in groundwater: A multi-step approach

    NASA Astrophysics Data System (ADS)

    Gzyl, G.; Zanini, A.; Frączek, R.; Kura, K.

    2014-02-01

    The paper presents a new multi-step approach aiming at source identification and release history estimation. The new approach consists of three steps: performing integral pumping tests, identifying sources, and recovering the release history by means of a geostatistical approach. The present paper shows the results obtained from the application of the approach within a complex case study in Poland in which several areal sources were identified. The investigated site is situated in the vicinity of a former chemical plant in southern Poland in the city of Jaworzno in the valley of the Wąwolnica River; the plant has been in operation since the First World War producing various chemicals. From an environmental point of view the most relevant activity was the production of pesticides, especially lindane. The application of the multi-step approach enabled a significant increase in the knowledge of contamination at the site. Some suspected contamination sources have been proven to have minor effect on the overall contamination. Other suspected sources have been proven to have key significance. Some areas not taken into consideration previously have now been identified as key sources. The method also enabled estimation of the magnitude of the sources and, a list of the priority reclamation actions will be drawn as a result. The multi-step approach has proven to be effective and may be applied to other complicated contamination cases. Moreover, the paper shows the capability of the geostatistical approach to manage a complex real case study.

  5. Crystallization of Mitochondrial Respiratory Complex II from Chicken Heart: a Membrane Protein Complex Diffracting to 2.0 Å.

    PubMed Central

    Huang, Li-shar; Borders, Toni M.; Shen, John T.; Wang, Chung-Jen; Berry, Edward

    2006-01-01

    Synopsis A multi-subunit mitochondrial membrane protein complex involved in the Krebs Cycle and respiratory chain has been crystallized in a form suitable for near-atomic resolution structure determination. A procedure is presented for preparation of diffraction-quality crystals of a vertebrate mitochondrial respiratory Complex II. The crystals have the potential to diffract to at least 2.0 Å with optimization of post-crystal-growth treatment and cryoprotection. This should allow determination of the structure of this important and medically relevant membrane protein complex at near-atomic resolution and provide great detail of the mode of binding of substrates and inhibitors at the two substrate-binding sites. PMID:15805592

  6. KSC-99pp1257

    NASA Image and Video Library

    1999-10-29

    The first roof panels are placed on the multi-purpose hangar at the site of the $8 million Reusable Launch Vehicle (RLV) Support Complex at Kennedy Space Center. The RLV complex, which includes the hangar and a building for related ground support equipment and administrative/technical support, will be available to accommodate the Space Shuttle; the X-34 RLV technology demonstrator; the L-1011 carrier aircraft for Pegasus and X-34; and other RLV and X-vehicle programs. The complex is jointly funded by the Spaceport Florida Authority, NASA's Space Shuttle Program and KSC. The facility will be operational in early 2000

  7. KSC-99pp1259

    NASA Image and Video Library

    1999-10-29

    Work continues on construction of the multi-purpose hangar at the site of the $8 million Reusable Launch Vehicle (RLV) Support Complex at Kennedy Space Center. In the background can be seen the new construction for the building that will house related ground support equipment and administrative/technical support. The RLV complex will be available to accommodate the Space Shuttle; the X-34 RLV technology demonstrator; the L-1011 carrier aircraft for Pegasus and X-34; and other RLV and X-vehicle programs. The complex is jointly funded by the Spaceport Florida Authority, NASA's Space Shuttle Program and KSC. The facility will be operational in early 2000

  8. KSC-99pp1262

    NASA Image and Video Library

    1999-10-29

    Workers place the first roof panels on the multi-purpose hangar at the site of the $8 million Reusable Launch Vehicle (RLV) Support Complex at Kennedy Space Center. The RLV complex, which includes the hangar and a building for related ground support equipment and administrative/technical support, will be available to accommodate the Space Shuttle; the X-34 RLV technology demonstrator; the L-1011 carrier aircraft for Pegasus and X-34; and other RLV and X-vehicle programs. The complex is jointly funded by the Spaceport Florida Authority, NASA's Space Shuttle Program and KSC. The facility will be operational in early 2000

  9. What is the benefit of driving a hydrological model with data from a multi-site weather generator compared to data from a simple delta change approach?"

    NASA Astrophysics Data System (ADS)

    Rössler, Ole; Keller, Denise; Fischer, Andreas

    2016-04-01

    In 2011 the Swiss national consortium C2SM providednew climate change scenarios were released in Switzerland that came with a comprehensive data set of temperature and precipitation changes under climate change conditions for every a large network of meteorological stations, and for aggregated as well as regions in across Switzerland. These climate change signals were generated for three emission scenarios and three different future time-periods and designed to be used asbased on a delta change factors approach. This data set proved to be very successful in Switzerland as many different users, researchers, private companies, and societal users were able to use and interpret the climate data set. Thus, a range of applications that are all based on the same climate data set enabled a comparable view on climate change impact in several disciplines. The main limitation and criticism to this data set was the usage of the delta change approach for downscaling as it comes with severe limitations such as underestimatinges changes in extreme values and neglecting changes in variability and changes in temporal sequencesneglecting changes in variability, be it year-to-year or day-to-day, and changes in temporal sequences . lacks a change in the day-to-day-variability. One way to overcome this the latter limitation is the usage of stochastic weather generators in a downscaling context. Weather generators are known to be one suitable downscaling technique, but A common limitation of most weather generators is the absence of spatial consistency rrelation in the generated daily time-series, resulting in an underestimation of areal means over several stations that are often low-biased. refer to one point scale (single-site) and lacks the spatial representation of weather. The latter A realistic representation of the inter-station correlation in the downscaled time-series This is of high particular importance in some impact studies, especially infor any hydrological impact studiesy. Recently, a multi-site weather generator was developed and tested for downscaling purposes over Switzerland. The weather generator is of type Richardson, that is run with spatially correlated random number streams to ensure spatial consistency. As a downside, multi-site weather generators are much more complex to develop, but they are a very promising alternative downscaling technique. A new multi-site-weather generator was developed for Switzerland in a previous study (Keller et al. 2014). In this study, we tested this new multi-site-weather generator against the "standard" delta change derived data in a hydrological impact assessment study that focused on runoff in the meso-scale catchment of the river Thur catchment. Two hydrological models of different complexity were run with the data sets under present (1980-2009) and under future conditions (2070-2099), assuming the SRES A1B emission2070-2100 scenario conditions. Eight meteorological stations were used to interpolate a meteorological field that served as input to calibrate and validate the two hydrological models against runoff. The downscaling intercomparison was done for We applied 10 GCM-RCM combinations simulations of the ENSEMBLES. In case of the weather generator, that allows for multiple synthetic realizations, we generated for which change factors for each station (delta change approach) were available and generated 25 realizations of multi-site weather. with each climate model projection. Results show that the delta change driven data constitutes only one appropriate representation compared to theof a bandwidth of runoff projections yielded by the multi-site weather generator data. Especially oOn average, differences between both the two approaches are small. Low and high runoff Runoff values to both extremes are however better reproduced with the weather generator driven data set. The stochastic representation of multiday rainfall events are considered as the main reason. Hence, tThere is a clear yet small added value to the delta change approach that in turn performs rather well. Although these small but considerable differences might questioning the need to construct a multi-site-weather generator with a huge effort, the potential and possibilities to further develop the multi-site weather generator is undoubted.

  10. Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency☆

    PubMed Central

    Simon, Mariella T.; Ng, Bobby G.; Friederich, Marisa W.; Wang, Raymond Y.; Boyer, Monica; Kircher, Martin; Collard, Renata; Buckingham, Kati J.; Chang, Richard; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Van Hove, Johan L.K.; Freeze, Hudson H.; Abdenur, Jose E.

    2017-01-01

    We report the clinical, biochemical, and molecular findings in two brothers with encephalopathy and multi-systemic disease. Abnormal transferrin glycoforms were suggestive of a type I congenital disorder of glycosylation (CDG). While exome sequencing was negative for CDG related candidate genes, the testing revealed compound heterozygous mutations in the mitochondrial elongation factor G gene (GFM1). One of the mutations had been reported previously while the second, novel variant was found deep in intron 6, activating a cryptic splice site. Functional studies demonstrated decreased GFM1 protein levels, suggested disrupted assembly of mitochondrial complexes III and V and decreased activities of mitochondrial complexes I and IV, all indicating combined OXPHOS deficiency. PMID:28216230

  11. RIPiT-Seq: A high-throughput approach for footprinting RNA:protein complexes

    PubMed Central

    Singh, Guramrit; Ricci, Emiliano P.; Moore, Melissa J.

    2013-01-01

    Development of high-throughput approaches to map the RNA interaction sites of individual RNA binding proteins (RBPs) transcriptome-wide is rapidly transforming our understanding of post-transcriptional gene regulatory mechanisms. Here we describe a ribonucleoprotein (RNP) footprinting approach we recently developed for identifying occupancy sites of both individual RBPs and multi-subunit RNP complexes. RNA:protein immunoprecipitation in tandem (RIPiT) yields highly specific RNA footprints of cellular RNPs isolated via two sequential purifications; the resulting RNA footprints can then be identified by high-throughput sequencing (Seq). RIPiT-Seq is broadly applicable to all RBPs regardless of their RNA binding mode and thus provides a means to map the RNA binding sites of RBPs with poor inherent ultraviolet (UV) crosslinkability. Further, among current high-throughput approaches, RIPiT has the unique capacity to differentiate binding sites of RNPs with overlapping protein composition. It is therefore particularly suited for studying dynamic RNP assemblages whose composition evolves as gene expression proceeds. PMID:24096052

  12. The GH51 α-l-arabinofuranosidase from Paenibacillus sp. THS1 is multifunctional, hydrolyzing main-chain and side-chain glycosidic bonds in heteroxylans.

    PubMed

    Bouraoui, Hanen; Desrousseaux, Marie-Laure; Ioannou, Eleni; Alvira, Pablo; Manaï, Mohamed; Rémond, Caroline; Dumon, Claire; Fernandez-Fuentes, Narcis; O'Donohue, Michael J

    2016-01-01

    Conceptually, multi-functional enzymes are attractive because in the case of complex polymer hydrolysis having two or more activities defined by a single enzyme offers the possibility of synergy and reduced enzyme cocktail complexity. Nevertheless, multi-functional enzymes are quite rare and are generally multi-domain assemblies with each activity being defined by a separate protein module. However, a recent report described a GH51 arabinofuranosidase from Alicyclobacillus sp. A4 that displays both α-l-arabinofuranosidase and β-d-xylanase activities, which are defined by a single active site. Following on from this, we describe in detail another multi-functional GH51 arabinofuranosidase and discuss the molecular basis of multifunctionality. THSAbf is a GH51 α-l-arabinofuranosidase. Characterization revealed that THSAbf is active up to 75 °C, stable at 60 °C and active over a broad pH range (4-7). THSAbf preferentially releases para-nitrophenyl from the l-arabinofuranoside (k cat/K M = 1050 s(-1) mM(-1)) and to some extent from d-galactofuranoside and d-xyloside. THSAbf is active on 4-O-methylglucuronoxylans from birch and beechwood (10.8 and 14.4 U mg(-1), respectively) and on sugar beet branched and linear arabinans (1.1 ± 0.24 and 1.8 ± 0.1 U mg(-1)). Further investigation revealed that like the Alicyclobacillus sp. A4 α-l-arabinofuranosidase, THSAbf also displays endo-xylanase activity, cleaving β-1,4 bonds in heteroxylans. The optimum pH for THASAbf activity is substrate dependent, but ablation of the catalytic nucleophile caused a general loss of activity, indicating the involvement of a single active center. Combining the α-l-arabinofuranosidase with a GH11 endoxylanase did not procure synergy. The molecular modeling of THSAbf revealed a wide active site cleft and clues to explain multi-functionality. The discovery of single active site, multifunctional enzymes such as THSAbf opens up exciting avenues for enzyme engineering and the development of new biomass-degrading cocktails that could considerably reduce enzyme production costs.

  13. Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions

    NASA Astrophysics Data System (ADS)

    Manzi, Lucio; Barrow, Andrew S.; Scott, Daniel; Layfield, Robert; Wright, Timothy G.; Moses, John E.; Oldham, Neil J.

    2016-11-01

    Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

  14. Coastal flooding as a parameter in multi-criteria analysis for industrial site selection

    NASA Astrophysics Data System (ADS)

    Christina, C.; Memos, C.; Diakoulaki, D.

    2014-12-01

    Natural hazards can trigger major industrial accidents, which apart from affecting industrial installations may cause a series of accidents with serious impacts on human health and the environment far beyond the site boundary. Such accidents, also called Na-Tech (natural - technical) accidents, deserve particular attention since they can cause release of hazardous substances possibly resulting in severe environmental pollution, explosions and/or fires. There are different kinds of natural events or, in general terms, of natural causes of industrial accidents, such as landslides, hurricanes, high winds, tsunamis, lightning, cold/hot temperature, floods, heavy rains etc that have caused accidents. The scope of this paper is to examine the coastal flooding as a parameter in causing an industrial accident, such as the nuclear disaster in Fukushima, Japan, and the critical role of this parameter in industrial site selection. Land use planning is a complex procedure that requires multi-criteria decision analysis involving economic, environmental and social parameters. In this context the parameter of a natural hazard occurrence, such as coastal flooding, for industrial site selection should be set by the decision makers. In this paper it is evaluated the influence that has in the outcome of a multi-criteria decision analysis for industrial spatial planning the parameter of an accident risk triggered by coastal flooding. The latter is analyzed in the context of both sea-and-inland induced flooding.

  15. Field Trials of the Multi-Source Approach for Resistivity and Induced Polarization Data Acquisition

    NASA Astrophysics Data System (ADS)

    LaBrecque, D. J.; Morelli, G.; Fischanger, F.; Lamoureux, P.; Brigham, R.

    2013-12-01

    Implementing systems of distributed receivers and transmitters for resistivity and induced polarization data is an almost inevitable result of the availability of wireless data communication modules and GPS modules offering precise timing and instrument locations. Such systems have a number of advantages; for example, they can be deployed around obstacles such as rivers, canyons, or mountains which would be difficult with traditional 'hard-wired' systems. However, deploying a system of identical, small, battery powered, transceivers, each capable of injecting a known current and measuring the induced potential has an additional and less obvious advantage in that multiple units can inject current simultaneously. The original purpose for using multiple simultaneous current sources (multi-source) was to increase signal levels. In traditional systems, to double the received signal you inject twice the current which requires you to apply twice the voltage and thus four times the power. Alternatively, one approach to increasing signal levels for large-scale surveys collected using small, battery powered transceivers is it to allow multiple units to transmit in parallel. In theory, using four 400 watt transmitters on separate, parallel dipoles yields roughly the same signal as a single 6400 watt transmitter. Furthermore, implementing the multi-source approach creates the opportunity to apply more complex current flow patterns than simple, parallel dipoles. For a perfect, noise-free system, multi-sources adds no new information to a data set that contains a comprehensive set of data collected using single sources. However, for realistic, noisy systems, it appears that multi-source data can substantially impact survey results. In preliminary model studies, the multi-source data produced such startling improvements in subsurface images that even the authors questioned their veracity. Between December of 2012 and July of 2013, we completed multi-source surveys at five sites with depths of exploration ranging from 150 to 450 m. The sites included shallow geothermal sites near Reno Nevada, Pomarance Italy, and Volterra Italy; a mineral exploration site near Timmins Quebec; and a landslide investigation near Vajont Dam in northern Italy. These sites provided a series of challenges in survey design and deployment including some extremely difficult terrain and a broad range of background resistivity and induced values. Despite these challenges, comparison of multi-source results to resistivity and induced polarization data collection with more traditional methods support the thesis that the multi-source approach is capable of providing substantial improvements in both depth of penetration and resolution over conventional approaches.

  16. Excited state electron and energy relays in supramolecular dinuclear complexes revealed by ultrafast optical and X-ray transient absorption spectroscopy.

    PubMed

    Hayes, Dugan; Kohler, Lars; Hadt, Ryan G; Zhang, Xiaoyi; Liu, Cunming; Mulfort, Karen L; Chen, Lin X

    2018-01-28

    The kinetics of photoinduced electron and energy transfer in a family of tetrapyridophenazine-bridged heteroleptic homo- and heterodinuclear copper(i) bis(phenanthroline)/ruthenium(ii) polypyridyl complexes were studied using ultrafast optical and multi-edge X-ray transient absorption spectroscopies. This work combines the synthesis of heterodinuclear Cu(i)-Ru(ii) analogs of the homodinuclear Cu(i)-Cu(i) targets with spectroscopic analysis and electronic structure calculations to first disentangle the dynamics at individual metal sites by taking advantage of the element and site specificity of X-ray absorption and theoretical methods. The excited state dynamical models developed for the heterodinuclear complexes are then applied to model the more challenging homodinuclear complexes. These results suggest that both intermetallic charge and energy transfer can be observed in an asymmetric dinuclear copper complex in which the ground state redox potentials of the copper sites are offset by only 310 meV. We also demonstrate the ability of several of these complexes to effectively and unidirectionally shuttle energy between different metal centers, a property that could be of great use in the design of broadly absorbing and multifunctional multimetallic photocatalysts. This work provides an important step toward developing both a fundamental conceptual picture and a practical experimental handle with which synthetic chemists, spectroscopists, and theoreticians may collaborate to engineer cheap and efficient photocatalytic materials capable of performing coulombically demanding chemical transformations.

  17. Where to Settle—Settlement Preferences of Mytilus galloprovincialis and Choice of Habitat at a Micro Spatial Scale

    PubMed Central

    Carl, Christina; Poole, Andrew J.; Williams, Mike R.; de Nys, Rocky

    2012-01-01

    The global mussel aquaculture industry uses specialised spat catching and nursery culture ropes made of multi-filament synthetic and natural fibres to optimise settlement and retention of mussels for on-growing. However, the settlement ecology and preferences of mussels are poorly understood and only sparse information exists in a commercial context. This study quantified the settlement preferences of pediveligers and plantigrades of Mytilus galloprovincialis on increasingly complex surfaces and settlement locations at a micro spatial scale on and within ropes under commercial hatchery operating conditions using optical microscopy and X-ray micro-computed tomography (µCT). M. galloprovincialis has clear settlement preferences for more complex materials and high selectivity for settlement sites from the pediveliger through to the plantigrade stage. Pediveligers of M. galloprovincialis initially settle inside specialised culture ropes. Larger pediveligers were located close to the exterior of ropes as they increased in size over time. In contrast, smaller individuals were located deeper inside of the ropes over time. This study demonstrates that X-ray µCT is an excellent non-destructive technique for mapping settlement and attachment sites of individuals as early as one day post settlement, and quantifies the number and location of settled individuals on and within ropes as a tool to understand and optimise settlement in complex multi-dimensional materials and environments. PMID:23251710

  18. How Can Multi-Site Evaluations Be Participatory?

    ERIC Educational Resources Information Center

    Lawrenz, Frances; Huffman, Douglas

    2003-01-01

    Multi-site evaluations are becoming increasingly common in federal funding portfolios. Although much thought has been given to multi-site evaluation, there has been little emphasis on how it might interact with participatory evaluation. Therefore, this paper reviews several National Science Foundation educational, multi-site evaluations for the…

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

    Zayas, Jose; Derby, Mike; Ralston, Kiersten

    Atmosphere to Electrons (A2e) is a multi-year U.S. Department of Energy (DOE) research initiative targeting significant reductions in the cost of wind energy through an improved understanding of the complex physics governing electricity generation by wind plants. The goal of A2e is to ensure future wind plants are sited, built, and operated in a way that produces the most cost-effective, usable electric power.

  20. Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.

    PubMed

    Burkova, Evgeniya E; Dmitrenok, Pavel S; Sedykh, Sergey E; Buneva, Valentina N; Soboleva, Svetlana E; Nevinsky, Georgy A

    2014-01-01

    Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼ 1000 kDa) from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs) 4-14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa) as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions.

  1. Evaluation of a multi-site program designed to strengthen relational bonds for siblings separated by foster care.

    PubMed

    Waid, Jeffrey; Wojciak, Armeda Stevenson

    2017-10-01

    Sibling relationships in foster care settings have received increased attention in recent years. Despite growing evidence regarding the protective potential of sibling relationships for youth in care, some sibling groups continue to experience foster care related separation, and few programs exist to address the needs of these youth. This study describes and evaluates Camp To Belong, a multi-site program designed to provide short-term reunification to separated sibling groups through a week-long summer camp experience. Using a pre-test post-test survey design, this paper examines changes in youth ratings of sibling conflict and sibling support across camps located in six geographically distinct regions of the United States. The effects of youth age, number of prior camp exposures, and camp location were tested using multilevel modeling procedures. Findings suggest that participation in Camp To Belong may reduce sibling conflict, and improvements in sibling support are noted for youth who have had prior exposure to the camp's programming. Camp-level variance in the sibling support outcome highlight the complex nature of relationships for siblings separated by foster care, and suggest the need for additional research. Lessons learned from this multi-site evaluation and future directions are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. SU-F-T-312: Identifying Distinct Radiation Therapy Plan Classes Through Multi-Dimensional Analysis of Plan Complexity Metrics

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

    Desai, V; Labby, Z; Culberson, W

    Purpose: To determine whether body site-specific treatment plans form unique “plan class” clusters in a multi-dimensional analysis of plan complexity metrics such that a single beam quality correction determined for a representative plan could be universally applied within the “plan class”, thereby increasing the dosimetric accuracy of a detector’s response within a subset of similarly modulated nonstandard deliveries. Methods: We collected 95 clinical volumetric modulated arc therapy (VMAT) plans from four body sites (brain, lung, prostate, and spine). The lung data was further subdivided into SBRT and non-SBRT data for a total of five plan classes. For each control pointmore » in each plan, a variety of aperture-based complexity metrics were calculated and stored as unique characteristics of each patient plan. A multiple comparison of means analysis was performed such that every plan class was compared to every other plan class for every complexity metric in order to determine which groups could be considered different from one another. Statistical significance was assessed after correcting for multiple hypothesis testing. Results: Six out of a possible 10 pairwise plan class comparisons were uniquely distinguished based on at least nine out of 14 of the proposed metrics (Brain/Lung, Brain/SBRT lung, Lung/Prostate, Lung/SBRT Lung, Lung/Spine, Prostate/SBRT Lung). Eight out of 14 of the complexity metrics could distinguish at least six out of the possible 10 pairwise plan class comparisons. Conclusion: Aperture-based complexity metrics could prove to be useful tools to quantitatively describe a distinct class of treatment plans. Certain plan-averaged complexity metrics could be considered unique characteristics of a particular plan. A new approach to generating plan-class specific reference (pcsr) fields could be established through a targeted preservation of select complexity metrics or a clustering algorithm that identifies plans exhibiting similar modulation characteristics. Measurements and simulations will better elucidate potential plan-class specific dosimetry correction factors.« less

  3. Multi-Cohort Stand Structural Classification: Ground- and LiDAR-based Approaches for Boreal Mixedwood and Black Spruce Forest Types of Northeastern Ontario

    NASA Astrophysics Data System (ADS)

    Kuttner, Benjamin George

    Natural fire return intervals are relatively long in eastern Canadian boreal forests and often allow for the development of stands with multiple, successive cohorts of trees. Multi-cohort forest management (MCM) provides a strategy to maintain such multi-cohort stands that focuses on three broad phases of increasingly complex, post-fire stand development, termed "cohorts", and recommends different silvicultural approaches be applied to emulate different cohort types. Previous research on structural cohort typing has relied upon primarily subjective classification methods; in this thesis, I develop more comprehensive and objective methods for three common boreal mixedwood and black spruce forest types in northeastern Ontario. Additionally, I examine relationships between cohort types and stand age, productivity, and disturbance history and the utility of airborne LiDAR to retrieve ground-based classifications and to extend structural cohort typing from plot- to stand-levels. In both mixedwood and black spruce forest types, stand age and age-related deadwood features varied systematically with cohort classes in support of an age-based interpretation of increasing cohort complexity. However, correlations of stand age with cohort classes were surprisingly weak. Differences in site productivity had a significant effect on the accrual of increasingly complex multi-cohort stand structure in both forest types, especially in black spruce stands. The effects of past harvesting in predictive models of class membership were only significant when considered in isolation of age. As an age-emulation strategy, the three cohort model appeared to be poorly suited to black spruce forests where the accrual of structural complexity appeared to be more a function of site productivity than age. Airborne LiDAR data appear to be particularly useful in recovering plot-based cohort types and extending them to the stand-level. The main gradients of structural variability detected using LiDAR were similar between boreal mixedwood and black spruce forest types; the best LiDAR-based models of cohort type relied upon combinations of tree size, size heterogeneity, and tree density related variables. The methods described here to measure, classify, and predict cohort-related structural complexity assist in translating the conceptual three cohort model to a more precise, measurement-based management system. In addition, the approaches presented here to measure and classify stand structural complexity promise to significantly enhance the detail of structural information in operational forest inventories in support of a wide array of forest management and conservation applications.

  4. On multi-site damage identification using single-site training data

    NASA Astrophysics Data System (ADS)

    Barthorpe, R. J.; Manson, G.; Worden, K.

    2017-11-01

    This paper proposes a methodology for developing multi-site damage location systems for engineering structures that can be trained using single-site damaged state data only. The methodology involves training a sequence of binary classifiers based upon single-site damage data and combining the developed classifiers into a robust multi-class damage locator. In this way, the multi-site damage identification problem may be decomposed into a sequence of binary decisions. In this paper Support Vector Classifiers are adopted as the means of making these binary decisions. The proposed methodology represents an advancement on the state of the art in the field of multi-site damage identification which require either: (1) full damaged state data from single- and multi-site damage cases or (2) the development of a physics-based model to make multi-site model predictions. The potential benefit of the proposed methodology is that a significantly reduced number of recorded damage states may be required in order to train a multi-site damage locator without recourse to physics-based model predictions. In this paper it is first demonstrated that Support Vector Classification represents an appropriate approach to the multi-site damage location problem, with methods for combining binary classifiers discussed. Next, the proposed methodology is demonstrated and evaluated through application to a real engineering structure - a Piper Tomahawk trainer aircraft wing - with its performance compared to classifiers trained using the full damaged-state dataset.

  5. PS2-06: Best Practices for Advancing Multi-site Chart Abstraction Research

    PubMed Central

    Blick, Noelle; Cole, Deanna; King, Colleen; Riordan, Rick; Von Worley, Ann; Yarbro, Patty

    2012-01-01

    Background/Aims Multi-site chart abstraction studies are becoming increasingly common within the HMORN. Differences in systems among HMORN sites can pose significant obstacles to the success of these studies. It is therefore crucial to standardize abstraction activities by following best practices for multi-site chart abstraction, as consistency of processes across sites will increase efficiencies and enhance data quality. Methods Over the past few months the authors have been meeting to identify obstacles to multi-site chart abstraction and to address ways in which multi-site chart abstraction processes can be systemized and standardized. The aim of this workgroup is to create a best practice guide for multi-site chart abstraction studies. Focus areas include: abstractor training, format for chart abstraction (database, paper, etc), data quality, redaction, mechanism for transferring data, site specific access to medical records, IRB/HIPAA concerns, and budgetary issues. Results The results of the workgroup’s efforts (the best practice guide) will be presented by a panel of experts at the 2012 HMORN conference. The presentation format will also focus on discussion among attendees to elicit further input and to identify areas that need to be further addressed. Subsequently, the best practice guide will be posted on the HMORN website. Discussion The best practice guide for multi-site chart abstraction studies will establish sound guidelines and serve as an aid to researchers embarking on multi-site chart abstraction studies. Efficiencies and data quality will be further enhanced with standardized multi-site chart abstraction practices.

  6. Quantifying climate changes of the Common Era for Finland

    NASA Astrophysics Data System (ADS)

    Luoto, Tomi P.; Nevalainen, Liisa

    2017-10-01

    In this study, we aim to quantify summer air temperatures from sediment records from Southern, Central and Northern Finland over the past 2000 years. We use lake sediment archives to estimate paleotemperatures applying fossil Chironomidae assemblages and the transfer function approach. The used enhanced Chironomidae-based temperature calibration set was validated in a 70-year high-resolution sediment record against instrumentally measured temperatures. Since the inferred and observed temperatures showed close correlation, we deduced that the new calibration model is reliable for reconstructions beyond the monitoring records. The 700-year long temperature reconstructions from three sites at multi-decadal temporal resolution showed similar trends, although they had differences in timing of the cold Little Ice Age (LIA) and the initiation of recent warming. The 2000-year multi-centennial reconstructions from three different sites showed resemblance with each other having clear signals of the Medieval Climate Anomaly (MCA) and LIA, but with differences in their timing. The influence of external forcing on climate of the southern and central sites appeared to be complex at the decadal scale, but the North Atlantic Oscillation (NAO) was closely linked to the temperature development of the northern site. Solar activity appears to be synchronous with the temperature fluctuations at the multi-centennial scale in all the sites. The present study provides new insights into centennial and decadal variability in air temperature dynamics in Northern Europe and on the external forcing behind these trends. These results are particularly useful in comparing regional responses and lags of temperature trends between different parts of Scandinavia.

  7. Correlation between lifetime heterogeneity and kinetics heterogeneity during chlorophyll fluorescence induction in leaves: 2. Multi-frequency phase and modulation analysis evidences a loosely connected PSII pigment-protein complex.

    PubMed

    Moise, Nicolae; Moya, Ismaël

    2004-06-28

    We report the first direct decomposition of the fluorescence lifetime heterogeneity during multiphasic fluorescence induction in dark-adapted leaves by multi-frequency phase and modulation fluorometry (PMF). A very fast component, assigned to photosystem I (PSI), was found to be constant in lifetime and yield, whereas the two slow components, which are strongly affected by the closure of the reaction centers by light, were assigned to PSII. Based on a modified "reversible radical pair" kinetic model with three compartments, we showed that a loosely connected pigment complex, which is assumed to be the CP47 complex, plays a specific role with respect to the structure and function of the PSII: (i) it explains the heterogeneity of PSII fluorescence lifetime as a compartmentation of excitation energy in the antenna, (ii) it is the site of a conformational change in the first second of illumination, and (iii) it is involved in the mechanisms of nonphotochemical quenching (NPQ). On the basis of the multi-frequency PMF analysis, we reconciled two apparently antagonistic aspects of chlorophyll a fluorescence in vivo: it is heterogeneous with respect to the kinetic structure (several lifetime components) and homogeneous with respect to average quantities (quasi-linear mean tau-Phi relationship).

  8. TROPHI: development of a tool to measure complex, multi-factorial patient handling interventions.

    PubMed

    Fray, Mike; Hignett, Sue

    2013-01-01

    Patient handling interventions are complex and multi-factorial. It has been difficult to make comparisons across different strategies due to the lack of a comprehensive outcome measurement method. The Tool for Risk Outstanding in Patient Handling Interventions (TROPHI) was developed to address this gap by measuring outcomes and comparing performance across interventions. Focus groups were held with expert patient handling practitioners (n = 36) in four European countries (Finland, Italy, Portugal and the UK) to identify preferred outcomes to be measured for interventions. A systematic literature review identified 598 outcome measures; these were critically appraised and the most appropriate measurement tool was selected for each outcome. TROPHI was evaluated in the four EU countries (eight sites) and by an expert panel (n = 16) from the European Panel of Patient Handling Ergonomics for usability and practical application. This final stage added external validity to the research by exploring transferability potential and presenting the data and analysis to allow respondent (participant) validation. Patient handling interventions are complex and multi-factorial and it has been difficult to make comparisons due to the lack of a comprehensive outcome measurement method. The Tool for Risk Outstanding in Patient Handling Interventions (TROPHI) was developed to address this gap by measuring outcomes to compare performance across interventions.

  9. The Geomatics Contribution for the Valorisation Project in the Rocca of San Silvestro Landscape Site

    NASA Astrophysics Data System (ADS)

    Brocchini, D.; Chiabrando, F.; Colucci, E.; Sammartano, G.; Spanò, A.; Teppati Losè, L.; Villa, A.

    2017-05-01

    This paper proposes an emblematic project where several multi-sensor strategies for spatial data acquisition and management, range based and image based, were combined to create a series of integrated territorial and architectural scale products characterized by a rich multi-content nature. The work presented here was finalized in a test site that is composed by an ensemble of diversified cultural deposits; the objects that were surveyed and modelled range from the landscape with its widespread mining sites, the main tower with its defensive role, the urban configuration of the settlement, the building systems and techniques, a medieval mine. For this reason, the Rocca of San Silvestro represented a perfect test case, due to its complex and multi-stratified character. This archaeological site is a medieval fortified village near the municipality of Campiglia Marittima (LI), Italy. The Rocca is part of an Archaeological Mines Park and is included in the Parchi della Val di Cornia (a system of archaeological parks, natural parks and museums in the south-west of Tuscany). The fundamental role of a deep knowledge about a cultural artefact before the planning of a restoration and valorisation project is globally recognized; the qualitative and quantitative knowledge provided by geomatics techniques is part of this process. The paper will present the different techniques that were used, the products that were obtained and will focus on some mapping and WEB GIS applications and analyses that were performed and considerations that were made.

  10. Modelling multi-protein complexes using PELDOR distance measurements for rigid body minimisation experiments using XPLOR-NIH

    PubMed Central

    Hammond, Colin M.; Owen-Hughes, Tom; Norman, David G.

    2014-01-01

    Crystallographic and NMR approaches have provided a wealth of structural information about protein domains. However, often these domains are found as components of larger multi domain polypeptides or complexes. Orienting domains within such contexts can provide powerful new insight into their function. The combination of site specific spin labelling and Pulsed Electron Double Resonance (PELDOR) provide a means of obtaining structural measurements that can be used to generate models describing how such domains are oriented. Here we describe a pipeline for modelling the location of thio-reactive nitroxyl spin locations to engineered sties on the histone chaperone Vps75. We then use a combination of experimentally determined measurements and symmetry constraints to model the orientation in which homodimers of Vps75 associate to form homotetramers using the XPLOR-NIH platform. This provides a working example of how PELDOR measurements can be used to generate a structural model. PMID:25448300

  11. Work-related determinants of multi-site musculoskeletal pain among employees in the health care sector.

    PubMed

    Neupane, Subas; Nygård, Clas-Håkan; Oakman, Jodi

    2016-06-16

    Work-related musculoskeletal pain is a major occupational problem. Those with pain in multiple sites usually report worse health outcomes than those with pain in one site. This study explored prevalence and associated predictors of multi-site pain in health care sector employees. Survey responses from 1348 health care sector employees across three organisations (37% response rate) collected data on job satisfaction, work life balance, psychosocial and physical hazards, general health and work ability. Musculoskeletal discomfort was measured across 5 body regions with pain in ≥ 2 sites defined as multi-site pain. Generalized linear models were used to identify relationships between work-related factors and multi-site pain. Over 52% of the employees reported pain in multiple body sites and 19% reported pain in one site. Poor work life balance (PRR = 2.33, 95% CI = 1.06-5.14). physical (PRR = 7.58, 95% CI = 4.89-11.77) and psychosocial (PRR = 1.59, 95% CI = 1.00-2.57) hazard variables were related to multi-site pain (after controlling for age, gender, health and work ability. Older employees and females were more likely to report multi-site pain. Effective risk management of work related multi-site pain must include identification and control of psychosocial and physical hazards.

  12. A COMPARISON OF AIRFLOW PATTERNS FROM THE QUIC MODEL AND AN ATMOSPHERIC WIND TUNNEL FOR A TWO-DIMENSIONAL BUILDING ARRAY AND A MULTI-CITY BLOCK REGION NEAR THE WORLD TRADE CENTER SITE

    EPA Science Inventory

    Dispersion of pollutants in densely populated urban areas is a research area of clear importance. Currently, few numerical tools exist capable of describing airflow and dispersion patterns in these complex regions in a time efficient manner. (QUIC), Quick Urban & Industrial C...

  13. Tsunami vertical-evacuation planning in the U.S. Pacific Northwest as a geospatial, multi-criteria decision problem

    USGS Publications Warehouse

    Wood, Nathan; Jones, Jeanne; Schelling, John; Schmidtlein, Mathew

    2014-01-01

    Tsunami vertical-evacuation (TVE) refuges can be effective risk-reduction options for coastal communities with local tsunami threats but no accessible high ground for evacuations. Deciding where to locate TVE refuges is a complex risk-management question, given the potential for conflicting stakeholder priorities and multiple, suitable sites. We use the coastal community of Ocean Shores (Washington, USA) and the local tsunami threat posed by Cascadia subduction zone earthquakes as a case study to explore the use of geospatial, multi-criteria decision analysis for framing the locational problem of TVE siting. We demonstrate a mixed-methods approach that uses potential TVE sites identified at community workshops, geospatial analysis to model changes in pedestrian evacuation times for TVE options, and statistical analysis to develop metrics for comparing population tradeoffs and to examine influences in decision making. Results demonstrate that no one TVE site can save all at-risk individuals in the community and each site provides varying benefits to residents, employees, customers at local stores, tourists at public venues, children at schools, and other vulnerable populations. The benefit of some proposed sites varies depending on whether or not nearby bridges will be functioning after the preceding earthquake. Relative rankings of the TVE sites are fairly stable under various criteria-weighting scenarios but do vary considerably when comparing strategies to exclusively protect tourists or residents. The proposed geospatial framework can serve as an analytical foundation for future TVE siting discussions.

  14. Interleukin-8 responses of multi-layer gingival epithelia to subgingival biofilms: role of the "red complex" species.

    PubMed

    Belibasakis, Georgios N; Thurnheer, Thomas; Bostanci, Nagihan

    2013-01-01

    Periodontitis is an infectious inflammatory disease that results in the destruction of the tooth-supporting (periodontal) tissues. The Gram-negative anaerobic species Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola, (also known as the "red complex" species) are highly associated with subgingival biofilms at periodontitis-affected sites. A major chemokine produced by the gingival epithelium in response to biofilm challenge, is interleukin (IL)-8. The aim of this in vitro study was to investigate the relative effect of the "red complex" species as constituents of subgingival biofilms, on the regulation of IL-8 by gingival epithelia. Multi-layered organotypic human gingival epithelial cultures were challenged with a 10-species in vitro subgingival biofilm model, or its 7-species variant, excluding the "red complex". IL-8 gene expression and secretion analyses were performed by qPCR and ELISA, respectively. After 3 h, both biofilms up-regulated IL-8 gene expression, but the presence of the "red complex" resulted in 3-fold greater response. IL-8 secretion was also up-regulated by both biofilms, with no differences between them. After 24 h, the 10-species biofilm reduced IL-8 secretion to 50% of the control, but this was not affected when the "red complex" was absent. In conclusion, as part of biofilms, "red complex" species differentially regulate IL-8 in gingival epithelia, potentially affecting the chemotactic responses of the tissue.

  15. Excited state electron and energy relays in supramolecular dinuclear complexes revealed by ultrafast optical and X-ray transient absorption spectroscopy

    DOE PAGES

    Hayes, Dugan; Kohler, Lars; Hadt, Ryan G.; ...

    2017-11-28

    Here, the kinetics of photoinduced electron and energy transfer in a family of tetrapyridophenazine-bridged heteroleptic homo- and heterodinuclear copper(I) bis(phenanthroline)/ruthenium(II) polypyridyl complexes were studied using ultrafast optical and multi-edge X-ray transient absorption spectroscopies. This work combines the synthesis of heterodinuclear Cu(I)–Ru(II) analogs of the homodinuclear Cu(I)–Cu(I) targets with spectroscopic analysis and electronic structure calculations to first disentangle the dynamics at individual metal sites by taking advantage of the element and site specificity of X-ray absorption and theoretical methods. The excited state dynamical models developed for the heterodinuclear complexes are then applied to model the more challenging homodinuclear complexes. These resultsmore » suggest that both intermetallic charge and energy transfer can be observed in an asymmetric dinuclear copper complex in which the ground state redox potentials of the copper sites are offset by only 310 meV. We also demonstrate the ability of several of these complexes to effectively and unidirectionally shuttle energy between different metal centers, a property that could be of great use in the design of broadly absorbing and multifunctional multimetallic photocatalysts. This work provides an important step toward developing both a fundamental conceptual picture and a practical experimental handle with which synthetic chemists, spectroscopists, and theoreticians may collaborate to engineer cheap and efficient photocatalytic materials capable of performing coulombically demanding chemical transformations.« less

  16. Excited state electron and energy relays in supramolecular dinuclear complexes revealed by ultrafast optical and X-ray transient absorption spectroscopy

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

    Hayes, Dugan; Kohler, Lars; Hadt, Ryan G.

    Here, the kinetics of photoinduced electron and energy transfer in a family of tetrapyridophenazine-bridged heteroleptic homo- and heterodinuclear copper(I) bis(phenanthroline)/ruthenium(II) polypyridyl complexes were studied using ultrafast optical and multi-edge X-ray transient absorption spectroscopies. This work combines the synthesis of heterodinuclear Cu(I)–Ru(II) analogs of the homodinuclear Cu(I)–Cu(I) targets with spectroscopic analysis and electronic structure calculations to first disentangle the dynamics at individual metal sites by taking advantage of the element and site specificity of X-ray absorption and theoretical methods. The excited state dynamical models developed for the heterodinuclear complexes are then applied to model the more challenging homodinuclear complexes. These resultsmore » suggest that both intermetallic charge and energy transfer can be observed in an asymmetric dinuclear copper complex in which the ground state redox potentials of the copper sites are offset by only 310 meV. We also demonstrate the ability of several of these complexes to effectively and unidirectionally shuttle energy between different metal centers, a property that could be of great use in the design of broadly absorbing and multifunctional multimetallic photocatalysts. This work provides an important step toward developing both a fundamental conceptual picture and a practical experimental handle with which synthetic chemists, spectroscopists, and theoreticians may collaborate to engineer cheap and efficient photocatalytic materials capable of performing coulombically demanding chemical transformations.« less

  17. Early evidence for complex social structure in Proboscidea from a late Miocene trackway site in the United Arab Emirates

    PubMed Central

    Bibi, Faysal; Kraatz, Brian; Craig, Nathan; Beech, Mark; Schuster, Mathieu; Hill, Andrew

    2012-01-01

    Many living vertebrates exhibit complex social structures, evidence for the antiquity of which is limited to rare and exceptional fossil finds. Living elephants possess a characteristic social structure that is sex-segregated and multi-tiered, centred around a matriarchal family and solitary or loosely associated groups of adult males. Although the fossil record of Proboscidea is extensive, the origin and evolution of social structure in this clade is virtually unknown. Here, we present imagery and analyses of an extensive late Miocene fossil trackway site from the United Arab Emirates. The site of Mleisa 1 preserves exceptionally long trackways of a herd of at least 13 individuals of varying size transected by that of a single large individual, indicating the presence of both herding and solitary social modes. Trackway stride lengths and resulting body mass estimates indicate that the solitary individual was also the largest and therefore most likely a male. Sexual determination for the herd is equivocal, but the body size profile and number of individuals are commensurate with those of a modern elephant family unit. The Mleisa 1 trackways provide direct evidence for the antiquity of characteristic and complex social structure in Proboscidea. PMID:22357934

  18. Multi-site pain and working conditions as predictors of work ability in a 4-year follow-up among food industry employees.

    PubMed

    Neupane, S; Virtanen, P; Leino-Arjas, P; Miranda, H; Siukola, A; Nygård, C-H

    2013-03-01

    We investigated the separate and joint effects of multi-site musculoskeletal pain and physical and psychosocial exposures at work on future work ability. A survey was conducted among employees of a Finnish food industry company in 2005 (n = 1201) and a follow-up survey in 2009 (n = 734). Information on self-assessed work ability (current work ability on a scale from 0 to 10; 7 = poor work ability), multi-site musculoskeletal pain (pain in at least two anatomical areas of four), leisure-time physical activity, body mass index and physical and psychosocial exposures was obtained by questionnaire. The separate and joint effects of multi-site pain and work exposures on work ability at follow-up, among subjects with good work ability at baseline, were assessed by logistic regression, and p-values for the interaction derived. Compared with subjects with neither multi-site pain nor adverse work exposure, multi-site pain at baseline increased the risk of poor work ability at follow-up, allowing for age, gender, occupational class, body mass index and leisure-time physical activity. The separate effects of the work exposures on work ability were somewhat smaller than those of multi-site pain. Multi-site pain had an interactive effect with work environment and awkward postures, such that no association of multi-site pain with poor work ability was seen when work environment was poor or awkward postures present. The decline in work ability connected with multi-site pain was not increased by exposure to adverse physical or psychosocial factors at work. © 2012 European Federation of International Association for the Study of Pain Chapters.

  19. A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

    PubMed

    Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

    2017-01-10

    The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C Cdc20 ) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

  20. Selection of adequate site location during early stages of construction project management: A multi-criteria decision analysis approach

    NASA Astrophysics Data System (ADS)

    Marović, Ivan; Hanak, Tomaš

    2017-10-01

    In the management of construction projects special attention should be given to the planning as the most important phase of decision-making process. Quality decision-making based on adequate and comprehensive collaboration of all involved stakeholders is crucial in project’s early stages. Fundamental reasons for existence of this problem arise from: specific conditions of construction industry (final products are inseparable from the location i.e. location has a strong influence of building design and its structural characteristics as well as technology which will be used during construction), investors’ desires and attitudes, and influence of socioeconomic and environment aspects. Considering all mentioned reasons one can conclude that selection of adequate construction site location for future investment is complex, low structured and multi-criteria problem. To take into account all the dimensions, the proposed model for selection of adequate site location is devised. The model is based on AHP (for designing the decision-making hierarchy) and PROMETHEE (for pairwise comparison of investment locations) methods. As a result of mixing basis feature of both methods, operational synergies can be achieved in multi-criteria decision analysis. Such gives the decision-maker a sense of assurance, knowing that if the procedure proposed by the presented model has been followed, it will lead to a rational decision, carefully and systematically thought out.

  1. Outlook for grid service technologies within the @neurIST eHealth environment.

    PubMed

    Arbona, A; Benkner, S; Fingberg, J; Frangi, A F; Hofmann, M; Hose, D R; Lonsdale, G; Ruefenacht, D; Viceconti, M

    2006-01-01

    The aim of the @neurIST project is to create an IT infrastructure for the management of all processes linked to research, diagnosis and treatment development for complex and multi-factorial diseases. The IT infrastructure will be developed for one such disease, cerebral aneurysm and subarachnoid haemorrhage, but its core technologies will be transferable to meet the needs of other medical areas. Since the IT infrastructure for @neurIST will need to encompass data repositories, computational analysis services and information systems handling multi-scale, multi-modal information at distributed sites, the natural basis for the IT infrastructure is a Grid Service middleware. The project will adopt a service-oriented architecture because it aims to provide a system addressing the needs of medical researchers, clinicians and health care specialists (and their IT providers/systems) and medical supplier/consulting industries.

  2. Mapping wetlands in Nova Scotia with multi-beam RADARSAT-2 Polarimetric SAR, optical satellite imagery, and Lidar data

    NASA Astrophysics Data System (ADS)

    Jahncke, Raymond; Leblon, Brigitte; Bush, Peter; LaRocque, Armand

    2018-06-01

    Wetland maps currently in use by the Province of Nova Scotia, namely the Department of Natural Resources (DNR) wetland inventory map and the swamp wetland classes of the DNR forest map, need to be updated. In this study, wetlands were mapped in an area southwest of Halifax, Nova Scotia by classifying a combination of multi-date and multi-beam RADARSAT-2 C-band polarimetric SAR (polSAR) images with spring Lidar, and fall QuickBird optical data using the Random Forests (RF) classifier. The resulting map has five wetland classes (open-water/marsh complex, open bog, open fen, shrub/treed fen/bog, swamp), plus lakes and various upland classes. Its accuracy was assessed using data from 156 GPS wetland sites collected in 2012 and compared to the one obtained with the current wetland map of Nova Scotia. The best overall classification was obtained using a combination of Lidar, RADARSAT-2 HH, HV, VH, VV intensity with polarimetric variables, and QuickBird multispectral (89.2%). The classified image was compared to GPS validation sites to assess the mapping accuracy of the wetlands. It was first done considering a group consisting of all wetland classes including lakes. This showed that only 69.9% of the wetland sites were correctly identified when only the QuickBird classified image was used in the classification. With the addition of variables derived from lidar, the number of correctly identified wetlands increased to 88.5%. The accuracy remained the same with the addition of RADARSAT-2 (88.5%). When we tested the accuracy for identifying wetland classes (e.g. marsh complex vs. open bog) instead of grouped wetlands, the resulting wetland map performed best with either QuickBird and Lidar, or QuickBird, Lidar, and RADARSAT-2 (66%). The Province of Nova Scotia's current wetland inventory and its associated wetland classes (aerial-photo interpreted) were also assessed against the GPS wetland sites. This provincial inventory correctly identified 62.2% of the grouped wetlands and only 18.6% of the wetland classes. The current inventory's poor performance demonstrates the value of incorporating a combination of new data sources into the provincial wetland mapping.

  3. CHERISH (collaboration for hospitalised elders reducing the impact of stays in hospital): protocol for a multi-site improvement program to reduce geriatric syndromes in older inpatients.

    PubMed

    Mudge, Alison M; Banks, Merrilyn D; Barnett, Adrian G; Blackberry, Irene; Graves, Nicholas; Green, Theresa; Harvey, Gillian; Hubbard, Ruth E; Inouye, Sharon K; Kurrle, Sue; Lim, Kwang; McRae, Prue; Peel, Nancye M; Suna, Jessica; Young, Adrienne M

    2017-01-09

    Older inpatients are at risk of hospital-associated geriatric syndromes including delirium, functional decline, incontinence, falls and pressure injuries. These contribute to longer hospital stays, loss of independence, and death. Effective interventions to reduce geriatric syndromes remain poorly implemented due to their complexity, and require an organised approach to change care practices and systems. Eat Walk Engage is a complex multi-component intervention with structured implementation, which has shown reduced geriatric syndromes and length of stay in pilot studies at one hospital. This study will test effectiveness of implementing Eat Walk Engage using a multi-site cluster randomised trial to inform transferability of this intervention. A hybrid study design will evaluate the effectiveness and implementation strategy of Eat Walk Engage in a real-world setting. A multisite cluster randomised study will be conducted in 8 medical and surgical wards in 4 hospitals, with one ward in each site randomised to implement Eat Walk Engage (intervention) and one to continue usual care (control). Intervention wards will be supported to develop and implement locally tailored strategies to enhance early mobility, nutrition, and meaningful activities. Resources will include a trained, mentored facilitator, audit support, a trained healthcare assistant, and support by an expert facilitator team using the i-PARIHS implementation framework. Patient outcomes and process measures before and after intervention will be compared between intervention and control wards. Primary outcomes are any hospital-associated geriatric syndrome (delirium, functional decline, falls, pressure injuries, new incontinence) and length of stay. Secondary outcomes include discharge destination; 30-day mortality, function and quality of life; 6 month readmissions; and cost-effectiveness. Process measures including patient interviews, activity mapping and mealtime audits will inform interventions in each site and measure improvement progress. Factors influencing the trajectory of implementation success will be monitored on implementation wards. Using a hybrid design and guided by an explicit implementation framework, the CHERISH study will establish the effectiveness, cost-effectiveness and transferability of a successful pilot program for improving care of older inpatients, and identify features that support successful implementation. ACTRN12615000879561 registered prospectively 21/8/2015.

  4. Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag.

    PubMed

    Xue, Yongjie; Hou, Haobo; Zhu, Shujing

    2009-02-15

    Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01M NaNO(3). In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84mM in the single element system and 0.21mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH(50) (the pH at which 50% adsorption occurs) was found to follow the sequence Zn>Cu>Pb>Cd in single-element systems, but Pb>Cu>Zn>Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems.

  5. Multi-target screening mines hesperidin as a multi-potent inhibitor: Implication in Alzheimer's disease therapeutics.

    PubMed

    Chakraborty, Sandipan; Bandyopadhyay, Jaya; Chakraborty, Sourav; Basu, Soumalee

    2016-10-04

    Alzheimer's disease (AD) is the most frequent form of neurodegenerative disorder in elderly people. Involvement of several pathogenic events and their interconnections make this disease a complex disorder. Therefore, designing compounds that can inhibit multiple toxic pathways is the most attractive therapeutic strategy in complex disorders like AD. Here, we have designed a multi-tier screening protocol combining ensemble docking to mine BACE1 inhibitor, as well as 2-D QSAR models for anti-amyloidogenic and antioxidant activities. An in house developed phytochemical library of 200 phytochemicals has been screened through this multi-target procedure which mine hesperidin, a flavanone glycoside commonly found in citrus food items, as a multi-potent phytochemical in AD therapeutics. Steady-state and time-resolved fluorescence spectroscopy reveal that binding of hesperidin to the active site of BACE1 induces a conformational transition of the protein from open to closed form. Hesperidin docks close to the catalytic aspartate residues and orients itself in a way that blocks the cavity opening thereby precluding substrate binding. Hesperidin is a high affinity BACE1 inhibitor and only 500 nM of the compound shows complete inhibition of the enzyme activity. Furthermore, ANS and Thioflavin-T binding assay show that hesperidin completely inhibits the amyloid fibril formation which is further supported by atomic force microscopy. Hesperidin exhibits moderate ABTS(+) radical scavenging assay but strong hydroxyl radical scavenging ability, as evident from DNA nicking assay. Present study demonstrates the applicability of a novel multi-target screening procedure to mine multi-potent agents from natural origin for AD therapeutics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Integrative systems and synthetic biology of cell-matrix adhesion sites.

    PubMed

    Zamir, Eli

    2016-09-02

    The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

  7. Use of multi-opening burrow systems by black-footed ferrets

    USGS Publications Warehouse

    Biggins, Dean E.

    2012-01-01

    Multi-opening burrow systems constructed by prairie dogs (Cynomys) ostensibly provide escape routes when prairie dogs are pursued by predators capable of entering the burrows, such as black-footed ferrets (Mustela nigripes), or by predators that can rapidly dig into the tunnels, such as American badgers (Taxidea taxus). Because badgers also prey on ferrets, ferrets might similarly benefit from multi-opening burrow systems. Using an air blower, white-tailed prairie dog (Cynomys leucurus) burrow openings were tested for connectivity on plots occupied by black-footed ferrets and on randomly selected plots in Wyoming. Significantly more connected openings were found on ferret-occupied plots than on random plots. Connected openings might be due to modifications by ferrets in response to plugging by prairie dogs, due to selection by ferrets for complex systems with multiple openings that are already unobstructed, or simply due to ferrets lingering at kill sites that were multi-opening systems selected by their prairie dog prey.

  8. Ab initio single and multideterminant methods used in the determination of reduction potentials and magnetic properties of Rieske ferredoxins

    NASA Astrophysics Data System (ADS)

    Powers, Nathan Lee

    2008-10-01

    The [Fe2S2]2+/[Fe2S 2]+ electronic structure of seven Rieske protein active sites (bovine mitochondrial cytochrome bc1 complex, spinach chloroplast cytochrome b6f complex, Rieske-type ferredoxin associated with biphenyl dioxygenase from Burkholderia cepacia, yeast cytochrome bcl complex from Saccharomyces cerevisiae, Rieske subunit of arsenite oxidase from Alcaligenes faecalis, respiratory-type Rieske protein from Thermus thermophilus, and Rieske protein II (soxF) from Sulfolobus acidocaldarius), which lie in a reduction potential range from -150 mV to 375 mV, have been studied by both single and multi-determinant quantum mechanical methods. Calculated reduction potentials and magnetic properties are found comparable to experimental values.

  9. Overview of software development at the parabolic dish test site

    NASA Technical Reports Server (NTRS)

    Miyazono, C. K.

    1985-01-01

    The development history of the data acquisition and data analysis software is discussed. The software development occurred between 1978 and 1984 in support of solar energy module testing at the Jet Propulsion Laboratory's Parabolic Dish Test Site, located within Edwards Test Station. The development went through incremental stages, starting with a simple single-user BASIC set of programs, and progressing to the relative complex multi-user FORTRAN system that was used until the termination of the project. Additional software in support of testing is discussed including software in support of a meteorological subsystem and the Test Bed Concentrator Control Console interface. Conclusions and recommendations for further development are discussed.

  10. Modeling and simulation of the data communication network at the ASRM Facility

    NASA Technical Reports Server (NTRS)

    Nirgudkar, R. P.; Moorhead, R. J.; Smith, W. D.

    1994-01-01

    This paper describes the modeling and simulation of the communication network for the NASA Advanced Solid Rocket Motor (ASRM) facility under construction at Yellow Creek near Luka, Mississippi. Manufacturing, testing, and operations at the ASRM site will be performed in different buildings scattered over an 1800 acre site. These buildings are interconnected through a local area network (LAN), which will contain one logical Fiber Distributed Data Interface (FDDI) ring acting as a backbone for the whole complex. The network contains approximately 700 multi-vendor workstations, 22 multi-vendor workcells, and 3 VAX clusters interconnected via Ethernet and FDDI. The different devices produce appreciably different traffic patterns, each pattern will be highly variable, and some patterns will be very bursty. Most traffic is between the VAX clusters and the other devices. Comdisco's Block Oriented Network Simulator (BONeS) has been used for network simulation. The two primary evaluation parameters used to judge the expected network performance are throughput and delay.

  11. Multi-spectroscopic and molecular modeling approaches to elucidate the binding interaction between bovine serum albumin and darunavir, a HIV protease inhibitor

    NASA Astrophysics Data System (ADS)

    Shi, Jie-Hua; Zhou, Kai-Li; Lou, Yan-Yue; Pan, Dong-Qi

    2018-01-01

    Darunavir (DRV), a second-generation HIV protease inhibitor, is widely used across the world as an important component of HIV therapy. The interaction of DRV with bovine serum albumin (BSA), a major carrier protein, has been studied under simulated physiological conditions (pH 7.4) by multi-spectroscopic techniques in combination with molecular modeling. Fluorescence data revealed that the intrinsic fluorescence of BSA was quenched by DRV in terms of a static quenching procedure due to the formation of the DRV-BSA complex. The results indicated the presence of single weak affinity binding site ( 103 M- 1, 310 K) on protein. The thermodynamic parameters, namely enthalpy change (ΔH0), entropy change (ΔS0) and Gibbs free energy change (ΔG0) were calculated, which signified that the binding reaction was spontaneous, the main binding forces were hydrogen bonding and van der Waals forces. Importantly, competitive binding experiments with three site probes, phenylbutazone (in sub-domain IIA, site I), ibuprofen (in sub-domain IIIA, site II) and artemether (in the interface between sub-domain IIA and IIB, site II'), suggested that DRV was preferentially bound to the hydrophobic cavity in site II' of BSA, and this finding was validated by the docking results. Additionally, synchronous fluorescence, three-dimensional fluorescence and Resonance Rayleigh Scattering (RRS) spectroscopy gave qualitative information on the conformational changes of BSA upon adding DRV, while quantitative data were obtained with Fourier transform infrared spectroscopy (FT-IR).

  12. Atmosphere to Electrons (A2e): Enabling the Wind Plant of Tomorrow

    ScienceCinema

    Zayas, Jose; Derby, Mike; Ralston, Kiersten; Clark, Charlton; Brake, Dan; Johnson, Nick

    2018-01-16

    Atmosphere to Electrons (A2e) is a multi-year U.S. Department of Energy (DOE) research initiative targeting significant reductions in the cost of wind energy through an improved understanding of the complex physics governing electricity generation by wind plants. The goal of A2e is to ensure future wind plants are sited, built, and operated in a way that produces the most cost-effective, usable electric power.

  13. Assessing the challenges of multi-scope clinical research sites: an example from NIH HIV/AIDS clinical trials networks.

    PubMed

    Rosas, Scott R; Cope, Marie T; Villa, Christie; Motevalli, Mahnaz; Utech, Jill; Schouten, Jeffrey T

    2014-04-01

    Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi-network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross-network coordinating centre, and creating common budget and payment mechanisms. The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings. © 2013 John Wiley & Sons Ltd.

  14. Chemical Screens Against A Reconstituted Multi-Protein Complex: Myricetin Blocks DnaJ Regulation of DnaK through an Allosteric Mechanism

    PubMed Central

    Chang, Lyra; Miyata, Yoshinari; Ung, Peter M. U.; Bertelsen, Eric B.; McQuade, Thomas J.; Carlson, Heather A.; Zuiderweg, Erik R. P.; Gestwicki, Jason E.

    2011-01-01

    SUMMARY DnaK is a molecular chaperone responsible for multiple aspects of proteostasis. The intrinsically slow ATPase activity of DnaK is stimulated by its co-chaperone, DnaJ, and these proteins often work in concert. To identify inhibitors, we screened plant-derived extracts against a re-constituted mixture of DnaK and DnaJ. This approach resulted in the identification of flavonoids, including myricetin, which inhibited activity by up to 75%. Interestingly, myricetin prevented DnaJ-mediated stimulation of ATPase activity, with minimal impact on either DnaK’s intrinsic turnover rate or its stimulation by another co-chaperone, GrpE. Using NMR, we found that myricetin binds DnaK at an unanticipated site between the IB and IIB subdomains and that it allosterically blocked binding of DnaJ. Together, these results highlight a “gray box” screening approach, which approximates a limited amount of the complexity expected in physiological, multi-protein systems. PMID:21338918

  15. Landfill site selection using combination of GIS and fuzzy AHP, a case study: Iranshahr, Iran.

    PubMed

    Torabi-Kaveh, M; Babazadeh, R; Mohammadi, S D; Zaresefat, M

    2016-03-09

    One of the most important recent challenges in solid waste management throughout the world is site selection of sanitary landfill. Commonly, because of simultaneous effects of social, environmental, and technical parameters on suitability of a landfill site, landfill site selection is a complex process and depends on several criteria and regulations. This study develops a multi-criteria decision analysis (MCDA) process, which combines geographic information system (GIS) analysis with a fuzzy analytical hierarchy process (FAHP), to determine suitable sites for landfill construction in Iranshahr County, Iran. The GIS was used to calculate and classify selected criteria and FAHP was used to assess the criteria weights based on their effectiveness on selection of potential landfill sites. Finally, a suitability map was prepared by overlay analyses and suitable areas were identified. Four suitability classes within the study area were separated, including high, medium, low, and very low suitability areas, which represented 18%, 15%, 55%, and 12% of the study area, respectively. © The Author(s) 2016.

  16. Site-Specific Three-Color Labeling of α-Synuclein via Conjugation to Uniquely Reactive Cysteines during Assembly by Native Chemical Ligation.

    PubMed

    Lee, Taehyung C; Moran, Crystal R; Cistrone, Philip A; Dawson, Philip E; Deniz, Ashok A

    2018-04-12

    Single-molecule fluorescence is widely used to study conformational complexity in proteins, and has proven especially valuable with intrinsically disordered proteins (IDPs). Protein studies using dual-color single-molecule Förster resonance energy transfer (smFRET) are now quite common, but many could benefit from simultaneous measurement of multiple distances through multi-color labeling. Such studies, however, have suffered from limitations in site-specific incorporation of more than two dyes per polypeptide. Here we present a fully site-specific three-color labeling scheme for α-synuclein, an IDP with important putative functions and links to Parkinson disease. The convergent synthesis combines native chemical ligation with regiospecific cysteine protection of expressed protein fragments to permit highly controlled labeling via standard cysteine-maleimide chemistry, enabling more global smFRET studies. Furthermore, this modular approach is generally compatible with recombinant proteins and expandable to accommodate even more complex experiments, such as by labeling with additional colors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Protonation of Different Goethite Surfaces - Unified Models for NaNO3 and NaCl Media.

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

    Lutzenkirchen, Johannes; Boily, Jean F.; Gunneriusson, Lars

    2008-01-01

    Acid-base titration data for two goethites samples in sodium nitrate and sodium chloride media are discussed. The data are modelled based on various surface complexation models in the framework of the MUlti SIte Complexation (MUSIC) model. Various assumptions with respect to the goethite morphology are considered in determining the site density of the surface functional groups. The results from the various model applications are not statistically significant in terms of goodness of fit. More importantly, various published assumptions with respect to the goethite morphology (i.e. the contributions of different crystal planes and their repercussions on the “overall” site densities ofmore » the various surface functional groups) do not significantly affect the final model parameters. The simultaneous fit of the chloride and nitrate data results in electrolyte binding constants, which are applicable over a wide range of electrolyte concentrations including mixtures of chloride and nitrate. Model parameters for the high surface area goethite sample are in excellent agreement with parameters that were independently obtained by another group on different goethite titration data sets.« less

  18. Structure-Guided Design of Peptides as Tools to Probe the Protein-Protein Interaction between Cullin-2 and Elongin BC Substrate Adaptor in Cullin RING E3 Ubiquitin Ligases.

    PubMed

    Cardote, Teresa A F; Ciulli, Alessio

    2017-09-21

    Cullin RING E3 ubiquitin ligases (CRLs) are large dynamic multi-subunit complexes that control the fate of many proteins in cells. CRLs are attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. Herein we describe a structure-guided biophysical approach to probe the protein-protein interaction (PPI) between the Cullin-2 scaffold protein and the adaptor subunits Elongin BC within the context of the von Hippel-Lindau complex (CRL2 VHL ) using peptides. Two peptides were shown to bind at the targeted binding site on Elongin C, named the "EloC site", with micromolar dissociation constants, providing a starting point for future optimization. Our results suggest ligandability of the EloC binding site to short linear peptides, unveiling the opportunity and challenges to develop small molecules that have the potential to target selectively the Cul2-adaptor PPI within CRLs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. A comparison of single- and multi-site calibration and validation: a case study of SWAT in the Miyun Reservoir watershed, China

    NASA Astrophysics Data System (ADS)

    Bai, Jianwen; Shen, Zhenyao; Yan, Tiezhu

    2017-09-01

    An essential task in evaluating global water resource and pollution problems is to obtain the optimum set of parameters in hydrological models through calibration and validation. For a large-scale watershed, single-site calibration and validation may ignore spatial heterogeneity and may not meet the needs of the entire watershed. The goal of this study is to apply a multi-site calibration and validation of the Soil andWater Assessment Tool (SWAT), using the observed flow data at three monitoring sites within the Baihe watershed of the Miyun Reservoir watershed, China. Our results indicate that the multi-site calibration parameter values are more reasonable than those obtained from single-site calibrations. These results are mainly due to significant differences in the topographic factors over the large-scale area, human activities and climate variability. The multi-site method involves the division of the large watershed into smaller watersheds, and applying the calibrated parameters of the multi-site calibration to the entire watershed. It was anticipated that this case study could provide experience of multi-site calibration in a large-scale basin, and provide a good foundation for the simulation of other pollutants in followup work in the Miyun Reservoir watershed and other similar large areas.

  20. The At Home/Chez Soi trial protocol: a pragmatic, multi-site, randomised controlled trial of a Housing First intervention for homeless individuals with mental illness in five Canadian cities

    PubMed Central

    Streiner, David L; Adair, Carol; Aubry, Tim; Barker, Jayne; Distasio, Jino; Hwang, Stephen W; Komaroff, Janina; Latimer, Eric; Somers, Julian; Zabkiewicz, Denise M

    2011-01-01

    Introduction Housing First is a complex housing and support intervention for homeless individuals with mental health problems. It has a sufficient knowledge base and interest to warrant a test of wide-scale implementation in various settings. This protocol describes the quantitative design of a Canadian five city, $110 million demonstration project and provides the rationale for key scientific decisions. Methods A pragmatic, mixed methods, multi-site field trial of the effectiveness of Housing First in Vancouver, Winnipeg, Toronto, Montreal and Moncton, is randomising approximately 2500 participants, stratified by high and moderate need levels, into intervention and treatment as usual groups. Quantitative outcome measures are being collected over a 2-year period and a qualitative process evaluation is being completed. Primary outcomes are housing stability, social functioning and, for the economic analyses, quality of life. Hierarchical linear modelling is the primary data analytic strategy. Ethics and dissemination Research ethics board approval has been obtained from 11 institutions and a safety and adverse events committee is in place. The results of the multi-site analyses of outcomes at 12 months and 2 years will be reported in a series of core scientific journal papers. Extensive knowledge exchange activities with non-academic audiences will occur throughout the duration of the project. Trial registration number This study has been registered with the International Standard Randomised Control Trial Number Register and assigned ISRCTN42520374. PMID:22102645

  1. A multi-scale spatial approach to address environmental effects of small hydropower development.

    PubMed

    McManamay, Ryan A; Samu, Nicole; Kao, Shih-Chieh; Bevelhimer, Mark S; Hetrick, Shelaine C

    2015-01-01

    Hydropower development continues to grow worldwide in developed and developing countries. While the ecological and physical responses to dam construction have been well documented, translating this information into planning for hydropower development is extremely difficult. Very few studies have conducted environmental assessments to guide site-specific or widespread hydropower development. Herein, we propose a spatial approach for estimating environmental effects of hydropower development at multiple scales, as opposed to individual site-by-site assessments (e.g., environmental impact assessment). Because the complex, process-driven effects of future hydropower development may be uncertain or, at best, limited by available information, we invested considerable effort in describing novel approaches to represent environmental concerns using spatial data and in developing the spatial footprint of hydropower infrastructure. We then use two case studies in the US, one at the scale of the conterminous US and another within two adjoining rivers basins, to examine how environmental concerns can be identified and related to areas of varying energy capacity. We use combinations of reserve-design planning and multi-metric ranking to visualize tradeoffs among environmental concerns and potential energy capacity. Spatial frameworks, like the one presented, are not meant to replace more in-depth environmental assessments, but to identify information gaps and measure the sustainability of multi-development scenarios as to inform policy decisions at the basin or national level. Most importantly, the approach should foster discussions among environmental scientists and stakeholders regarding solutions to optimize energy development and environmental sustainability.

  2. Factors predicting change in hospital safety climate and capability in a multi-site patient safety collaborative: a longitudinal survey study.

    PubMed

    Benn, Jonathan; Burnett, Susan; Parand, Anam; Pinto, Anna; Vincent, Charles

    2012-07-01

    The study had two specific objectives: (1) To analyse change in a survey measure of organisational patient safety climate and capability (SCC) resulting from participation in the UK Safer Patients Initiative and (2) To investigate the role of a range of programme and contextual factors in predicting change in SCC scores. Single group longitudinal design with repeated measurement at 12-month follow-up. Multiple service areas within NHS hospital sites across England, Wales, Scotland and Northern Ireland. Stratified sample of 284 respondents representing programme teams at 19 hospital sites. A complex intervention comprising a multi-component quality improvement collaborative focused upon patient safety and designed to impact upon hospital leadership, communication, organisation and safety climate. A survey including a 31-item SCC scale was administered at two time-points. Modest but significant positive movement in SCC score was observed between the study time-points. Individual programme responsibility, availability of early adopters, multi-professional collaboration and extent of process measurement were significant predictors of change in SCC. Hospital type and size, along with a range of programme preconditions, were not found to be significant. A range of social, cultural and organisational factors may be sensitive to this type of intervention but the measurable effect is small. Supporting critical local programme implementation factors may be an effective strategy in achieving development in organisational patient SCC, regardless of contextual factors and organisational preconditions.

  3. An Experimental and Theoretical Evaluation of Multi-site Cadmium(II) Exchange in Designed Three-Stranded Coiled Coil Peptides

    PubMed Central

    Chakraborty, Saumen; Iranzo, Olga; Zuiderweg, Erik R.P.; Pecoraro, Vincent L.

    2012-01-01

    An important factor that defines the toxicity of elements such as cadmium(II), mercury(II), and lead(II) with biological macromolecules is metal ion exchange dynamics. Intriguingly, little is known about the fundamental rates and mechanisms of metal ion exchange into proteins, especially helical bundles. Herein, we investigate the exchange kinetics of cadmium(II) using de novo designed three-stranded coiled coil peptides that contain metal complexing cysteine thiolates as a model for the incorporation of this ion into trimeric, parallel helical bundles. Peptides were designed containing both single cadmium(II) binding site, GrandL12AL16C [Grand=AcG-(LKALEEK)5-GNH2], GrandL26AL30C, and GrandL26AE28QL30C, as well as GrandL12AL16CL26AL30C with two cadmium(II) binding sites. The binding of cadmium(II) to any of these sites is of high affinity (KA > 3×107 M−1). Using 113Cd NMR spectroscopy, cadmium(II) binding to these designed peptides was monitored. While the cadmium(II) binding is in extreme slow exchange without showing any chemical shift changes, incremental line broadening for the bound 113cadmium(II) signal is observed when excess 113cadmium(II) is titrated into the peptides. Most dramatically, for one site, L26AL30C, all 113cadmium(II) NMR signals disappear once a 1.7:1 ratio of cadmium(II)/(peptide)3 is reached. The observed processes are not compatible with simple “free-bound” two-site exchange kinetics at any time regime. The experimental results can, however, be simulated in detail with a multi-site binding model, which features additional cadmium(II) binding site(s) which, once occupied, perturb the primary binding site. This model is expanded into differential equations for five-site NMR chemical exchange. The numerical integration of these equations exhibits progressive loss of the primary site NMR signal without a chemical shift change and with limited line broadening, in good agreement with the observed experimental data. The mathematical model is interpreted in molecular terms as representing binding of excess cadmium(II) to surface Glu residues located at the helical interfaces. In the absence of cadmium(II), the Glu residues stabilize the three-helical structure though salt bridge interactions with surface Lys residues. We hypothesize that cadmium(II) interferes with these surface ion pairs, destabilizing the helical structure, and perturbing the primary cadmium(II) binding site. This hypothesis is supported by the observation that the cadmium(II)-excess line broadening is attenuated in GrandL26AE28QL30C where a surface Glu(28), close to the metal binding site, was changed to Gln. The external binding site may function as an entry pathway for cadmium(II) to find its internal binding site following a molecular rearrangement which may serve as a basis for our understanding of metal complexation, transport and exchange in complex native systems containing α-helical bundles. PMID:22394049

  4. Probing binding hot spots at protein-RNA recognition sites.

    PubMed

    Barik, Amita; Nithin, Chandran; Karampudi, Naga Bhushana Rao; Mukherjee, Sunandan; Bahadur, Ranjit Prasad

    2016-01-29

    We use evolutionary conservation derived from structure alignment of polypeptide sequences along with structural and physicochemical attributes of protein-RNA interfaces to probe the binding hot spots at protein-RNA recognition sites. We find that the degree of conservation varies across the RNA binding proteins; some evolve rapidly compared to others. Additionally, irrespective of the structural class of the complexes, residues at the RNA binding sites are evolutionary better conserved than those at the solvent exposed surfaces. For recognitions involving duplex RNA, residues interacting with the major groove are better conserved than those interacting with the minor groove. We identify multi-interface residues participating simultaneously in protein-protein and protein-RNA interfaces in complexes where more than one polypeptide is involved in RNA recognition, and show that they are better conserved compared to any other RNA binding residues. We find that the residues at water preservation site are better conserved than those at hydrated or at dehydrated sites. Finally, we develop a Random Forests model using structural and physicochemical attributes for predicting binding hot spots. The model accurately predicts 80% of the instances of experimental ΔΔG values in a particular class, and provides a stepping-stone towards the engineering of protein-RNA recognition sites with desired affinity. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Multi-Sited Global Ethnography and Travel: Gendered Journeys in Three Registers

    ERIC Educational Resources Information Center

    Epstein, Debbie; Fahey, Johannah; Kenway, Jane

    2013-01-01

    This paper joins a barely begun conversation about multi-sited and global ethnography in educational research; a conversation that is likely to intensify along with growing interest in the links between education, globalisation, internationalisation and transnationalism. Drawing on an ongoing multi-sited global ethnography of elite schools and…

  6. Predicting lymphatic filariasis transmission and elimination dynamics using a multi-model ensemble framework.

    PubMed

    Smith, Morgan E; Singh, Brajendra K; Irvine, Michael A; Stolk, Wilma A; Subramanian, Swaminathan; Hollingsworth, T Déirdre; Michael, Edwin

    2017-03-01

    Mathematical models of parasite transmission provide powerful tools for assessing the impacts of interventions. Owing to complexity and uncertainty, no single model may capture all features of transmission and elimination dynamics. Multi-model ensemble modelling offers a framework to help overcome biases of single models. We report on the development of a first multi-model ensemble of three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and evaluate its predictive performance in comparison with that of the constituents using calibration and validation data from three case study sites, one each from the three major LF endemic regions: Africa, Southeast Asia and Papua New Guinea (PNG). We assessed the performance of the respective models for predicting the outcomes of annual MDA strategies for various baseline scenarios thought to exemplify the current endemic conditions in the three regions. The results show that the constructed multi-model ensemble outperformed the single models when evaluated across all sites. Single models that best fitted calibration data tended to do less well in simulating the out-of-sample, or validation, intervention data. Scenario modelling results demonstrate that the multi-model ensemble is able to compensate for variance between single models in order to produce more plausible predictions of intervention impacts. Our results highlight the value of an ensemble approach to modelling parasite control dynamics. However, its optimal use will require further methodological improvements as well as consideration of the organizational mechanisms required to ensure that modelling results and data are shared effectively between all stakeholders. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Comprehensive insight into the binding of sunitinib, a multi-targeted anticancer drug to human serum albumin

    NASA Astrophysics Data System (ADS)

    Kabir, Md. Zahirul; Tee, Wei-Ven; Mohamad, Saharuddin B.; Alias, Zazali; Tayyab, Saad

    2017-06-01

    Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04 × 104 M-1), obtained at 298 K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.

  8. A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

    PubMed Central

    Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

    2017-01-01

    The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment. DOI: http://dx.doi.org/10.7554/eLife.22513.001 PMID:28072388

  9. KSC-2014-3527

    NASA Image and Video Library

    2014-08-14

    CAPE CANAVERAL, Fla. – A storm is brewing over Launch Complex 39 at NASA’s Kennedy Space Center in Florida. At left are the news networks' facilities on the NASA Press Site. At right is the behemoth Vehicle Assembly Building. Kennedy's Ground Support Development and Operations Program is hard at work transforming the center's facilities into a multi-user spaceport, when the weather permits. For more on Kennedy Space Center, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Ben Smegelsky

  10. Multi-isotope (carbon and chlorine) analysis for fingerprinting and site characterization at a fractured bedrock aquifer contaminated by chlorinated ethenes.

    PubMed

    Palau, Jordi; Marchesi, Massimo; Chambon, Julie C C; Aravena, Ramon; Canals, Àngels; Binning, Philip J; Bjerg, Poul L; Otero, Neus; Soler, Albert

    2014-03-15

    The use of compound specific multi-isotope approach (C and Cl) in the characterization of a chlorinated ethenes contaminated fractured aquifer allows the identification of several sources and contaminant plumes, as well as the occurrence of biodegradation and mixing processes. The study site is located in Spain with contamination resulting in groundwater concentrations of up to 50mg/L of trichloroethene (TCE), the most abundant chlorinated ethene, and 7 mg/L of tetrachloroethene (PCE). The potential sources of contamination including abandoned barrels, an underground tank, and a disposal lagoon, showed a wide range in δ(13)C values from -15.6 to -40.5‰ for TCE and from -18.5 to -32.4‰ for PCE, allowing the use of isotope fingerprinting for tracing of the origin and migration of these contaminants in the aquifer. In contrast, there is no difference between the δ(37)Cl values for TCE in the contaminant sources, ranging from +0.53 to +0.66‰. Variations of δ(37)Cl and δ(13)C in the different contaminant plumes were used to investigate the role of biodegradation in groundwater. Moreover, the isotopic data were incorporated into a reactive transport model for determination of whether the isotope pattern observed downstream from the tank's source could be explained by the simultaneous effect of mixing and biodegradation. The results demonstrate that a multi-isotope approach is a valuable tool for characterization of complex sites such as fractured bedrock aquifer contaminated by multiple sources, providing important information which can be used by consultants and site managers to prioritize and design more successful remediation strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. A simplified gross primary production and evapotranspiration model for boreal coniferous forests - is a generic calibration sufficient?

    NASA Astrophysics Data System (ADS)

    Minunno, F.; Peltoniemi, M.; Launiainen, S.; Aurela, M.; Lindroth, A.; Lohila, A.; Mammarella, I.; Minkkinen, K.; Mäkelä, A.

    2015-07-01

    The problem of model complexity has been lively debated in environmental sciences as well as in the forest modelling community. Simple models are less input demanding and their calibration involves a lower number of parameters, but they might be suitable only at local scale. In this work we calibrated a simplified ecosystem process model (PRELES) to data from multiple sites and we tested if PRELES can be used at regional scale to estimate the carbon and water fluxes of Boreal conifer forests. We compared a multi-site (M-S) with site-specific (S-S) calibrations. Model calibrations and evaluations were carried out by the means of the Bayesian method; Bayesian calibration (BC) and Bayesian model comparison (BMC) were used to quantify the uncertainty in model parameters and model structure. To evaluate model performances BMC results were combined with more classical analysis of model-data mismatch (M-DM). Evapotranspiration (ET) and gross primary production (GPP) measurements collected in 10 sites of Finland and Sweden were used in the study. Calibration results showed that similar estimates were obtained for the parameters at which model outputs are most sensitive. No significant differences were encountered in the predictions of the multi-site and site-specific versions of PRELES with exception of a site with agricultural history (Alkkia). Although PRELES predicted GPP better than evapotranspiration, we concluded that the model can be reliably used at regional scale to simulate carbon and water fluxes of Boreal forests. Our analyses underlined also the importance of using long and carefully collected flux datasets in model calibration. In fact, even a single site can provide model calibrations that can be applied at a wider spatial scale, since it covers a wide range of variability in climatic conditions.

  12. Multi-site precipitation downscaling using a stochastic weather generator

    NASA Astrophysics Data System (ADS)

    Chen, Jie; Chen, Hua; Guo, Shenglian

    2018-03-01

    Statistical downscaling is an efficient way to solve the spatiotemporal mismatch between climate model outputs and the data requirements of hydrological models. However, the most commonly-used downscaling method only produces climate change scenarios for a specific site or watershed average, which is unable to drive distributed hydrological models to study the spatial variability of climate change impacts. By coupling a single-site downscaling method and a multi-site weather generator, this study proposes a multi-site downscaling approach for hydrological climate change impact studies. Multi-site downscaling is done in two stages. The first stage involves spatially downscaling climate model-simulated monthly precipitation from grid scale to a specific site using a quantile mapping method, and the second stage involves the temporal disaggregating of monthly precipitation to daily values by adjusting the parameters of a multi-site weather generator. The inter-station correlation is specifically considered using a distribution-free approach along with an iterative algorithm. The performance of the downscaling approach is illustrated using a 10-station watershed as an example. The precipitation time series derived from the National Centers for Environment Prediction (NCEP) reanalysis dataset is used as the climate model simulation. The precipitation time series of each station is divided into 30 odd years for calibration and 29 even years for validation. Several metrics, including the frequencies of wet and dry spells and statistics of the daily, monthly and annual precipitation are used as criteria to evaluate the multi-site downscaling approach. The results show that the frequencies of wet and dry spells are well reproduced for all stations. In addition, the multi-site downscaling approach performs well with respect to reproducing precipitation statistics, especially at monthly and annual timescales. The remaining biases mainly result from the non-stationarity of NCEP precipitation. Overall, the proposed approach is efficient for generating multi-site climate change scenarios that can be used to investigate the spatial variability of climate change impacts on hydrology.

  13. Shared worlds: multi-sited ethnography and nursing research.

    PubMed

    Molloy, Luke; Walker, Kim; Lakeman, Richard

    2017-03-22

    Background Ethnography, originally developed for the study of supposedly small-scale societies, is now faced with an increasingly mobile, changing and globalised world. Cultural identities can exist without reference to a specific location and extend beyond regional and national boundaries. It is therefore no longer imperative that the sole object of the ethnographer's practice should be a geographically bounded site. Aim To present a critical methodological review of multi-sited ethnography. Discussion Understanding that it can no longer be taken with any certainty that location alone determines culture, multi-sited ethnography provides a method of contextualising multi-sited social phenomena. The method enables researchers to examine social phenomena that are simultaneously produced in different locations. It has been used to undertake cultural analysis of diverse areas such as organ trafficking, global organisations, technologies and anorexia. Conclusion The authors contend that multi-sited ethnography is particularly suited to nursing research as it provides researchers with an ethnographic method that is more relevant to the interconnected world of health and healthcare services. Implications for practice Multi-sited ethnography provides nurse researchers with an approach to cultural analysis in areas such as the social determinants of health, healthcare services and the effects of health policies across multiple locations.

  14. Relations between rainfall–runoff-induced erosion and aeolian deposition at archaeological sites in a semi-arid dam-controlled river corridor

    USGS Publications Warehouse

    Collins, Brian D.; Bedford, David; Corbett, Skye C.; Fairley, Helen C.; Cronkite-Ratcliff, Collin

    2016-01-01

    Process dynamics in fluvial-based dryland environments are highly complex with fluvial, aeolian, and alluvial processes all contributing to landscape change. When anthropogenic activities such as dam-building affect fluvial processes, the complexity in local response can be further increased by flood- and sediment-limiting flows. Understanding these complexities is key to predicting landscape behavior in drylands and has important scientific and management implications, including for studies related to paleoclimatology, landscape ecology evolution, and archaeological site context and preservation. Here we use multi-temporal LiDAR surveys, local weather data, and geomorphological observations to identify trends in site change throughout the 446-km-long semi-arid Colorado River corridor in Grand Canyon, Arizona, USA, where archaeological site degradation related to the effects of upstream dam operation is a concern. Using several site case studies, we show the range of landscape responses that might be expected from concomitant occurrence of dam-controlled fluvial sand bar deposition, aeolian sand transport, and rainfall-induced erosion. Empirical rainfall-erosion threshold analyses coupled with a numerical rainfall–runoff–soil erosion model indicate that infiltration-excess overland flow and gullying govern large-scale (centimeter- to decimeter-scale) landscape changes, but that aeolian deposition can in some cases mitigate gully erosion. Whereas threshold analyses identify the normalized rainfall intensity (defined as the ratio of rainfall intensity to hydraulic conductivity) as the primary factor governing hydrologic-driven erosion, assessment of false positives and false negatives in the dataset highlight topographic slope as the next most important parameter governing site response. Analysis of 4+ years of high resolution (four-minute) weather data and 75+ years of low resolution (daily) climate records indicates that dryland erosion is dependent on short-term, storm-driven rainfall intensity rather than cumulative rainfall, and that erosion can occur outside of wet seasons and even wet years. These results can apply to other similar semi-arid landscapes where process complexity may not be fully understood.

  15. Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA.

    PubMed

    Hartzell, Sharon E; Unger, Michael A; McGee, Beth L; Wilson, Sacoby M; Yonkos, Lance T

    2017-10-01

    Estuarine sediments in regions with prolonged histories of industrial activity are often laden to significant depths with complex contaminant mixtures, including trace metals and persistent organic pollutants. Given the complexity of assessing risks from multi-contaminant exposures, the direct measurement of impacts to biological receptors is central to characterizing contaminated sediment sites. Though biological consequences are less commonly assessed at depth, laboratory-based toxicity testing of subsurface sediments can be used to delineate the scope of contamination at impacted sites. The extent and depth of sediment toxicity in Bear Creek, near Baltimore, Maryland, USA, was delineated using 10-day acute toxicity tests with the estuarine amphipod Leptocheirus plumulosus, and chemical analysis of trace metals and persistent organic pollutants. A gradient of toxicity was demonstrated in surface sediments with 21 of 22 tested sites differing significantly from controls. Effects were most pronounced (100% lethality) at sites proximate to a historic industrial complex. Sediments from eight of nine core samples to depths of 80 cm were particularly impacted (i.e., caused significant lethality to L. plumulosus) even in locations overlain with relatively non-toxic surface sediments, supporting a conclusion that toxicity observed at the surface (top 2 cm) does not adequately predict toxicity at depth. In seven of nine sites, toxicity of surface sediments differed from toxicity at levels beneath by 28 to 69%, in five instances underestimating toxicity (28 to 69%), and in two instances overestimating toxicity (44 to 56%). Multiple contaminants exceeded sediment quality guidelines and correlated positively with toxic responses within surface sediments (e.g., chromium, nickel, polycyclic aromatic hydrocarbon (PAH), total petroleum hydrocarbon). Use of an antibody-based PAH biosensor revealed that porewater PAH concentrations also increased with depth at most sites. This study informs future management decisions concerning the extent of impact to Bear Creek sediments, and demonstrates the benefits of a spatial approach, relying primarily on toxicity testing to assess sediment quality in a system with complex contaminant mixtures.

  16. The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein.

    PubMed Central

    Kristie, T M; LeBowitz, J H; Sharp, P A

    1989-01-01

    The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions. Images PMID:2556266

  17. The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein.

    PubMed

    Kristie, T M; LeBowitz, J H; Sharp, P A

    1989-12-20

    The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions.

  18. Analysis of Radar Images of Angkor, Cambodia

    NASA Technical Reports Server (NTRS)

    Freeman, Anthony; Hensley, Scott; Moore, Elizabeth

    2000-01-01

    During the 1996 AIRSAR Pacific Rim Deployment, data were collected over Angkor in Cambodia. The temples of Angkor date the succession of cities to the 9th-13th century AD, but little is known of its prehistoric habitation. A related area of archaeological debate has been the origin, spiritual meaning and use of the hydraulic constructions in the urban zone. The high resolution, multi-channel capability of AIRSAR, together with the unprecedentedly accurate topography provided by TOPSAR, offer identification and delineation of these features. Examples include previously unrecorded circular earthworks around circular village sites, detection of unrecorded earthwork dykes, reservoirs and canal features, and of temple sites located some distance from the main temple complex at Angkor.

  19. Informatics tools to improve clinical research study implementation.

    PubMed

    Brandt, Cynthia A; Argraves, Stephanie; Money, Roy; Ananth, Gowri; Trocky, Nina M; Nadkarni, Prakash M

    2006-04-01

    There are numerous potential sources of problems when performing complex clinical research trials. These issues are compounded when studies are multi-site and multiple personnel from different sites are responsible for varying actions from case report form design to primary data collection and data entry. We describe an approach that emphasizes the use of a variety of informatics tools that can facilitate study coordination, training, data checks and early identification and correction of faulty procedures and data problems. The paper focuses on informatics tools that can help in case report form design, procedures and training and data management. Informatics tools can be used to facilitate study coordination and implementation of clinical research trials.

  20. The Multi-Parameter Wireless Sensing System (MPwise): Its Description and Application to Earthquake Risk Mitigation.

    PubMed

    Boxberger, Tobias; Fleming, Kevin; Pittore, Massimiliano; Parolai, Stefano; Pilz, Marco; Mikulla, Stefan

    2017-10-20

    The Multi-Parameter Wireless Sensing (MPwise) system is an innovative instrumental design that allows different sensor types to be combined with relatively high-performance computing and communications components. These units, which incorporate off-the-shelf components, can undertake complex information integration and processing tasks at the individual unit or node level (when used in a network), allowing the establishment of networks that are linked by advanced, robust and rapid communications routing and network topologies. The system (and its predecessors) was originally designed for earthquake risk mitigation, including earthquake early warning (EEW), rapid response actions, structural health monitoring, and site-effect characterization. For EEW, MPwise units are capable of on-site, decentralized, independent analysis of the recorded ground motion and based on this, may issue an appropriate warning, either by the unit itself or transmitted throughout a network by dedicated alarming procedures. The multi-sensor capabilities of the system allow it to be instrumented with standard strong- and weak-motion sensors, broadband sensors, MEMS (namely accelerometers), cameras, temperature and humidity sensors, and GNSS receivers. In this work, the MPwise hardware, software and communications schema are described, as well as an overview of its possible applications. While focusing on earthquake risk mitigation actions, the aim in the future is to expand its capabilities towards a more multi-hazard and risk mitigation role. Overall, MPwise offers considerable flexibility and has great potential in contributing to natural hazard risk mitigation.

  1. The Multi-Parameter Wireless Sensing System (MPwise): Its Description and Application to Earthquake Risk Mitigation

    PubMed Central

    Boxberger, Tobias; Fleming, Kevin; Pittore, Massimiliano; Parolai, Stefano; Pilz, Marco; Mikulla, Stefan

    2017-01-01

    The Multi-Parameter Wireless Sensing (MPwise) system is an innovative instrumental design that allows different sensor types to be combined with relatively high-performance computing and communications components. These units, which incorporate off-the-shelf components, can undertake complex information integration and processing tasks at the individual unit or node level (when used in a network), allowing the establishment of networks that are linked by advanced, robust and rapid communications routing and network topologies. The system (and its predecessors) was originally designed for earthquake risk mitigation, including earthquake early warning (EEW), rapid response actions, structural health monitoring, and site-effect characterization. For EEW, MPwise units are capable of on-site, decentralized, independent analysis of the recorded ground motion and based on this, may issue an appropriate warning, either by the unit itself or transmitted throughout a network by dedicated alarming procedures. The multi-sensor capabilities of the system allow it to be instrumented with standard strong- and weak-motion sensors, broadband sensors, MEMS (namely accelerometers), cameras, temperature and humidity sensors, and GNSS receivers. In this work, the MPwise hardware, software and communications schema are described, as well as an overview of its possible applications. While focusing on earthquake risk mitigation actions, the aim in the future is to expand its capabilities towards a more multi-hazard and risk mitigation role. Overall, MPwise offers considerable flexibility and has great potential in contributing to natural hazard risk mitigation. PMID:29053608

  2. Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

    PubMed Central

    Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

    2015-01-01

    Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

  3. Excited state electron and energy relays in supramolecular dinuclear complexes revealed by ultrafast optical and X-ray transient absorption spectroscopy† †Electronic supplementary information (ESI) available: Synthesis schemes, experimental methods, NMR spectra, X-ray crystallographic information, emission spectra, cyclic voltammetry, electronic structure calculations, data analysis and numerical methods, and other additional figures. CCDC 1561879. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04055e

    PubMed Central

    Kohler, Lars; Hadt, Ryan G.; Zhang, Xiaoyi; Liu, Cunming

    2017-01-01

    The kinetics of photoinduced electron and energy transfer in a family of tetrapyridophenazine-bridged heteroleptic homo- and heterodinuclear copper(i) bis(phenanthroline)/ruthenium(ii) polypyridyl complexes were studied using ultrafast optical and multi-edge X-ray transient absorption spectroscopies. This work combines the synthesis of heterodinuclear Cu(i)–Ru(ii) analogs of the homodinuclear Cu(i)–Cu(i) targets with spectroscopic analysis and electronic structure calculations to first disentangle the dynamics at individual metal sites by taking advantage of the element and site specificity of X-ray absorption and theoretical methods. The excited state dynamical models developed for the heterodinuclear complexes are then applied to model the more challenging homodinuclear complexes. These results suggest that both intermetallic charge and energy transfer can be observed in an asymmetric dinuclear copper complex in which the ground state redox potentials of the copper sites are offset by only 310 meV. We also demonstrate the ability of several of these complexes to effectively and unidirectionally shuttle energy between different metal centers, a property that could be of great use in the design of broadly absorbing and multifunctional multimetallic photocatalysts. This work provides an important step toward developing both a fundamental conceptual picture and a practical experimental handle with which synthetic chemists, spectroscopists, and theoreticians may collaborate to engineer cheap and efficient photocatalytic materials capable of performing coulombically demanding chemical transformations. PMID:29629153

  4. Multi-spectroscopic and molecular modeling approaches to elucidate the binding interaction between bovine serum albumin and darunavir, a HIV protease inhibitor.

    PubMed

    Shi, Jie-Hua; Zhou, Kai-Li; Lou, Yan-Yue; Pan, Dong-Qi

    2018-01-05

    Darunavir (DRV), a second-generation HIV protease inhibitor, is widely used across the world as an important component of HIV therapy. The interaction of DRV with bovine serum albumin (BSA), a major carrier protein, has been studied under simulated physiological conditions (pH7.4) by multi-spectroscopic techniques in combination with molecular modeling. Fluorescence data revealed that the intrinsic fluorescence of BSA was quenched by DRV in terms of a static quenching procedure due to the formation of the DRV-BSA complex. The results indicated the presence of single weak affinity binding site (~10 3 M -1 , 310K) on protein. The thermodynamic parameters, namely enthalpy change (ΔH 0 ), entropy change (ΔS 0 ) and Gibbs free energy change (ΔG 0 ) were calculated, which signified that the binding reaction was spontaneous, the main binding forces were hydrogen bonding and van der Waals forces. Importantly, competitive binding experiments with three site probes, phenylbutazone (in sub-domain IIA, site I), ibuprofen (in sub-domain IIIA, site II) and artemether (in the interface between sub-domain IIA and IIB, site II'), suggested that DRV was preferentially bound to the hydrophobic cavity in site II' of BSA, and this finding was validated by the docking results. Additionally, synchronous fluorescence, three-dimensional fluorescence and Resonance Rayleigh Scattering (RRS) spectroscopy gave qualitative information on the conformational changes of BSA upon adding DRV, while quantitative data were obtained with Fourier transform infrared spectroscopy (FT-IR). Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Efficiency Evaluation of Food Waste Materials for the Removal of Metals and Metalloids from Complex Multi-Element Solutions

    PubMed Central

    Giuliano, Antonella; Astolfi, Maria Luisa; Congedo, Rossana; Masotti, Andrea; Canepari, Silvia

    2018-01-01

    Recent studies have shown the potential of food waste materials as low cost adsorbents for the removal of heavy metals and toxic elements from wastewater. However, the adsorption experiments have been performed in heterogeneous conditions, consequently it is difficult to compare the efficiency of the individual adsorbents. In this study, the adsorption capacities of 12 food waste materials were evaluated by comparing the adsorbents’ efficiency for the removal of 23 elements from complex multi-element solutions, maintaining homogeneous experimental conditions. The examined materials resulted to be extremely efficient for the adsorption of many elements from synthetic multi-element solutions as well as from a heavy metal wastewater. The 12 adsorbent surfaces were analyzed by Fourier transform infrared spectroscopy and showed different types and amounts of functional groups, which demonstrated to act as adsorption active sites for various elements. By multivariate statistical computations of the obtained data, the 12 food waste materials were grouped in five clusters characterized by different elements’ removal efficiency which resulted to be in correlation with the specific adsorbents’ chemical structures. Banana peel, watermelon peel and grape waste resulted the least selective and the most efficient food waste materials for the removal of most of the elements. PMID:29495363

  6. Efficiency Evaluation of Food Waste Materials for the Removal of Metals and Metalloids from Complex Multi-Element Solutions.

    PubMed

    Massimi, Lorenzo; Giuliano, Antonella; Astolfi, Maria Luisa; Congedo, Rossana; Masotti, Andrea; Canepari, Silvia

    2018-02-26

    Recent studies have shown the potential of food waste materials as low cost adsorbents for the removal of heavy metals and toxic elements from wastewater. However, the adsorption experiments have been performed in heterogeneous conditions, consequently it is difficult to compare the efficiency of the individual adsorbents. In this study, the adsorption capacities of 12 food waste materials were evaluated by comparing the adsorbents' efficiency for the removal of 23 elements from complex multi-element solutions, maintaining homogeneous experimental conditions. The examined materials resulted to be extremely efficient for the adsorption of many elements from synthetic multi-element solutions as well as from a heavy metal wastewater. The 12 adsorbent surfaces were analyzed by Fourier transform infrared spectroscopy and showed different types and amounts of functional groups, which demonstrated to act as adsorption active sites for various elements. By multivariate statistical computations of the obtained data, the 12 food waste materials were grouped in five clusters characterized by different elements' removal efficiency which resulted to be in correlation with the specific adsorbents' chemical structures. Banana peel, watermelon peel and grape waste resulted the least selective and the most efficient food waste materials for the removal of most of the elements.

  7. 03pd2227

    NASA Image and Video Library

    2003-07-23

    KENNEDY SPACE CENTER, FLA. – This view shows much of the Launch Complex 39 Area stretching beyond the Turn Basin in the foreground. The largest building is the 525-foot-tall Vehicle Assembly Building. In front of it is the Launch Control Center. Behind and to the left of the VAB are the Orbiter Processing Facility bays. At left are the Multi-Function Facility and Operations Support Building. At left of the Turn Basin is the Press Site, which comprises the NASA News Center, grandstand, TV studio and media buildings.

  8. High prevalence of daily and multi-site pain – a cross-sectional population-based study among 3000 Danish adolescents

    PubMed Central

    2013-01-01

    Background Daily pain and multi-site pain are both associated with reduction in work ability and health-related quality of life (HRQoL) among adults. However, no population-based studies have yet investigated the prevalence of daily and multi-site pain among adolescents and how these are associated with respondent characteristics. The purpose of this study was to investigate the prevalence of self-reported daily and multi-site pain among adolescents aged 12–19 years and associations of almost daily pain and multi-site pain with respondent characteristics (sex, age, body mass index, HRQoL and sports participation). Methods A population-based cross-sectional study was conducted among 4,007 adolescents aged 12–19 years in Denmark. Adolescents answered an online questionnaire during physical education lessons. The questionnaire contained a mannequin divided into 12 regions on which the respondents indicated their current pain sites and pain frequency (rarely, monthly, weekly, more than once per week, almost daily pain), characteristics, sports participation and HRQoL measured by the EuroQoL 5D. Multivariate regression was used to calculate the odds ratio for the association between almost daily pain, multi-site pain and respondent characteristics. Results The response rate was 73.7%. A total of 2,953 adolescents (62% females) answered the questionnaire. 33.3% reported multi-site pain (pain in >1 region) while 19.8% reported almost daily pain. 61% reported current pain in at least one region with knee and back pain being the most common sites. Female sex (OR: 1.35-1.44) and a high level of sports participation (OR: 1.51-2.09) were associated with increased odds of having almost daily pain and multi-site pain. Better EQ-5D score was associated with decreased odds of having almost daily pain or multi-site pain (OR: 0.92-0.94). Conclusion In this population-based cohort of school-attending Danish adolescents, nearly two out of three reported current pain and, on average, one out of three reported pain in more than one body region. Female sex, and high level of sports participation were associated with increased odds of having almost daily pain and multi-site pain. The study highlights an important health issue that calls for investigations to improve our understanding of adolescent pain and our capacity to prevent and treat this condition. PMID:24252440

  9. Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme

    NASA Astrophysics Data System (ADS)

    Patwardhan, Anjali A.

    The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized Cu(II) derivatives of the aminoglycosides, kanamycin A, tobramycin, neamine, kanamycin B, neomycin B, and paromomycin. The first three exhibit preferential and tight binding to Cu(II) as against neomycin B and kanamycin B and paromomycin. EPR of frozen solutions and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence co-reactants like hydrogen peroxide or ascorbic acid. Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific with C-4' H abstraction resulting in characteristic base propenal and nucleotide base products. Hydroxyl radicals generated are copper based and are generated in close proximity of the substrate. Hammerhead ribozymes are selectively hydrolyzed in the presence of divalent ions with Mg2+ being the metal ion of choice in vivo . Our studies with complex ions like cobalt hexaammine and fac-triamminetriaquochromium(III) establish outer sphere interactions of Mg2+ with the hammerhead in the catalytic site. There are two sets of sites, one structural and one catalytic. Complex ions in the catalytic site and divalent ions in the structural site result in a slow but active hammerhead ribozyme suggesting that the complex ions are not inhibitory, contrary to what was suggested previously.

  10. Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM)

    EPA Pesticide Factsheets

    The Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) provides detailed guidance on how to demonstrate that a site is in compliance with a radiation dose- or risk-based regulation.

  11. 77 FR 29701 - Impact of Construction (Under a Combined License) of New Nuclear Power Plant Units on Operating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... New Nuclear Power Plant Units on Operating Units at Multi-Unit Sites AGENCY: Nuclear Regulatory... construct and operate new nuclear power plants (NPPs) on multi-unit sites to provide an evaluation of the... License) of New Nuclear Power Plants on Operating Units at Multi-Unit Sites (Package). ML112630039 Federal...

  12. Joint explorative analysis of neuroreceptor subsystems in the human brain: application to receptor-transporter correlation using PET data.

    PubMed

    Cselényi, Zsolt; Lundberg, Johan; Halldin, Christer; Farde, Lars; Gulyás, Balázs

    2004-10-01

    Positron emission tomography (PET) has proved to be a highly successful technique in the qualitative and quantitative exploration of the human brain's neurotransmitter-receptor systems. In recent years, the number of PET radioligands, targeted to different neuroreceptor systems of the human brain, has increased considerably. This development paves the way for a simultaneous analysis of different receptor systems and subsystems in the same individual. The detailed exploration of the versatility of neuroreceptor systems requires novel technical approaches, capable of operating on huge parametric image datasets. An initial step of such explorative data processing and analysis should be the development of novel exploratory data-mining tools to gain insight into the "structure" of complex multi-individual, multi-receptor data sets. For practical reasons, a possible and feasible starting point of multi-receptor research can be the analysis of the pre- and post-synaptic binding sites of the same neurotransmitter. In the present study, we propose an unsupervised, unbiased data-mining tool for this task and demonstrate its usefulness by using quantitative receptor maps, obtained with positron emission tomography, from five healthy subjects on (pre-synaptic) serotonin transporters (5-HTT or SERT) and (post-synaptic) 5-HT(1A) receptors. Major components of the proposed technique include the projection of the input receptor maps to a feature space, the quasi-clustering and classification of projected data (neighbourhood formation), trans-individual analysis of neighbourhood properties (trajectory analysis), and the back-projection of the results of trajectory analysis to normal space (creation of multi-receptor maps). The resulting multi-receptor maps suggest that complex relationships and tendencies in the relationship between pre- and post-synaptic transporter-receptor systems can be revealed and classified by using this method. As an example, we demonstrate the regional correlation of the serotonin transporter-receptor systems. These parameter-specific multi-receptor maps can usefully guide the researchers in their endeavour to formulate models of multi-receptor interactions and changes in the human brain.

  13. Streamflow prediction using multi-site rainfall obtained from hydroclimatic teleconnection

    NASA Astrophysics Data System (ADS)

    Kashid, S. S.; Ghosh, Subimal; Maity, Rajib

    2010-12-01

    SummarySimultaneous variations in weather and climate over widely separated regions are commonly known as "hydroclimatic teleconnections". Rainfall and runoff patterns, over continents, are found to be significantly teleconnected, with large-scale circulation patterns, through such hydroclimatic teleconnections. Though such teleconnections exist in nature, it is very difficult to model them, due to their inherent complexity. Statistical techniques and Artificial Intelligence (AI) tools gain popularity in modeling hydroclimatic teleconnection, based on their ability, in capturing the complicated relationship between the predictors (e.g. sea surface temperatures) and predictand (e.g., rainfall). Genetic Programming is such an AI tool, which is capable of capturing nonlinear relationship, between predictor and predictand, due to its flexible functional structure. In the present study, gridded multi-site weekly rainfall is predicted from El Niño Southern Oscillation (ENSO) indices, Equatorial Indian Ocean Oscillation (EQUINOO) indices, Outgoing Longwave Radiation (OLR) and lag rainfall at grid points, over the catchment, using Genetic Programming. The predicted rainfall is further used in a Genetic Programming model to predict streamflows. The model is applied for weekly forecasting of streamflow in Mahanadi River, India, and satisfactory performance is observed.

  14. Biocatalytic site- and enantioselective oxidative dearomatization of phenols

    NASA Astrophysics Data System (ADS)

    Baker Dockrey, Summer A.; Lukowski, April L.; Becker, Marc R.; Narayan, Alison R. H.

    2018-02-01

    The biocatalytic transformations used by chemists are often restricted to simple functional-group interconversions. In contrast, nature has developed complexity-generating biocatalytic reactions within natural product pathways. These sophisticated catalysts are rarely employed by chemists, because the substrate scope, selectivity and robustness of these catalysts are unknown. Our strategy to bridge the gap between the biosynthesis and synthetic chemistry communities leverages the diversity of catalysts available within natural product pathways. Here we show that, starting from a suite of biosynthetic enzymes, catalysts with complementary substrate scope as well as selectivity can be identified. This strategy has been applied to the oxidative dearomatization of phenols, a chemical transformation that rapidly builds molecular complexity from simple starting materials and cannot be accomplished with high selectivity using existing catalytic methods. Using enzymes from biosynthetic pathways, we have successfully developed a method to produce ortho-quinol products with controlled site- and stereoselectivity. Furthermore, we have capitalized on the scalability and robustness of this method in gram-scale reactions as well as multi-enzyme and chemoenzymatic cascades.

  15. Data management integration for biomedical core facilities

    NASA Astrophysics Data System (ADS)

    Zhang, Guo-Qiang; Szymanski, Jacek; Wilson, David

    2007-03-01

    We present the design, development, and pilot-deployment experiences of MIMI, a web-based, Multi-modality Multi-Resource Information Integration environment for biomedical core facilities. This is an easily customizable, web-based software tool that integrates scientific and administrative support for a biomedical core facility involving a common set of entities: researchers; projects; equipments and devices; support staff; services; samples and materials; experimental workflow; large and complex data. With this software, one can: register users; manage projects; schedule resources; bill services; perform site-wide search; archive, back-up, and share data. With its customizable, expandable, and scalable characteristics, MIMI not only provides a cost-effective solution to the overarching data management problem of biomedical core facilities unavailable in the market place, but also lays a foundation for data federation to facilitate and support discovery-driven research.

  16. Economic and environmental optimization of a multi-site utility network for an industrial complex.

    PubMed

    Kim, Sang Hun; Yoon, Sung-Geun; Chae, Song Hwa; Park, Sunwon

    2010-01-01

    Most chemical companies consume a lot of steam, water and electrical resources in the production process. Given recent record fuel costs, utility networks must be optimized to reduce the overall cost of production. Environmental concerns must also be considered when preparing modifications to satisfy the requirements for industrial utilities, since wastes discharged from the utility networks are restricted by environmental regulations. Construction of Eco-Industrial Parks (EIPs) has drawn attention as a promising approach for retrofitting existing industrial parks to improve energy efficiency. The optimization of the utility network within an industrial complex is one of the most important undertakings to minimize energy consumption and waste loads in the EIP. In this work, a systematic approach to optimize the utility network of an industrial complex is presented. An important issue in the optimization of a utility network is the desire of the companies to achieve high profits while complying with the environmental regulations. Therefore, the proposed optimization was performed with consideration of both economic and environmental factors. The proposed approach consists of unit modeling using thermodynamic principles, mass and energy balances, development of a multi-period Mixed Integer Linear Programming (MILP) model for the integration of utility systems in an industrial complex, and an economic/environmental analysis of the results. This approach is applied to the Yeosu Industrial Complex, considering seasonal utility demands. The results show that both the total utility cost and waste load are reduced by optimizing the utility network of an industrial complex. 2009 Elsevier Ltd. All rights reserved.

  17. The Challenges and Benefits of Employing a Mobile Research Fellow to Facilitate Team Work on a Large, Interdisciplinary, Multi-Sited Project

    ERIC Educational Resources Information Center

    Sugden, Fraser; Punch, Samantha

    2014-01-01

    Over the last few years research funding has increasingly moved in favour of large, multi-partner, interdisciplinary and multi-site research projects. This article explores the benefits and challenges of employing a full-time research fellow to work across multiple field sites, with all the local research teams, on an international,…

  18. Simplifying the complexity surrounding ICU work processes--identifying the scope for information management in ICU settings.

    PubMed

    Munir, Samina K; Kay, Stephen

    2005-08-01

    A multi-site study, conducted in two English and two Danish intensive care units, investigates the complexity of work processes in intensive care, and the implications of this complexity for information management with regards to clinical information systems. Data were collected via observations, shadowing of clinical staff, interviews and questionnaires. The construction of role activity diagrams enabled the capture of critical care work processes. Upon analysing these diagrams, it was found that intensive care work processes consist of 'simplified-complexity', these processes are changed with the introduction of information systems for the everyday use and management of all clinical information. The prevailing notion of complexity surrounding critical care clinical work processes was refuted and found to be misleading; in reality, it is not the work processes that cause the complexity, the complexity is rooted in the way in which clinical information is used and managed. This study emphasises that the potential for clinical information systems that consider integrating all clinical information requirements is not only immense but also very plausible.

  19. Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex

    PubMed Central

    Kim, Kyung Rok; Park, Sang Ho; Kim, Hyoun Sook; Rhee, Kyung Hee; Kim, Byung-Gyu; Kim, Dae Gyu; Park, Mi Seul; Kim, Hyun-Jung; Kim, Sunghoon; Han, Byung Woo

    2013-01-01

    Human cytosolic aspartyl-tRNA synthetase (DRS) catalyzes the attachment of the amino acid aspartic acid to its cognate tRNA and it is a component of the multi-tRNA synthetase complex (MSC) which has been known to be involved in unexpected signaling pathways. Here, we report the crystal structure of DRS at a resolution of 2.25 Å. DRS is a homodimer with a dimer interface of 3750.5 Å2 which comprises 16.6% of the monomeric surface area. Our structure reveals the C-terminal end of the N-helix which is considered as a unique addition in DRS, and its conformation further supports the switching model of the N-helix for the transfer of tRNAAsp to elongation factor 1α. From our analyses of the crystal structure and post-translational modification of DRS, we suggest that the phosphorylation of Ser146 provokes the separation of DRS from the MSC and provides the binding site for an interaction partner with unforeseen functions. PMID:23609930

  20. Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex.

    PubMed

    Kim, Kyung Rok; Park, Sang Ho; Kim, Hyoun Sook; Rhee, Kyung Hee; Kim, Byung-Gyu; Kim, Dae Gyu; Park, Mi Seul; Kim, Hyun-Jung; Kim, Sunghoon; Han, Byung Woo

    2013-10-01

    Human cytosolic aspartyl-tRNA synthetase (DRS) catalyzes the attachment of the amino acid aspartic acid to its cognate tRNA and it is a component of the multi-tRNA synthetase complex (MSC) which has been known to be involved in unexpected signaling pathways. Here, we report the crystal structure of DRS at a resolution of 2.25 Å. DRS is a homodimer with a dimer interface of 3750.5 Å(2) which comprises 16.6% of the monomeric surface area. Our structure reveals the C-terminal end of the N-helix which is considered as a unique addition in DRS, and its conformation further supports the switching model of the N-helix for the transfer of tRNA(Asp) to elongation factor 1α. From our analyses of the crystal structure and post-translational modification of DRS, we suggest that the phosphorylation of Ser146 provokes the separation of DRS from the MSC and provides the binding site for an interaction partner with unforeseen functions. Copyright © 2013 Wiley Periodicals, Inc.

  1. Psychosocial stress and multi-site musculoskeletal pain: a cross-sectional survey of patient care workers.

    PubMed

    Sembajwe, Grace; Tveito, Torill Helene; Hopcia, Karen; Kenwood, Christopher; O'Day, Elizabeth Tucker; Stoddard, Anne M; Dennerlein, Jack T; Hashimoto, Dean; Sorensen, Glorian

    2013-03-01

    The aim of this study was to assess the relationship between psychosocial factors at work and multi-site musculoskeletal pain among patient care workers. In a survey of 1,572 workers from two hospitals, occupational psychosocial factors and health outcomes of workers with single and multi-site pain were evaluated using items from the Job Content Questionnaire that was designed to measure psychological demands, decision latitude, and social support. An adapted Nordic Questionnaire provided data on the musculoskeletal pain outcome. Covariates included body mass index, age, gender, and occupation. The analyses revealed statistically significant associations between psychosocial demands and multi-site musculoskeletal pain among patient care associates, nurses, and administrative personnel, both men and women. Supervisor support played a significant role for nurses and women. These results remained statistically significant after adjusting for covariates. These results highlight the associations between workplace psychosocial strain and multi-site musculoskeletal pain, setting the stage for future longitudinal explorations. Copyright 2013, SLACK Incorporated.

  2. Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders.

    PubMed

    Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; Penninx, Brenda W J H; Dekker, Joost

    2014-07-09

    Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain.

  3. Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders

    PubMed Central

    2014-01-01

    Background Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. Methods Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). Results In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. Conclusions Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain. PMID:25007969

  4. REVIEW OF MULTI-AGENCY RADIATION SURVEY & SITE INVESTIGATION MANUAL (MARSSIM) SUPPLEMENT: MULTI-AGENCY RADIATION SURVEY AND ASSESSMENT OF MATERIALS AND EQUIPMENT (MARSAME)

    EPA Science Inventory

    Radioactive materials have been produced, processed, used, and transported amongst thousands of sites throughout the United States. Owners and operators of these sites would like to determine if materials or equipment on these sites are contaminated with radioactive materials, i...

  5. Report on July 2015 Additional Protocol Coordinators Best Practices Workshop

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

    Gitau, Ernest T.N.; Burbank, Roberta L.; Finch, Valerie A.

    After 10 years of implementation experience, the Office of Nonproliferation and Arms Control (NPAC) within the Department of Energy/National Nuclear Security Administration (DOE/NNSA) conducted the Additional Protocol (AP) Coordinators Best Practices Workshop at Oak Ridge National Laboratory from July 29-30, 2015. The goal of this workshop was to identify implementation best practices, lessons learned, and compliance challenges from the various Additional Protocol Coordinators (APCs) at each laboratory in the DOE/NNSA complex and associated sites. The workshop provided the opportunity for participants to share their insights and establish networks that APCs can utilize to continue to discuss challenges (new and old),more » identify best practices, and enhance communication and coordination for reporting multi-lab research projects during review activities. Workshop participants included DOE/NNSA HQ, laboratory and site APCs, seasoned experts, members of the original implementation outreach team, and Field Element and site security representatives.« less

  6. Analytic hierarchy process-based approach for selecting a Pareto-optimal solution of a multi-objective, multi-site supply-chain planning problem

    NASA Astrophysics Data System (ADS)

    Ayadi, Omar; Felfel, Houssem; Masmoudi, Faouzi

    2017-07-01

    The current manufacturing environment has changed from traditional single-plant to multi-site supply chain where multiple plants are serving customer demands. In this article, a tactical multi-objective, multi-period, multi-product, multi-site supply-chain planning problem is proposed. A corresponding optimization model aiming to simultaneously minimize the total cost, maximize product quality and maximize the customer satisfaction demand level is developed. The proposed solution approach yields to a front of Pareto-optimal solutions that represents the trade-offs among the different objectives. Subsequently, the analytic hierarchy process method is applied to select the best Pareto-optimal solution according to the preferences of the decision maker. The robustness of the solutions and the proposed approach are discussed based on a sensitivity analysis and an application to a real case from the textile and apparel industry.

  7. Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis

    PubMed Central

    Cozens, Christopher

    2018-01-01

    Abstract Engineering proteins for designer functions and biotechnological applications almost invariably requires (or at least benefits from) multiple mutations to non-contiguous residues. Several methods for multiple site-directed mutagenesis exist, but there remains a need for fast and simple methods to efficiently introduce such mutations – particularly for generating large, high quality libraries for directed evolution. Here, we present Darwin Assembly, which can deliver high quality libraries of >108 transformants, targeting multiple (>10) distal sites with minimal wild-type contamination (<0.25% of total population) and which takes a single working day from purified plasmid to library transformation. We demonstrate its efficacy with whole gene codon reassignment of chloramphenicol acetyl transferase, mutating 19 codons in a single reaction in KOD DNA polymerase and generating high quality, multiple-site libraries in T7 RNA polymerase and Tgo DNA polymerase. Darwin Assembly uses commercially available enzymes, can be readily automated, and offers a cost-effective route to highly complex and customizable library generation. PMID:29409059

  8. Temporary site selection and decision-making methods: a case study of Tehran, Iran.

    PubMed

    Omidvar, Babak; Baradaran-Shoraka, Mohammad; Nojavan, Mehdi

    2013-07-01

    Decisions on selecting an appropriate site for temporary shelter used to be taken in a limited amount of time after a disaster. The need for a systematic method in this area inspired the MADM (multi-attribute decision making) for complex disaster management decisions. This research proposes a model for appropriate and systematic site selection for temporary shelters, before an earthquake, using a geographical information system and MADM based on an earthquake damage assessment. After the effective criteria for site selection of temporary shelters are determined, the geographical layers of these criteria are prepared for Municipal District No.1 of Greater Tehran, the capital of Iran. Given these attributes and the required shelter area (415-610 hectares), 14 zones are proposed initially. Various MADM methods are used for the final selection. The mean of the aggregated ranking results are determined, and 10 of the 14 initial zones are ranked. © 2013 The Author(s). Journal compilation © Overseas Development Institute, 2013.

  9. Improved multi-objective ant colony optimization algorithm and its application in complex reasoning

    NASA Astrophysics Data System (ADS)

    Wang, Xinqing; Zhao, Yang; Wang, Dong; Zhu, Huijie; Zhang, Qing

    2013-09-01

    The problem of fault reasoning has aroused great concern in scientific and engineering fields. However, fault investigation and reasoning of complex system is not a simple reasoning decision-making problem. It has become a typical multi-constraint and multi-objective reticulate optimization decision-making problem under many influencing factors and constraints. So far, little research has been carried out in this field. This paper transforms the fault reasoning problem of complex system into a paths-searching problem starting from known symptoms to fault causes. Three optimization objectives are considered simultaneously: maximum probability of average fault, maximum average importance, and minimum average complexity of test. Under the constraints of both known symptoms and the causal relationship among different components, a multi-objective optimization mathematical model is set up, taking minimizing cost of fault reasoning as the target function. Since the problem is non-deterministic polynomial-hard(NP-hard), a modified multi-objective ant colony algorithm is proposed, in which a reachability matrix is set up to constrain the feasible search nodes of the ants and a new pseudo-random-proportional rule and a pheromone adjustment mechinism are constructed to balance conflicts between the optimization objectives. At last, a Pareto optimal set is acquired. Evaluation functions based on validity and tendency of reasoning paths are defined to optimize noninferior set, through which the final fault causes can be identified according to decision-making demands, thus realize fault reasoning of the multi-constraint and multi-objective complex system. Reasoning results demonstrate that the improved multi-objective ant colony optimization(IMACO) can realize reasoning and locating fault positions precisely by solving the multi-objective fault diagnosis model, which provides a new method to solve the problem of multi-constraint and multi-objective fault diagnosis and reasoning of complex system.

  10. Ethics Review for a Multi-Site Project Involving Tribal Nations in the Northern Plains.

    PubMed

    Angal, Jyoti; Petersen, Julie M; Tobacco, Deborah; Elliott, Amy J

    2016-04-01

    Increasingly, Tribal Nations are forming ethics review panels, which function separately from institutional review boards (IRBs). The emergence of strong community representation coincides with a widespread effort supported by the U.S. Department of Health & Human Services and other federal agencies to establish a single IRB for all multi-site research. This article underscores the value of a tribal ethics review board and describes the tribal oversight for the Safe Passage Study-a multi-site, community-based project in the Northern Plains. Our experience demonstrates the benefits of tribal ethics review and makes a strong argument for including tribal oversight in future regulatory guidance for multi-site, community-based research. © The Author(s) 2016.

  11. Evapotranspiration response to multi-year dry periods in the semi-arid western United States

    NASA Astrophysics Data System (ADS)

    Rungee, J. P., II; Bales, R. C.

    2017-12-01

    Analysis of measured evapotranspiration shows multi-year regolith water storage can support evapotranspiration for years into a multi-year dry period. Measurements at 25 flux-tower sites in the semi-arid western United States, distributed across five primary land-cover types, show both resilience and vulnerability to multi-year dry periods. Average evapotranspiration ranged from about 700+200 mm per water year (October-September) in evergreen needleleaf forests to 350+150 mm per water year in grasslands and open shrublands. On average, in California's Mediterranean climate almost half of the water-year evapotranspiration is supported by seasonal and/or multi-year regolith water storage, compared to a characteristic 20 to 30 percent value of energy-limited and inland sites. Below 35oN latitude, water-year evapotranspiration exceeded estimated precipitation in over half of the years on record. For non-energy-limited sites, water-year evapotranspiration increased with precipitation up to a maximum water-year evapotranspiration value of about 900, 750, 600, 425 and 300 mm per water year for evergreen needleleaf forests, mixed forests, woody savannas, grasslands and open shrublands, respectively. There were 15 multi-year dry periods on record that exhibited either an attenuation in evapotranspiration, defined as an annual value below 80% of the wet-year average, or withdrawal from multi-year storage. A multi-year dry period was defined as three or more consecutive water years in which all water-year precipitation values and the mean period value were in the lower 50 and 35 percent of the historical record, respectively. For sites exhibiting evapotranspiration attenuation, resistance to multi-year dry periods ranged from 9 to 49 months, drafting as much as 444 mm of regolith storage. At some mountain sites regolith storage provided up to 678 mm, almost the equivalent of the average water-year evapotranspiration for these sites, over the extent of the multi-year dry period.

  12. What qualitative research can contribute to a randomized controlled trial of a complex community intervention.

    PubMed

    Nelson, Geoffrey; Macnaughton, Eric; Goering, Paula

    2015-11-01

    Using the case of a large-scale, multi-site Canadian Housing First research demonstration project for homeless people with mental illness, At Home/Chez Soi, we illustrate the value of qualitative methods in a randomized controlled trial (RCT) of a complex community intervention. We argue that quantitative RCT research can neither capture the complexity nor tell the full story of a complex community intervention. We conceptualize complex community interventions as having multiple phases and dimensions that require both RCT and qualitative research components. Rather than assume that qualitative research and RCTs are incommensurate, a more pragmatic mixed methods approach was used, which included using both qualitative and quantitative methods to understand program implementation and outcomes. At the same time, qualitative research was used to examine aspects of the intervention that could not be understood through the RCT, such as its conception, planning, sustainability, and policy impacts. Through this example, we show how qualitative research can tell a more complete story about complex community interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Fair comparison of complexity between a multi-band CAP and DMT for data center interconnects.

    PubMed

    Wei, J L; Sanchez, C; Giacoumidis, E

    2017-10-01

    We present, to the best of our knowledge, the first known detailed analysis and fair comparison of complexity of a 56 Gb/s multi-band carrierless amplitude and phase (CAP) and discrete multi-tone (DMT) over 80 km dispersion compensation fiber-free single-mode fiber links based on intensity modulation and direct detection for data center interconnects. We show that the matched finite impulse response filters and inverse fast Fourier transform (IFFT)/FFT take the majority of the complexity of the multi-band CAP and DMT, respectively. The choice of the multi-band CAP sub-band count and the DMT IFFT/FFT size makes significant impact on the system complexity or performance, and trade-off must be considered.

  14. Decision aids for multiple-decision disease management as affected by weather input errors.

    PubMed

    Pfender, W F; Gent, D H; Mahaffee, W F; Coop, L B; Fox, A D

    2011-06-01

    Many disease management decision support systems (DSSs) rely, exclusively or in part, on weather inputs to calculate an indicator for disease hazard. Error in the weather inputs, typically due to forecasting, interpolation, or estimation from off-site sources, may affect model calculations and management decision recommendations. The extent to which errors in weather inputs affect the quality of the final management outcome depends on a number of aspects of the disease management context, including whether management consists of a single dichotomous decision, or of a multi-decision process extending over the cropping season(s). Decision aids for multi-decision disease management typically are based on simple or complex algorithms of weather data which may be accumulated over several days or weeks. It is difficult to quantify accuracy of multi-decision DSSs due to temporally overlapping disease events, existence of more than one solution to optimizing the outcome, opportunities to take later recourse to modify earlier decisions, and the ongoing, complex decision process in which the DSS is only one component. One approach to assessing importance of weather input errors is to conduct an error analysis in which the DSS outcome from high-quality weather data is compared with that from weather data with various levels of bias and/or variance from the original data. We illustrate this analytical approach for two types of DSS, an infection risk index for hop powdery mildew and a simulation model for grass stem rust. Further exploration of analysis methods is needed to address problems associated with assessing uncertainty in multi-decision DSSs.

  15. An investigation of site effeects on roadside measurement of truck noise

    DOT National Transportation Integrated Search

    1977-01-31

    Multi-microphone measurements of the passby noise emissions from three dedicated multi-axle trucks and from transient trucking were made at nine highway sites and one standard (SAE-J366b) measuring site. Measurements were made in and around Fort Wayn...

  16. Saccharification efficiencies of multi-enzyme complexes produced by aerobic fungi.

    PubMed

    Badhan, Ajay; Huang, Jiangli; Wang, Yuxi; Abbott, D Wade; Di Falco, Marcos; Tsang, Adrian; McAllister, Tim

    2018-05-24

    In the present study, we have characterized high molecular weight multi-enzyme complexes in two commercial enzymes produced by Trichoderma reesei (Spezyme CP) and Penicillium funiculosum (Accellerase XC). We successfully identified 146-1000 kDa complexes using Blue native polyacrylamide gel electrophoresis (BN-PAGE) to fractionate the protein profile in both preparations. Identified complexes dissociated into lower molecular weight constituents when loaded on SDS PAGE. Unfolding of the secondary structure of multi-enzyme complexes with trimethylamine (pH >10) suggested that they were not a result of unspecific protein aggregation. Cellulase (CMCase) profiles of extracts of BN-PAGE fractionated protein bands confirmed cellulase activity within the multi-enzyme complexes. A microassay was used to identify protein bands that promoted high levels of glucose release from barley straw. Those with high saccharification yield were subjected to LC-MS analysis to identify the principal enzymatic activities responsible. The results suggest that secretion of proteins by aerobic fungi leads to the formation of high molecular weight multi-enzyme complexes that display activity against carboxymethyl cellulose and barley straw. Copyright © 2018. Published by Elsevier B.V.

  17. A modular (almost) automatic set-up for elastic multi-tenants cloud (micro)infrastructures

    NASA Astrophysics Data System (ADS)

    Amoroso, A.; Astorino, F.; Bagnasco, S.; Balashov, N. A.; Bianchi, F.; Destefanis, M.; Lusso, S.; Maggiora, M.; Pellegrino, J.; Yan, L.; Yan, T.; Zhang, X.; Zhao, X.

    2017-10-01

    An auto-installing tool on an usb drive can allow for a quick and easy automatic deployment of OpenNebula-based cloud infrastructures remotely managed by a central VMDIRAC instance. A single team, in the main site of an HEP Collaboration or elsewhere, can manage and run a relatively large network of federated (micro-)cloud infrastructures, making an highly dynamic and elastic use of computing resources. Exploiting such an approach can lead to modular systems of cloud-bursting infrastructures addressing complex real-life scenarios.

  18. Cohort Selection and Management Application Leveraging Standards-based Semantic Interoperability and a Groovy DSL

    PubMed Central

    Bucur, Anca; van Leeuwen, Jasper; Chen, Njin-Zu; Claerhout, Brecht; de Schepper, Kristof; Perez-Rey, David; Paraiso-Medina, Sergio; Alonso-Calvo, Raul; Mehta, Keyur; Krykwinski, Cyril

    2016-01-01

    This paper describes a new Cohort Selection application implemented to support streamlining the definition phase of multi-centric clinical research in oncology. Our approach aims at both ease of use and precision in defining the selection filters expressing the characteristics of the desired population. The application leverages our standards-based Semantic Interoperability Solution and a Groovy DSL to provide high expressiveness in the definition of filters and flexibility in their composition into complex selection graphs including splits and merges. Widely-adopted ontologies such as SNOMED-CT are used to represent the semantics of the data and to express concepts in the application filters, facilitating data sharing and collaboration on joint research questions in large communities of clinical users. The application supports patient data exploration and efficient collaboration in multi-site, heterogeneous and distributed data environments. PMID:27570644

  19. Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

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

    Zheng, Wei; NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032; Li, Juan

    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3more » μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.« less

  20. Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate.

    PubMed

    Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L; Lata, James P; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M; Bergkvist, Magnus; Sherwood, Robert W; Zhang, Sheng; Travis, Alexander J

    2017-01-02

    For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Biomimicry promotes the efficiency of a 10-step sequential enzymatic reaction on nanoparticles, converting glucose to lactate

    PubMed Central

    Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L.; Lata, James P.; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M.; Bergkvist, Magnus; Sherwood, Robert W.; Zhang, Sheng; Travis, Alexander J.

    2016-01-01

    For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. PMID:27901298

  2. Integrating ecosystems measurements from multiple eddy-covariance sites to a simple model of ecosystem process - Are there possibilities for a uniform model calibration?

    NASA Astrophysics Data System (ADS)

    Minunno, Francesco; Peltoniemi, Mikko; Launiainen, Samuli; Mäkelä, Annikki

    2014-05-01

    Biogeochemical models quantify the material and energy flux exchanges between biosphere, atmosphere and soil, however there is still considerable uncertainty underpinning model structure and parametrization. The increasing availability of data from of multiple sources provides useful information for model calibration and validation at different space and time scales. We calibrated a simplified ecosystem process model PRELES to data from multiple sites. In this work we had the following objective: to compare a multi-site calibration and site-specific calibrations, in order to test if PRELES is a model of general applicability, and to test how well one parameterization can predict ecosystem fluxes. Model calibration and evaluation were carried out by the means of the Bayesian method; Bayesian calibration (BC) and Bayesian model comparison (BMC) were used to quantify the uncertainty in model parameters and model structure. Evapotranspiration (ET) and gross primary production (GPP) measurements collected in 9 sites of Finland and Sweden were used in the study; half dataset was used for model calibrations and half for the comparative analyses. 10 BCs were performed; the model was independently calibrated for each of the nine sites (site-specific calibrations) and a multi-site calibration was achieved using the data from all the sites in one BC. Then 9 BMCs were carried out, one for each site, using output from the multi-site and the site-specific versions of PRELES. Similar estimates were obtained for the parameters at which model outputs are most sensitive. Not surprisingly, the joint posterior distribution achieved through the multi-site calibration was characterized by lower uncertainty, because more data were involved in the calibration process. No significant differences were encountered in the prediction of the multi-site and site-specific versions of PRELES, and after BMC, we concluded that the model can be reliably used at regional scale to simulate carbon and water fluxes of Boreal forests. Despite being a simple model, PRELES provided good estimates of GPP and ET; only for one site PRELES multi-site version underestimated water fluxes. Our study implies convergence of GPP and water processes in boreal zone to the extent that their plausible prediction is possible with a simple model using global parameterization.

  3. A Hierarchical Modeling Approach to Data Analysis and Study Design in a Multi-Site Experimental fMRI Study

    ERIC Educational Resources Information Center

    Zhou, Bo; Konstorum, Anna; Duong, Thao; Tieu, Kinh H.; Wells, William M.; Brown, Gregory G.; Stern, Hal S.; Shahbaba, Babak

    2013-01-01

    We propose a hierarchical Bayesian model for analyzing multi-site experimental fMRI studies. Our method takes the hierarchical structure of the data (subjects are nested within sites, and there are multiple observations per subject) into account and allows for modeling between-site variation. Using posterior predictive model checking and model…

  4. Solution structure of the core SMN–Gemin2 complex

    PubMed Central

    Sarachan, Kathryn L.; Valentine, Kathleen G.; Gupta, Kushol; Moorman, Veronica R.; Gledhill, John M.; Bernens, Matthew; Tommos, Cecilia; Wand, A. Joshua; Van Duyne, Gregory D.

    2012-01-01

    In humans, assembly of spliceosomal snRNPs (small nuclear ribonucleoproteins) begins in the cytoplasm where the multi-protein SMN (survival of motor neuron) complex mediates the formation of a seven-membered ring of Sm proteins on to a conserved site of the snRNA (small nuclear RNA). The SMN complex contains the SMN protein Gemin2 and several additional Gemins that participate in snRNP biosynthesis. SMN was first identified as the product of a gene found to be deleted or mutated in patients with the neurodegenerative disease SMA (spinal muscular atrophy), the leading genetic cause of infant mortality. In the present study, we report the solution structure of Gemin2 bound to the Gemin2-binding domain of SMN determined by NMR spectroscopy. This complex reveals the structure of Gemin2, how Gemin2 binds to SMN and the roles of conserved SMN residues near the binding interface. Surprisingly, several conserved SMN residues, including the sites of two SMA patient mutations, are not required for binding to Gemin2. Instead, they form a conserved SMN/Gemin2 surface that may be functionally important for snRNP assembly. The SMN–Gemin2 structure explains how Gemin2 is stabilized by SMN and establishes a framework for structure–function studies to investigate snRNP biogenesis as well as biological processes involving Gemin2 that do not involve snRNP assembly. PMID:22607171

  5. Binding of RNA by the Nucleoproteins of Influenza Viruses A and B

    PubMed Central

    Labaronne, Alice; Swale, Christopher; Monod, Alexandre; Schoehn, Guy; Crépin, Thibaut; Ruigrok, Rob W. H.

    2016-01-01

    This paper describes a biochemical study for making complexes between the nucleoprotein of influenza viruses A and B (A/NP and B/NP) and small RNAs (polyUC RNAs from 5 to 24 nucleotides (nt)), starting from monomeric proteins. We used negative stain electron microscopy, size exclusion chromatography-multi-angle laser light scattering (SEC-MALLS) analysis, and fluorescence anisotropy measurements to show how the NP-RNA complexes evolve. Both proteins make small oligomers with 24-nt RNAs, trimers for A/NP, and dimers, tetramers, and larger complexes for B/NP. With shorter RNAs, the affinities of NP are all in the same range at 50 mM NaCl, showing that the RNAs bind on the same site. The affinity of B/NP for a 24-nt RNA does not change with salt. However, the affinity of A/NP for a 24-nt RNA is lower at 150 and 300 mM NaCl, suggesting that the RNA binds to another site, either on the same protomer or on a neighbour protomer. For our fluorescence anisotropy experiments, we used 6-fluorescein amidite (FAM)-labelled RNAs. By using a (UC)6-FAM3′ RNA with 150 mM NaCl, we observed an interesting phenomenon that gives macromolecular complexes similar to the ribonucleoprotein particles purified from the viruses. PMID:27649229

  6. Network cyberinfrastructure as a shared platform to support multi-site research

    USDA-ARS?s Scientific Manuscript database

    Multi-site research across the Long-term Agroecosystem Research (LTAR) network requires access to data and information. We present some existing examples where you can get data from across the network and summarize the rich inventory of measurements taken across LTAR sites. But data management suppo...

  7. Multi-site evaluation of IKONOS data for classification of tropical coral reef environments

    USGS Publications Warehouse

    Andrefouet, S.; Kramer, Philip; Torres-Pulliza, D.; Joyce, K.E.; Hochberg, E.J.; Garza-Perez, R.; Mumby, P.J.; Riegl, Bernhard; Yamano, H.; White, W.H.; Zubia, M.; Brock, J.C.; Phinn, S.R.; Naseer, A.; Hatcher, B.G.; Muller-Karger, F. E.

    2003-01-01

    Ten IKONOS images of different coral reef sites distributed around the world were processed to assess the potential of 4-m resolution multispectral data for coral reef habitat mapping. Complexity of reef environments, established by field observation, ranged from 3 to 15 classes of benthic habitats containing various combinations of sediments, carbonate pavement, seagrass, algae, and corals in different geomorphologic zones (forereef, lagoon, patch reef, reef flats). Processing included corrections for sea surface roughness and bathymetry, unsupervised or supervised classification, and accuracy assessment based on ground-truth data. IKONOS classification results were compared with classified Landsat 7 imagery for simple to moderate complexity of reef habitats (5-11 classes). For both sensors, overall accuracies of the classifications show a general linear trend of decreasing accuracy with increasing habitat complexity. The IKONOS sensor performed better, with a 15-20% improvement in accuracy compared to Landsat. For IKONOS, overall accuracy was 77% for 4-5 classes, 71% for 7-8 classes, 65% in 9-11 classes, and 53% for more than 13 classes. The Landsat classification accuracy was systematically lower, with an average of 56% for 5-10 classes. Within this general trend, inter-site comparisons and specificities demonstrate the benefits of different approaches. Pre-segmentation of the different geomorphologic zones and depth correction provided different advantages in different environments. Our results help guide scientists and managers in applying IKONOS-class data for coral reef mapping applications. ?? 2003 Elsevier Inc. All rights reserved.

  8. Fluorescence studies with DNA probes: dynamic aspects of DNA structure and DNA-protein interactions

    NASA Astrophysics Data System (ADS)

    Millar, David P.; Carver, Theodore E.

    1994-08-01

    Time-resolved fluorescence measurements of optical probes incorporated at specific sites in DNA provides a new approach to studies of DNA structure and DNA:protein interactions. This approach can be used to study complex multi-state behavior, such as the folding of DNA into alternative higher order structures or the transfer of DNA between multiple binding sites on a protein. In this study, fluorescence anisotropy decay of an internal dansyl probe attached to 17/27-mer oligonucleotides was used to monitor the distribution of DNA 3' termini bound at either the polymerase of 3' to 5' exonuclease sites of the Klenow fragment of DNA polymerase I. Partitioning of the primer terminus between the two active sites of the enzyme resulted in a heterogeneous probe environment, reflected in the associative behavior of the fluorescence anisotropy decay. Analysis of the anisotropy decay with a two state model of solvent-exposed and protein-associated dansyl probes was used to determine the fraction of DNA bound at each site. We examined complexes of Klenow fragment with DNAs containing various base mismatches. Single mismatches at the primer terminus caused a 3-fold increase in the equilibrium partitioning of DNA into the exonuclease site, while two or more consecutive G:G mismatches caused the DNA to bind exclusively at the exonuclease site, with a partitioning constant at least 250- fold greater than that of the corresponding matched DNA sequence. Internal single mismatches located up to four bases from the primer terminus produced larger effects than the same mismatch at the primer terminus. These results provide insight into the recognition mechanisms that enable DNA polymerases to proofread misincorporated bases during DNA replication.

  9. A guide to multi-centre ethics for surgical research in Australia and New Zealand.

    PubMed

    Boult, Maggi; Fitzpatrick, Kate; Maddern, Guy; Fitridge, Robert

    2011-03-01

    This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

  10. An evaluation of a silicone adhesive shaped heel dressing.

    PubMed

    Hampton, Sylvie

    Tissue breakdown is complex and involves many factors. Pressure ulcer development in the heels is subject to extrinsic factors such as pressure, shear, friction and moisture. The heels are the most common sites for friction and shear damage, which can lead to blistering, skin erosion and tissue breakdown (Grey et al, 2006). To address the issues of wounds that are painful on dressing removal and friable skin, Smith & Nephew has introduced a soft silicone adhesive dressing to its Allevyn dressing range. Silicone does not adhere to wounded areas and can be removed gently without trauma to the periwound area. This paper discusses the findings of a 20-patient multi-site evaluation examining the performance and acceptability of Allevyn Gentle Border Heel dressing in the management of heel wounds.

  11. Binding of copper to lysozyme: Spectroscopic, isothermal titration calorimetry and molecular docking studies

    NASA Astrophysics Data System (ADS)

    Jing, Mingyang; Song, Wei; Liu, Rutao

    2016-07-01

    Although copper is essential to all living organisms, its potential toxicity to human health have aroused wide concerns. Previous studies have reported copper could alter physical properties of lysozyme. The direct binding of copper with lysozyme might induce the conformational and functional changes of lysozyme and then influence the body's resistance to bacterial attack. To better understand the potential toxicity and toxic mechanisms of copper, the interaction of copper with lysozyme was investigated by biophysical methods including multi-spectroscopic measurements, isothermal titration calorimetry (ITC), molecular docking study and enzyme activity assay. Multi-spectroscopic measurements proved that copper quenched the intrinsic fluorescence of lysozyme in a static process accompanied by complex formation and conformational changes. The ITC results indicated that the binding interaction was a spontaneous process with approximately three thermodynamical binding sites at 298 K and the hydrophobic force is the predominant driven force. The enzyme activity was obviously inhibited by the addition of copper with catalytic residues Glu 35 and Asp 52 locating at the binding sites. This study helps to elucidate the molecular mechanism of the interaction between copper and lysozyme and provides reference for toxicological studies of copper.

  12. Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

    PubMed Central

    Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

    2010-01-01

    The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

  13. Structural modelling and molecular dynamics of a multi-stress responsive WRKY TF-DNA complex towards elucidating its role in stress signalling mechanisms in chickpea.

    PubMed

    Konda, Aravind Kumar; Farmer, Rohit; Soren, Khela Ram; P S, Shanmugavadivel; Setti, Aravind

    2017-07-28

    Chickpea is a premier food legume crop with high nutritional quality and attains prime importance in the current era of 795 million people being undernourished worldwide. Chickpea production encounters setbacks due to various stresses and understanding the role of key transcription factors (TFs) involved in multiple stresses becomes inevitable. We have recently identified a multi-stress responsive WRKY TF in chickpea. The present study was conducted to predict the structure of WRKY TF to identify the DNA-interacting residues and decipher DNA-protein interactions. Comparative modelling approach produced 3D model of the WRKY TF with good stereochemistry, local/global quality and further revealed W19, R20, K21, and Y22 motifs within a vicinity of 5 Å to the DNA amongst R18, G23, Q24, K25, Y36, Y37, R38 and K47 and these positions were equivalent to the 2LEX WRKY domain of Arabidopsis. Molecular simulations analysis of reference protein -PDB ID 2LEX, along with Car-WRKY TF modelled structure with the DNA coordinates derived from PDB ID 2LEX and docked using HADDOCK were executed. Root Mean Square (RMS) Deviation and RMS Fluctuation values yielded consistently stable trajectories over 50 ns simulation. Strengthening the obtained results, neither radius of gyration, distance and total energy showed any signs of DNA-WRKY complex falling apart nor any significant dissociation event over 50 ns run. Therefore, the study provides first insights into the structural properties of multi-stress responsive WRKY TF-DNA complex in chickpea, enabling genome wide identification of TF binding sites and thereby deciphers their gene regulatory networks.

  14. Cosmetic outcomes of laparoendoscopic single-site hysterectomy compared with multi-port surgery: randomized controlled trial.

    PubMed

    Song, Taejong; Cho, Juhee; Kim, Tae-Joong; Kim, Im-Ryung; Hahm, Tae Soo; Kim, Byoung-Gie; Bae, Duk-Soo

    2013-01-01

    To compare cosmetic satisfaction with laparoendoscopic single-site surgery (LESS) compared with multi-port surgery. Randomized controlled trial (Canadian Task Force classification I). University hospital. Twenty women who underwent laparoscopically-assisted vaginal hysterectomy (LAVH) via LESS or multi-port surgery. Laparoendoscopic single-site surgery or multi-port surgery. Cosmetic satisfaction was assessed using the Body Image Questionnaire at baseline and at 1, 4, and 24 weeks after surgery. Of the 20 LESS procedures, 1 was converted to multi-port surgery because of severe adhesions, and 1 woman assigned to undergo multi-port surgery was lost to follow-up. The 2 surgery groups did not differ in clinical demographic data and surgical results or postoperative pain scores at 12, 24, and 36 hours. Compared with the multi-port group, the LESS group reported significantly higher cosmetic satisfaction at 1, 4, and 24 weeks after surgery (p < .01). Compared with multi-port surgery, LESS is not only a feasible approach with comparable operative outcomes but also has an advantage insofar as cosmetic outcome. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

  15. Improving Lidar-based Aboveground Biomass Estimation with Site Productivity for Central Hardwood Forests, USA

    NASA Astrophysics Data System (ADS)

    Shao, G.; Gallion, J.; Fei, S.

    2016-12-01

    Sound forest aboveground biomass estimation is required to monitor diverse forest ecosystems and their impacts on the changing climate. Lidar-based regression models provided promised biomass estimations in most forest ecosystems. However, considerable uncertainties of biomass estimations have been reported in the temperate hardwood and hardwood-dominated mixed forests. Varied site productivities in temperate hardwood forests largely diversified height and diameter growth rates, which significantly reduced the correlation between tree height and diameter at breast height (DBH) in mature and complex forests. It is, therefore, difficult to utilize height-based lidar metrics to predict DBH-based field-measured biomass through a simple regression model regardless the variation of site productivity. In this study, we established a multi-dimension nonlinear regression model incorporating lidar metrics and site productivity classes derived from soil features. In the regression model, lidar metrics provided horizontal and vertical structural information and productivity classes differentiated good and poor forest sites. The selection and combination of lidar metrics were discussed. Multiple regression models were employed and compared. Uncertainty analysis was applied to the best fit model. The effects of site productivity on the lidar-based biomass model were addressed.

  16. Multi-Sited Ethnography and the Field of Educational Research

    ERIC Educational Resources Information Center

    Pierides, Dean

    2010-01-01

    This paper responds to the challenge of how educational research might be practised in a contemporary world that is no longer necessarily organised by nearness and unity. Focusing on ethnography, it argues for what a multi-sited imaginary contributes to research in the field of education. By giving prominence to the notion of multi-sited…

  17. Interdisciplinary Matchmaking: Choosing Collaborators by Skill, Acquaintance and Trust

    NASA Astrophysics Data System (ADS)

    Hupa, Albert; Rzadca, Krzysztof; Wierzbicki, Adam; Datta, Anwitaman

    Social networks are commonly used to enhance recommender systems. Most of such systems recommend a single resource or a person. However, complex problems or projects usually require a team of experts that must work together on a solution. Team recommendation is much more challenging, mostly because of the complex interpersonal relations between members. This chapter presents fundamental concepts on how to score a team based on members' social context and their suitability for a particular project. We represent the social context of an individual as a three-dimensional social network (3DSN) composed of a knowledge dimension expressing skills, a trust dimension and an acquaintance dimension. Dimensions of a 3DSN are used to mathematically formalize the criteria for prediction of the team's performance. We use these criteria to formulate the team recommendation problem as a multi-criteria optimization problem. We demonstrate our approach on empirical data crawled from two web2.0 sites: onephoto.net and a social networking site. We construct 3DSNs and analyze properties of team's performance criteria.

  18. Assembling the Tat protein translocase

    PubMed Central

    Alcock, Felicity; Stansfeld, Phillip J; Basit, Hajra; Habersetzer, Johann; Baker, Matthew AB; Palmer, Tracy; Wallace, Mark I; Berks, Ben C

    2016-01-01

    The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, molecular simulations, and experimentation to define the interactions between the Tat proteins of Escherichia coli at molecular-level resolution. In the TatBC receptor complex the transmembrane helix of each TatB molecule is sandwiched between two TatC molecules, with one of the inter-subunit interfaces incorporating a functionally important cluster of interacting polar residues. Unexpectedly, we find that TatA also associates with TatC at the polar cluster site. Our data provide a structural model for assembly of the active Tat translocase in which substrate binding triggers replacement of TatB by TatA at the polar cluster site. Our work demonstrates the power of co-evolution analysis to predict protein interfaces in multi-subunit complexes. DOI: http://dx.doi.org/10.7554/eLife.20718.001 PMID:27914200

  19. Utilization of charge-transfer complexation for the detection of carcinogenic substances in foods: Spectroscopic characterization of ethyl carbamate with some traditional π-acceptors

    NASA Astrophysics Data System (ADS)

    Adam, Abdel Majid A.; Refat, Moamen S.; Saad, Hosam A.

    2013-04-01

    The study of toxic and carcinogenic substances in foods represents one of the most demanding areas in food safety, due to their repercussions for public health. One potentially toxic compound for humans is ethyl carbamate (EC). EC is a multi-site genotoxic carcinogen of widespread occurrence in fermented foods and alcoholic beverages. Structural and thermal stability of charge-transfer complexes formed between EC as a donor with quinol (QL), picric acid (PA), chloranilic acid (CLA), p-chloranil (p-CHL) and 1,3-dinitrobenzene (DNB) as acceptors were reported. Elemental analysis (CHN), electronic absorption spectra, photometric titration, IR, and 1H NMR spectra show that the interaction between EC and acceptors was stabilized by hydrogen bonding, via a 1:1 stoichiometry. Thermogravimetric (TG) analysis indicates that the formation of molecular CT complexes was stable, exothermic and spontaneous. Finally, the CT complexes were screened for their antibacterial and antifungal activities. The results indicated that the [(EC)(QL)] complex exhibited strong antimicrobial activities against various bacterial and fungal strains compared with standard drugs.

  20. Bayesian parameter estimation for the Wnt pathway: an infinite mixture models approach.

    PubMed

    Koutroumpas, Konstantinos; Ballarini, Paolo; Votsi, Irene; Cournède, Paul-Henry

    2016-09-01

    Likelihood-free methods, like Approximate Bayesian Computation (ABC), have been extensively used in model-based statistical inference with intractable likelihood functions. When combined with Sequential Monte Carlo (SMC) algorithms they constitute a powerful approach for parameter estimation and model selection of mathematical models of complex biological systems. A crucial step in the ABC-SMC algorithms, significantly affecting their performance, is the propagation of a set of parameter vectors through a sequence of intermediate distributions using Markov kernels. In this article, we employ Dirichlet process mixtures (DPMs) to design optimal transition kernels and we present an ABC-SMC algorithm with DPM kernels. We illustrate the use of the proposed methodology using real data for the canonical Wnt signaling pathway. A multi-compartment model of the pathway is developed and it is compared to an existing model. The results indicate that DPMs are more efficient in the exploration of the parameter space and can significantly improve ABC-SMC performance. In comparison to alternative sampling schemes that are commonly used, the proposed approach can bring potential benefits in the estimation of complex multimodal distributions. The method is used to estimate the parameters and the initial state of two models of the Wnt pathway and it is shown that the multi-compartment model fits better the experimental data. Python scripts for the Dirichlet Process Gaussian Mixture model and the Gibbs sampler are available at https://sites.google.com/site/kkoutroumpas/software konstantinos.koutroumpas@ecp.fr. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Mechanism of cinnamic acid-induced trypsin inhibition: A multi-technique approach

    NASA Astrophysics Data System (ADS)

    Zhang, Hongmei; Zhou, Qiuhua; Cao, Jian; Wang, Yanqing

    2013-12-01

    In order to investigate the association of the protease trypsin with cinnamic acid, the interaction was characterized by using fluorescence, UV-vis absorption spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding process may be outlined as follows: cinnamic acid can interact with trypsin with one binding site to form cinnamic acid-trypsin complex, resulting in inhibition of trypsin activity; the spectroscopic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being -8.95 kJ mol-1 and 50.70 J mol-1 K-1, respectively. Noncovalent interactions make the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic acid can enter into the primary substrate-binding pocket and alter the environment around Trp and Tyr residues.

  2. Biomarker responses to environmental contamination in estuaries: A comparative multi-taxa approach.

    PubMed

    Duarte, Irina A; Reis-Santos, Patrick; França, Susana; Cabral, Henrique; Fonseca, Vanessa F

    2017-08-01

    Estuaries are highly productive ecosystems subjected to numerous anthropogenic pressures with consequent environmental quality degradation. In this study, multiple biomarker responses [superoxide dismutase (SOD), catalase (CAT), ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities, as well as lipid peroxidation (LPO) and DNA damage (DNAd)] were determined in two fish (Dicentrarchus labrax and Pomatoschistus microps) and four macroinvertebrate species (Carcinus maenas, Crangon crangon, Hediste diversicolor and Scrobicularia plana) from the Ria de Aveiro and Tejo estuaries over distinct months. Two sites per estuarine system were selected based on anthropogenic pressures and magnitude of environmental contamination. Antioxidant enzyme activities in fish species suggested a ubiquitous response to oxidative stress, while biotransformation and effect biomarkers exhibited higher spatial and temporal variation. In invertebrate species, biotransformation enzyme activity was clearly less variable than in fish evidencing lower xenobiotic transformation capability. Overall, largest biomarker responses were found in the most contaminated sites (Tejo), yet species-specific patterns were evident. These should be factored in multi-taxa approaches, considering that the differential functional traits of species, such as habitat use, life-stage, feeding or physiology can influence exposure routes and biomarker responses. The Integrated Biomarker Response index highlighted patterns in biomarker responses which were not immediately evident when analyzing biomarkers individually. Overall, results provided insights into the complexity of species responses to contamination in naturally varying estuarine environments. Ultimately, multi-taxa and multi-biomarker approaches provide a comprehensive and complementary view of ecosystem health, encompassing diverse forms of biological integration and exposure routes, and allow the validation of results among markers and species. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 75 FR 26793 - Arcelor Mittal Including On-Site Leased Workers From Adecco, ESW, Inc., Guardsmark, Hudson Global...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... On-Site Leased Workers From Adecco, ESW, Inc., Guardsmark, Hudson Global Resources and Multi Serv... and cold rolled steel. The company reports that workers leased from Multi Serv were employed on-site at the Hennepin, Illinois location of Arcelor Mittal. The Department has determined that these...

  4. Robust multi-site MR data processing: iterative optimization of bias correction, tissue classification, and registration.

    PubMed

    Young Kim, Eun; Johnson, Hans J

    2013-01-01

    A robust multi-modal tool, for automated registration, bias correction, and tissue classification, has been implemented for large-scale heterogeneous multi-site longitudinal MR data analysis. This work focused on improving the an iterative optimization framework between bias-correction, registration, and tissue classification inspired from previous work. The primary contributions are robustness improvements from incorporation of following four elements: (1) utilize multi-modal and repeated scans, (2) incorporate high-deformable registration, (3) use extended set of tissue definitions, and (4) use of multi-modal aware intensity-context priors. The benefits of these enhancements were investigated by a series of experiments with both simulated brain data set (BrainWeb) and by applying to highly-heterogeneous data from a 32 site imaging study with quality assessments through the expert visual inspection. The implementation of this tool is tailored for, but not limited to, large-scale data processing with great data variation with a flexible interface. In this paper, we describe enhancements to a joint registration, bias correction, and the tissue classification, that improve the generalizability and robustness for processing multi-modal longitudinal MR scans collected at multi-sites. The tool was evaluated by using both simulated and simulated and human subject MRI images. With these enhancements, the results showed improved robustness for large-scale heterogeneous MRI processing.

  5. The UNAVCO role in planning, building, and maintaining geodetic infrastructure across the Americas: update on PBO, COCONet, and TLALOCNet

    NASA Astrophysics Data System (ADS)

    Mattioli, G. S.; Braun, J. J.; Cabral, E.; Calais, E.; DeMets, C.; Feaux, K.; Mencin, D.; Miller, M. M.; Normandeau, J.; Serra, Y.; Wang, G.

    2013-05-01

    UNAVCO maintains the NSF-funded Plate Boundary Observatory (PBO), which is the geodetic facility of EarthScope. PBO is largest continuous GPS and borehole geophysical network in the Americas, with ~1130 cGPS sites, including several with multiple monuments, ~80 boreholes, with 75 tensor strainmeters, 79 short-period, 3-component seismometers, and pore pressure sensors at 23 sites. PBO also includes 26 tiltmeters deployed at several volcanoes. Surface meteorological sensors are collocated at 134 GPS sites. UNAVCO provides high-rate (1 Hz), low-latency (<1 s) GPS data streams (RT-GPS) from 348 stations in PBO and has delivered over 62 Tb of geodetic data since PBO's inception in 2004. COCONet is a multi-hazard GPS-Met observatory, which extends PBO infrastructure into the Caribbean basin. In 2010, UNAVCO in collaboration with UCAR, was funded by NSF to build and initially maintain a network of 50 new cGPS/Met sites and incorporate another 50 existing sites in the Caribbean region. The revised siting plan calls for 46 new, 21 refurbished, and 77 existing stations spanning 26 nations in the Caribbean. Data from COCONet sites flow into the UNAVCO archive and are processed by the PBO analysis centers. Three workshops have helped to foster a COCONet science community and provide important guidance to UNAVCO to assure success of this complex multi-national project. A new joint UNAVCO-Mexican multi-hazard GPS-Met observatory, called TLALOCNet, has been proposed based on the outcomes of a NSF-funded workshop held in Puerto Vallarta in 2010. The TLALOCNet plan calls for UNAVCO to install 9 new PBO-quality GPS-Met sites in Mexico and adjacent islands, upgrade 29 sites previously installed with NSF funding along the western subduction boundary, and coordinate with the Mexican National Meteorological Service to federate data from at least another 80 GPS-Met sites distributed across Mexico. All GPS-Met data from TLALOCNet will be freely available at the UNAVCO archive and Mexican mirror sites. The ultimate goal for these networks is to provide free, high-quality, low-latency data and data products for researchers, educators, students, and the private sector. Data from COCONet and TLALOCNet will be used by US and international scientists to study solid earth processes, for example plate kinematics and dynamic as well as plate boundary interactions and deformation, with an emphasis on the earthquake cycle. The networks also serve atmospheric science objectives by providing more precise estimates of tropospheric water vapor thus enabling better forecast of the dynamics of airborne moisture associated with the yearly Caribbean hurricane cycle.

  6. River rating complexity

    USGS Publications Warehouse

    Holmes, Robert R.

    2016-01-01

    Accuracy of streamflow data depends on the veracity of the rating model used to derive a continuous time series of discharge from the surrogate variables that can readily be collected autonomously at a streamgage. Ratings are typically represented as a simple monotonic increasing function (simple rating), meaning the discharge is a function of stage alone, however this is never truly the case unless the flow is completely uniform at all stages and in transitions from one stage to the next. For example, at some streamflow-monitoring sites the discharge on the rising limb of the hydrograph is discernably larger than the discharge at the same stage on the falling limb of the hydrograph. This is the so-called “loop rating curve” (loop rating). In many cases, these loops are quite small and variation between rising- and falling-limb discharge measurements made at the same stage are well within the accuracy of the measurements. However, certain hydraulic conditions can produce a loop that is large enough to preclude use of a monotonic rating. A detailed data campaign for the Mississippi River at St. Louis, Missouri during a multi-peaked flood over a 56-day period in 2015 demonstrates the rating complexity at this location. The shifting-control method used to deal with complexity at this site matched all measurements within 8%.

  7. Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2.

    PubMed

    Lo, Te-Wen; Bennett, Daniel C; Goodman, S Jay; Stern, Michael J

    2010-06-01

    The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy-terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi-substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly.

  8. Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance.

    PubMed

    Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

    2016-02-27

    MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables.

  9. Exploring Transformations in Caribbean Indigenous Social Networks through Visibility Studies: the Case of Late Pre-Colonial Landscapes in East-Guadeloupe (French West Indies).

    PubMed

    Brughmans, Tom; de Waal, Maaike S; Hofman, Corinne L; Brandes, Ulrik

    2018-01-01

    This paper presents a study of the visual properties of natural and Amerindian cultural landscapes in late pre-colonial East-Guadeloupe and of how these visual properties affected social interactions. Through a review of descriptive and formal visibility studies in Caribbean archaeology, it reveals that the ability of visual properties to affect past human behaviour is frequently evoked but the more complex of these hypotheses are rarely studied formally. To explore such complex hypotheses, the current study applies a range of techniques: total viewsheds, cumulative viewsheds, visual neighbourhood configurations and visibility networks. Experiments were performed to explore the control of seascapes, the functioning of hypothetical smoke signalling networks, the correlation of these visual properties with stylistic similarities of material culture found at sites and the change of visual properties over time. The results of these experiments suggest that only few sites in Eastern Guadeloupe are located in areas that are particularly suitable to visually control possible sea routes for short- and long-distance exchange; that visual control over sea areas was not a factor of importance for the existence of micro-style areas; that during the early phase of the Late Ceramic Age networks per landmass are connected and dense and that they incorporate all sites, a structure that would allow hypothetical smoke signalling networks; and that the visual properties of locations of the late sites Morne Souffleur and Morne Cybèle-1 were not ideal for defensive purposes. These results led us to propose a multi-scalar hypothesis for how lines of sight between settlements in the Lesser Antilles could have structured past human behaviour: short-distance visibility networks represent the structuring of navigation and communication within landmasses, whereas the landmasses themselves served as focal points for regional navigation and interaction. We conclude by emphasising that since our archaeological theories about visual properties usually take a multi-scalar landscape perspective, there is a need for this perspective to be reflected in our formal visibility methods as is made possible by the methods used in this paper.

  10. Tools and Methods for Risk Management in Multi-Site Engineering Projects

    NASA Astrophysics Data System (ADS)

    Zhou, Mingwei; Nemes, Laszlo; Reidsema, Carl; Ahmed, Ammar; Kayis, Berman

    In today's highly global business environment, engineering and manufacturing projects often involve two or more geographically dispersed units or departments, research centers or companies. This paper attempts to identify the requirements for risk management in a multi-site engineering project environment, and presents a review of the state-of-the-art tools and methods that can be used to manage risks in multi-site engineering projects. This leads to the development of a risk management roadmap, which will underpin the design and implementation of an intelligent risk mapping system.

  11. Research on Geo-information Data Model for Preselected Areas of Geological Disposal of High-level Radioactive Waste

    NASA Astrophysics Data System (ADS)

    Gao, M.; Huang, S. T.; Wang, P.; Zhao, Y. A.; Wang, H. B.

    2016-11-01

    The geological disposal of high-level radioactive waste (hereinafter referred to "geological disposal") is a long-term, complex, and systematic scientific project, whose data and information resources in the research and development ((hereinafter referred to ”R&D”) process provide the significant support for R&D of geological disposal system, and lay a foundation for the long-term stability and safety assessment of repository site. However, the data related to the research and engineering in the sitting of the geological disposal repositories is more complicated (including multi-source, multi-dimension and changeable), the requirements for the data accuracy and comprehensive application has become much higher than before, which lead to the fact that the data model design of geo-information database for the disposal repository are facing more serious challenges. In the essay, data resources of the pre-selected areas of the repository has been comprehensive controlled and systematic analyzed. According to deeply understanding of the application requirements, the research work has made a solution for the key technical problems including reasonable classification system of multi-source data entity, complex logic relations and effective physical storage structures. The new solution has broken through data classification and conventional spatial data the organization model applied in the traditional industry, realized the data organization and integration with the unit of data entities and spatial relationship, which were independent, holonomic and with application significant features in HLW geological disposal. The reasonable, feasible and flexible data conceptual models, logical models and physical models have been established so as to ensure the effective integration and facilitate application development of multi-source data in pre-selected areas for geological disposal.

  12. Beam-dynamics driven design of the LHeC energy-recovery linac

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

    Pellegrini, Dario; Latina, Andrea; Schulte, Daniel

    The LHeC study is a possible upgrade of the LHC that aims at delivering an electron beam for collisions with the existing hadronic beams. The current baseline design for the electron facility consists of a multi-pass superconducting energy-recovery linac operating in a continuous wave mode. Here, we summarize the overall layout of such ERL complex located on the LHC site and introduce the most recent developments. We review of the lattice components, presenting their baseline design along with possible alternatives that aims at improving the overall machine performance. The detector bypass has been designed and integrated into the lattice. Trackingmore » simulations allowed us to verify the high current (~150 mA in the linacs) beam operation required for the LHeC to serve as an Higgs Factory. The impact of single and multi-bunch wake-fields, synchrotron radiation and beam-beam effects has been assessed in this paper.« less

  13. Beam-dynamics driven design of the LHeC energy-recovery linac

    DOE PAGES

    Pellegrini, Dario; Latina, Andrea; Schulte, Daniel; ...

    2015-12-23

    The LHeC study is a possible upgrade of the LHC that aims at delivering an electron beam for collisions with the existing hadronic beams. The current baseline design for the electron facility consists of a multi-pass superconducting energy-recovery linac operating in a continuous wave mode. Here, we summarize the overall layout of such ERL complex located on the LHC site and introduce the most recent developments. We review of the lattice components, presenting their baseline design along with possible alternatives that aims at improving the overall machine performance. The detector bypass has been designed and integrated into the lattice. Trackingmore » simulations allowed us to verify the high current (~150 mA in the linacs) beam operation required for the LHeC to serve as an Higgs Factory. The impact of single and multi-bunch wake-fields, synchrotron radiation and beam-beam effects has been assessed in this paper.« less

  14. #Learning: The use of back channel technology in multi-campus nursing education.

    PubMed

    Yates, Karen; Birks, Melanie; Woods, Cindy; Hitchins, Marnie

    2015-09-01

    This paper reports on the results of a study into the use of microblogging technology (TodaysMeet) in large, multi-site lectures in a nursing program. The aim of this study was to investigate students' use of the technology and their perceptions of its value in stimulating engagement in a complex learning environment. The study demonstrated that students like the anonymity that the technology provided, allowing them to ask questions without fear of appearing less competent than their peers. Many of the respondents commented positively on the opportunity to engage with students and the lecturer at other campuses. While some students appreciated the opportunity to interact and have feedback from peers, others saw this as a negative aspect of the technology. This study suggests that, used appropriately, microblogging can be incorporated into large lectures to promote student participation and engagement and ultimately enhance the learning process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Reduced complexity of multi-track joint 2-D Viterbi detectors for bit-patterned media recording channel

    NASA Astrophysics Data System (ADS)

    Myint, L. M. M.; Warisarn, C.

    2017-05-01

    Two-dimensional (2-D) interference is one of the prominent challenges in ultra-high density recording system such as bit patterned media recording (BPMR). The multi-track joint 2-D detection technique with the help of the array-head reading can tackle this problem effectively by jointly processing the multiple readback signals from the adjacent tracks. Moreover, it can robustly alleviate the impairments due to track mis-registration (TMR) and media noise. However, the computational complexity of such detectors is normally too high and hard to implement in a reality, even for a few multiple tracks. Therefore, in this paper, we mainly focus on reducing the complexity of multi-track joint 2-D Viterbi detector without paying a large penalty in terms of the performance. We propose a simplified multi-track joint 2-D Viterbi detector with a manageable complexity level for the BPMR's multi-track multi-head (MTMH) system. In the proposed method, the complexity of detector's trellis is reduced with the help of the joint-track equalization method which employs 1-D equalizers and 2-D generalized partial response (GPR) target. Moreover, we also examine the performance of a full-fledged multi-track joint 2-D detector and the conventional 2-D detection. The results show that the simplified detector can perform close to the full-fledge detector, especially when the system faces high media noise, with the significant low complexity.

  16. Negotiating designs of multi-purpose reservoir systems in international basins

    NASA Astrophysics Data System (ADS)

    Geressu, Robel; Harou, Julien

    2016-04-01

    Given increasing agricultural and energy demands, coordinated management of multi-reservoir systems could help increase production without further stressing available water resources. However, regional or international disputes about water-use rights pose a challenge to efficient expansion and management of many large reservoir systems. Even when projects are likely to benefit all stakeholders, agreeing on the design, operation, financing, and benefit sharing can be challenging. This is due to the difficulty of considering multiple stakeholder interests in the design of projects and understanding the benefit trade-offs that designs imply. Incommensurate performance metrics, incomplete knowledge on system requirements, lack of objectivity in managing conflict and difficulty to communicate complex issue exacerbate the problem. This work proposes a multi-step hybrid multi-objective optimization and multi-criteria ranking approach for supporting negotiation in water resource systems. The approach uses many-objective optimization to generate alternative efficient designs and reveal the trade-offs between conflicting objectives. This enables informed elicitation of criteria weights for further multi-criteria ranking of alternatives. An ideal design would be ranked as best by all stakeholders. Resource-sharing mechanisms such as power-trade and/or cost sharing may help competing stakeholders arrive at designs acceptable to all. Many-objective optimization helps suggests efficient designs (reservoir site, its storage size and operating rule) and coordination levels considering the perspectives of multiple stakeholders simultaneously. We apply the proposed approach to a proof-of-concept study of the expansion of the Blue Nile transboundary reservoir system.

  17. Exploiting Multisite Gateway and pENFRUIT plasmid collection for fruit genetic engineering.

    PubMed

    Estornell, Leandro H; Granell, Antonio; Orzaez, Diego

    2012-01-01

    MultiSite Gateway cloning techniques based on homologous recombination facilitate the combinatorial assembly of basic genetic pieces (i.e., promoters, CDS, and terminators) into gene expression or gene silencing cassettes. pENFRUIT is a collection of MultiSite Triple Gateway Entry vectors dedicated to genetic engineering in fruits. It comprises a number of fruit-operating promoters as well as C-terminal tags adapted to the Gateway standard. In this way, flanking regulatory/labeling sequences can be easily Gateway-assembled with a given gene of interest for its ectopic expression or silencing in fruits. The resulting gene constructs can be analyzed in stable transgenic plants or in transient expression assays, the latter allowing fast testing of the increasing number of combinations arising from MultiSite methodology. A detailed description of the use of MultiSite cloning methodology for the assembly of pENFRUIT elements is presented.

  18. 75 FR 30065 - Arcelor Mittal, Including On-Site Leased Workers From Adecco, ESW, Inc., Guardsmark, Hudson...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-28

    ... On-Site Leased Workers From Adecco, ESW, Inc., Guardsmark, Hudson Global Resources, Multi Serv and... leased workers from Multi Serv. The notice was published in the Federal Register on May 12, 2010 (75 FR... reports that workers leased from Quaker Chemical were employed on-site at the Hennepin, Illinois location...

  19. Multi-disciplinary team meetings in stroke rehabilitation: an observation study and conceptual framework.

    PubMed

    Tyson, S F; Burton, L; McGovern, A

    2014-12-01

    To explore how multi-disciplinary team meetings operate in stroke rehabilitation. Non-participant observation of multi-disciplinary team meetings and semi-structured interviews with attending staff. Twelve meetings were observed (at least one at each site) and 18 staff (one psychologist, one social worker; four nurses; four physiotherapists four occupational therapists, two speech and language therapists, one stroke co-ordinator and one stroke ward manager) were interviewed in eight in-patient stroke rehabilitation units. Multi-disciplinary team meetings in stroke rehabilitation were complex, demanding and highly varied. A model emerged which identified the main inputs to influence conduct of the meetings were personal contributions of the members and structure and format of the meetings. These were mediated by the team climate and leadership skills of the chair. The desired outputs; clinical decisions and the attributes of apparently effective meetings were identified by the staff. A notable difference between the meetings that staff considered effective and those that were not, was their structure and format. Successful meetings tended to feature a set agenda, structured documentation; formal use of measurement tools; pre-meeting preparation and skilled chairing. These features were often absent in meetings perceived to be ineffective. The main features of operation of multi-disciplinary team meetings have been identified which will enable assessment tools and interventions to improve effectiveness to be developed. © The Author(s) 2014.

  20. Managing personal health information in distributed research network environments.

    PubMed

    Bredfeldt, Christine E; Butani, Amy L; Pardee, Roy; Hitz, Paul; Padmanabhan, Sandy; Saylor, Gwyn

    2013-10-08

    Studying rare outcomes, new interventions and diverse populations often requires collaborations across multiple health research partners. However, transferring healthcare research data from one institution to another can increase the risk of data privacy and security breaches. A working group of multi-site research programmers evaluated the need for tools to support data security and data privacy. The group determined that data privacy support tools should: 1) allow for a range of allowable Protected Health Information (PHI); 2) clearly identify what type of data should be protected under the Health Insurance Portability and Accountability Act (HIPAA); and 3) help analysts identify which protected health information data elements are allowable in a given project and how they should be protected during data transfer. Based on these requirements we developed two performance support tools to support data programmers and site analysts in exchanging research data. The first tool, a workplan template, guides the lead programmer through effectively communicating the details of multi-site programming, including how to run the program, what output the program will create, and whether the output is expected to contain protected health information. The second performance support tool is a checklist that site analysts can use to ensure that multi-site program output conforms to expectations and does not contain protected health information beyond what is allowed under the multi-site research agreements. Together the two tools create a formal multi-site programming workflow designed to reduce the chance of accidental PHI disclosure.

  1. Phytoextraction of heavy metals by potential native plants and their microscopic observation of root growing on stabilised distillery sludge as a prospective tool for in situ phytoremediation of industrial waste.

    PubMed

    Chandra, Ram; Kumar, Vineet

    2017-01-01

    The safe disposal of post-methanated distillery sludge (PMDS) in the environment is challenging due to high concentrations of heavy metals along with other complex organic pollutants. The study has revealed that PMDS contained high amounts of Fe (2403), Zn (210), Mn (126), Cu (73.62), Cr (21.825), Pb (16.33) and Ni (13.425 mg kg -1 ) along with melanoidins and other co-pollutants. The phytoextraction pattern in 15 potential native plants growing on sludge showed that the Blumea lacera, Parthenium hysterophorous, Setaria viridis, Chenopodium album, Cannabis sativa, Basella alba, Tricosanthes dioica, Amaranthus spinosus L., Achyranthes sp., Dhatura stramonium, Sacchrum munja and Croton bonplandianum were noted as root accumulator for Fe, Zn and Mn, while S. munja, P. hysterophorous, C. sativa, C. album, T. dioica, D. stramonium, B. lacera, B. alba, Kalanchoe pinnata and Achyranthes sp. were found as shoot accumulator for Fe. In addition, A. spinosus L. was found as shoot accumulator for Zn and Mn. Similarly, all plants found as leaf accumulator for Fe, Zn and Mn except A. spinosus L. and Ricinus communis. Further, the BCF of all tested plants were noted <1, while the TF showed >1. This revealed that metal bioavailability to plant is poor due to strong complexation of heavy metals with organic pollutants. This gives a strong evidence of hyperaccumulation for the tested metals from complex distillery waste. Furthermore, the TEM observations of root of P. hysterophorous, C. sativa, Solanum nigrum and R. communis showed formation of multi-nucleolus, multi-vacuoles and deposition of metal granules in cellular component of roots as a plant adaptation mechanism for phytoextraction of heavy metal-rich polluted site. Hence, these native plants may be used as a tool for in situ phytoremediation and eco-restoration of industrial waste-contaminated site.

  2. Multi-Destination and Multi-Purpose Trip Effects in the Analysis of the Demand for Trips to a Remote Recreational Site

    NASA Astrophysics Data System (ADS)

    Martínez-Espiñeira, Roberto; Amoako-Tuffour, Joe

    2009-06-01

    One of the basic assumptions of the travel cost method for recreational demand analysis is that the travel cost is always incurred for a single purpose recreational trip. Several studies have skirted around the issue with simplifying assumptions and dropping observations considered as nonconventional holiday-makers or as nontraditional visitors from the sample. The effect of such simplifications on the benefit estimates remains conjectural. Given the remoteness of notable recreational parks, multi-destination or multi-purpose trips are not uncommon. This article examines the consequences of allocating travel costs to a recreational site when some trips were taken for purposes other than recreation and/or included visits to other recreational sites. Using a multi-purpose weighting approach on data from Gros Morne National Park, Canada, we conclude that a proper correction for multi-destination or multi-purpose trip is more of what is needed to avoid potential biases in the estimated effects of the price (travel-cost) variable and of the income variable in the trip generation equation.

  3. Study of a metallurgical site in Tuscany (Italy) by radiocarbon dating

    NASA Astrophysics Data System (ADS)

    Cartocci, A.; Fedi, M. E.; Taccetti, F.; Benvenuti, M.; Chiarantini, L.; Guideri, S.

    2007-06-01

    Tuscany represents one of the most important ancient mining districts of Italy. Metalworking activities have been present in the area since ancient times and several mining centres have been active in the region since the Etruscan period. Two of the more notable mining locations are the island of Elba and the towns of Populonia and Massa Marittima. In order to reconstruct the development of metallurgical techniques in the past, a multi-disciplinary approach is required, involving both archaeological study and archaeometric analysis of the sites of interest. One of the most complex problems is establishing the chronological history of metallurgical exploitation in ancient sites: archaeological remains are sometimes incomplete and the stratigraphy of archaeological horizons might have been deeply altered. Thus, direct dating of metallurgical slags and other remains of mining and metalworking activities using radiocarbon measurements is particularly useful for developing site chronologies. Charcoal samples from a recent excavation in Populonia were dated by AMS radiocarbon in order to reconstruct the chronological evolution of ancient metallurgical production; results reported here are consistent with archaeological observations.

  4. Understanding Prairie Fen Hydrology - a Hierarchical Multi-Scale Groundwater Modeling Approach

    NASA Astrophysics Data System (ADS)

    Sampath, P.; Liao, H.; Abbas, H.; Ma, L.; Li, S.

    2012-12-01

    Prairie fens provide critical habitat to more than 50 rare species and significantly contribute to the biodiversity of the upper Great Lakes region. The sustainability of these globally unique ecosystems, however, requires that they be fed by a steady supply of pristine, calcareous groundwater. Understanding the hydrology that supports the existence of such fens is essential in preserving these valuable habitats. This research uses process-based multi-scale groundwater modeling for this purpose. Two fen-sites, MacCready Fen and Ives Road Fen, in Southern Michigan were systematically studied. A hierarchy of nested steady-state models was built for each fen-site to capture the system's dynamics at spatial scales ranging from the regional groundwater-shed to the local fens. The models utilize high-resolution Digital Elevation Models (DEM), National Hydrologic Datasets (NHD), a recently-assembled water-well database, and results from a state-wide groundwater mapping project to represent the complex hydro-geological and stress framework. The modeling system simulates both shallow glacial and deep bedrock aquifers as well as the interaction between surface water and groundwater. Aquifer heterogeneities were explicitly simulated with multi-scale transition probability geo-statistics. A two-way hydraulic head feedback mechanism was set up between the nested models, such that the parent models provided boundary conditions to the child models, and in turn the child models provided local information to the parent models. A hierarchical mass budget analysis was performed to estimate the seepage fluxes at the surface water/groundwater interfaces and to assess the relative importance of the processes at multiple scales that contribute water to the fens. The models were calibrated using observed base-flows at stream gauging stations and/or static water levels at wells. Three-dimensional particle tracking was used to predict the sources of water to the fens. We observed from the multi-scale simulations that the water system that supports the fens is a much larger, more connected, and more complex one than expected. The water in the fen can be traced back to a network of sources, including lakes and wetlands at different elevations, which are connected to a regional mound through a "cascade delivery mechanism". This "master recharge area" is the ultimate source of water not only to the fens in its vicinity, but also for many major rivers and aquifers. The implication of this finding is that prairie fens must be managed as part of a much larger, multi-scale groundwater system and we must consider protection of the shorter and long-term water sources. This will require a fundamental reassessment of our current approach to fen conservation, which is primarily based on protection of individual fens and their immediate surroundings. Clearly, in the future we must plan for conservation of the broad recharge areas and the multiple fen complexes they support.

  5. Modeling synthetic lethality

    PubMed Central

    Le Meur, Nolwenn; Gentleman, Robert

    2008-01-01

    Background Synthetic lethality defines a genetic interaction where the combination of mutations in two or more genes leads to cell death. The implications of synthetic lethal screens have been discussed in the context of drug development as synthetic lethal pairs could be used to selectively kill cancer cells, but leave normal cells relatively unharmed. A challenge is to assess genome-wide experimental data and integrate the results to better understand the underlying biological processes. We propose statistical and computational tools that can be used to find relationships between synthetic lethality and cellular organizational units. Results In Saccharomyces cerevisiae, we identified multi-protein complexes and pairs of multi-protein complexes that share an unusually high number of synthetic genetic interactions. As previously predicted, we found that synthetic lethality can arise from subunits of an essential multi-protein complex or between pairs of multi-protein complexes. Finally, using multi-protein complexes allowed us to take into account the pleiotropic nature of the gene products. Conclusions Modeling synthetic lethality using current estimates of the yeast interactome is an efficient approach to disentangle some of the complex molecular interactions that drive a cell. Our model in conjunction with applied statistical methods and computational methods provides new tools to better characterize synthetic genetic interactions. PMID:18789146

  6. Spatial distribution and source identification of indicator polychlorinated biphenyls in soil collected from the coastal multi-industrial city of Ulsan, South Korea for three consecutive years.

    PubMed

    Nguyen, Tuyet Nam Thi; Kwon, Hye-Ok; Lee, Yun-Se; Kim, Leesun; Lee, Sung-Eun; Choi, Sung-Deuk

    2016-11-01

    The concentrations, profiles, and source-receptor relationships of seven indicator polychlorinated biphenyls (PCBs) (#28, 52, 101, 118, 138, 153, and 180) found in soil at 25 rural, urban, and industrial sites in Ulsan, South Korea were investigated. For this study, 75 soil samples were collected, 25 each in January of 2011, 2012, and 2013. Principal component analysis was used to evaluate the influence of the emission sources on the soil samples. The concentrations of total seven PCBs (Σ7 PCBs) ranged between 0.034 ng/g and 143 ng/g (mean: 5.10 ng/g, median: 0.440 ng/g), which indicated slight or moderate contamination levels, respectively, compared to those in the other countries or other cities in Korea. The concentrations of Σ7 PCBs at the industrial and urban sites were significantly higher than those at the rural sites, due to the direct influence of emission sources related to industrial activities rather than urban emission sources. Generally, the profiles of PCBs were dominated by penta- and hexa-chlorinated biphenyls at all the study sites, suggesting common sources of PCBs in Ulsan. PCB source identification indicated that leakage from transformer oils in the major industrial complexes and PCB-containing paints used in the automobile and shipbuilding industrial complexes were possibly the main sources of indicator PCBs in the study areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Evaluating the performance of land surface model ORCHIDEE-CAN v1.0 on water and energy flux estimation with a single- and multi-layer energy budget scheme

    NASA Astrophysics Data System (ADS)

    Chen, Yiying; Ryder, James; Bastrikov, Vladislav; McGrath, Matthew J.; Naudts, Kim; Otto, Juliane; Ottlé, Catherine; Peylin, Philippe; Polcher, Jan; Valade, Aude; Black, Andrew; Elbers, Jan A.; Moors, Eddy; Foken, Thomas; van Gorsel, Eva; Haverd, Vanessa; Heinesch, Bernard; Tiedemann, Frank; Knohl, Alexander; Launiainen, Samuli; Loustau, Denis; Ogée, Jérôme; Vessala, Timo; Luyssaert, Sebastiaan

    2016-09-01

    Canopy structure is one of the most important vegetation characteristics for land-atmosphere interactions, as it determines the energy and scalar exchanges between the land surface and the overlying air mass. In this study we evaluated the performance of a newly developed multi-layer energy budget in the ORCHIDEE-CAN v1.0 land surface model (Organising Carbon and Hydrology In Dynamic Ecosystems - CANopy), which simulates canopy structure and can be coupled to an atmospheric model using an implicit coupling procedure. We aim to provide a set of acceptable parameter values for a range of forest types. Top-canopy and sub-canopy flux observations from eight sites were collected in order to conduct this evaluation. The sites crossed climate zones from temperate to boreal and the vegetation types included deciduous, evergreen broad-leaved and evergreen needle-leaved forest with a maximum leaf area index (LAI; all-sided) ranging from 3.5 to 7.0. The parametrization approach proposed in this study was based on three selected physical processes - namely the diffusion, advection, and turbulent mixing within the canopy. Short-term sub-canopy observations and long-term surface fluxes were used to calibrate the parameters in the sub-canopy radiation, turbulence, and resistance modules with an automatic tuning process. The multi-layer model was found to capture the dynamics of sub-canopy turbulence, temperature, and energy fluxes. The performance of the new multi-layer model was further compared against the existing single-layer model. Although the multi-layer model simulation results showed few or no improvements to both the nighttime energy balance and energy partitioning during winter compared with a single-layer model simulation, the increased model complexity does provide a more detailed description of the canopy micrometeorology of various forest types. The multi-layer model links to potential future environmental and ecological studies such as the assessment of in-canopy species vulnerability to climate change, the climate effects of disturbance intensities and frequencies, and the consequences of biogenic volatile organic compound (BVOC) emissions from the terrestrial ecosystem.

  8. The 2-oxoacid dehydrogenase multi-enzyme complex of the archaeon Thermoplasma acidophilum - recombinant expression, assembly and characterization.

    PubMed

    Heath, Caroline; Posner, Mareike G; Aass, Hans C; Upadhyay, Abhishek; Scott, David J; Hough, David W; Danson, Michael J

    2007-10-01

    The aerobic archaea possess four closely spaced, adjacent genes that encode proteins showing significant sequence identities with the bacterial and eukaryal components comprising the 2-oxoacid dehydrogenase multi-enzyme complexes. However, catalytic activities of such complexes have never been detected in the archaea, although 2-oxoacid ferredoxin oxidoreductases that catalyze the equivalent metabolic reactions are present. In the current paper, we clone and express the four genes from the thermophilic archaeon, Thermoplasma acidophilum, and demonstrate that the recombinant enzymes are active and assemble into a large (M(r) = 5 x 10(6)) multi-enzyme complex. The post-translational incorporation of lipoic acid into the transacylase component of the complex is demonstrated, as is the assembly of this enzyme into a 24-mer core to which the other components bind to give the functional multi-enzyme system. This assembled complex is shown to catalyze the oxidative decarboxylation of branched-chain 2-oxoacids and pyruvate to their corresponding acyl-CoA derivatives. Our data constitute the first proof that the archaea possess a functional 2-oxoacid dehydrogenase complex.

  9. Analysis Concerning the Inspection Threshold for Multi-Site Damage.

    DOT National Transportation Integrated Search

    1993-12-01

    Periodic inspections, at a prescribed interval, for Multi-Site Damage (MS) in longitudinal fuselage lap-joints start when the aircraft has accumulated a certain number of flights, the inspection threshold. The work reported here was an attempt to obt...

  10. Hazard and operability study of the multi-function Waste Tank Facility. Revision 1

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

    Hughes, M.E.

    1995-05-15

    The Multi-Function Waste Tank Facility (MWTF) East site will be constructed on the west side of the 200E area and the MWTF West site will be constructed in the SW quadrant of the 200W site in the Hanford Area. This is a description of facility hazards that site personnel or the general public could potentially be exposed to during operation. A list of preliminary Design Basis Accidents was developed.

  11. Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance

    PubMed Central

    Helmer, K. G.; Chou, M-C.; Preciado, R. I.; Gimi, B.; Rollins, N. K.; Song, A.; Turner, J.; Mori, S.

    2016-01-01

    MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables. PMID:27350723

  12. Neuroanatomical morphometric characterization of sex differences in youth using statistical learning.

    PubMed

    Sepehrband, Farshid; Lynch, Kirsten M; Cabeen, Ryan P; Gonzalez-Zacarias, Clio; Zhao, Lu; D'Arcy, Mike; Kesselman, Carl; Herting, Megan M; Dinov, Ivo D; Toga, Arthur W; Clark, Kristi A

    2018-05-15

    Exploring neuroanatomical sex differences using a multivariate statistical learning approach can yield insights that cannot be derived with univariate analysis. While gross differences in total brain volume are well-established, uncovering the more subtle, regional sex-related differences in neuroanatomy requires a multivariate approach that can accurately model spatial complexity as well as the interactions between neuroanatomical features. Here, we developed a multivariate statistical learning model using a support vector machine (SVM) classifier to predict sex from MRI-derived regional neuroanatomical features from a single-site study of 967 healthy youth from the Philadelphia Neurodevelopmental Cohort (PNC). Then, we validated the multivariate model on an independent dataset of 682 healthy youth from the multi-site Pediatric Imaging, Neurocognition and Genetics (PING) cohort study. The trained model exhibited an 83% cross-validated prediction accuracy, and correctly predicted the sex of 77% of the subjects from the independent multi-site dataset. Results showed that cortical thickness of the middle occipital lobes and the angular gyri are major predictors of sex. Results also demonstrated the inferential benefits of going beyond classical regression approaches to capture the interactions among brain features in order to better characterize sex differences in male and female youths. We also identified specific cortical morphological measures and parcellation techniques, such as cortical thickness as derived from the Destrieux atlas, that are better able to discriminate between males and females in comparison to other brain atlases (Desikan-Killiany, Brodmann and subcortical atlases). Copyright © 2018 Elsevier Inc. All rights reserved.

  13. A general Bayesian framework for calibrating and evaluating stochastic models of annual multi-site hydrological data

    NASA Astrophysics Data System (ADS)

    Frost, Andrew J.; Thyer, Mark A.; Srikanthan, R.; Kuczera, George

    2007-07-01

    SummaryMulti-site simulation of hydrological data are required for drought risk assessment of large multi-reservoir water supply systems. In this paper, a general Bayesian framework is presented for the calibration and evaluation of multi-site hydrological data at annual timescales. Models included within this framework are the hidden Markov model (HMM) and the widely used lag-1 autoregressive (AR(1)) model. These models are extended by the inclusion of a Box-Cox transformation and a spatial correlation function in a multi-site setting. Parameter uncertainty is evaluated using Markov chain Monte Carlo techniques. Models are evaluated by their ability to reproduce a range of important extreme statistics and compared using Bayesian model selection techniques which evaluate model probabilities. The case study, using multi-site annual rainfall data situated within catchments which contribute to Sydney's main water supply, provided the following results: Firstly, in terms of model probabilities and diagnostics, the inclusion of the Box-Cox transformation was preferred. Secondly the AR(1) and HMM performed similarly, while some other proposed AR(1)/HMM models with regionally pooled parameters had greater posterior probability than these two models. The practical significance of parameter and model uncertainty was illustrated using a case study involving drought security analysis for urban water supply. It was shown that ignoring parameter uncertainty resulted in a significant overestimate of reservoir yield and an underestimation of system vulnerability to severe drought.

  14. Quantification of source impact to PM using three-dimensional weighted factor model analysis on multi-site data

    NASA Astrophysics Data System (ADS)

    Shi, Guoliang; Peng, Xing; Huangfu, Yanqi; Wang, Wei; Xu, Jiao; Tian, Yingze; Feng, Yinchang; Ivey, Cesunica E.; Russell, Armistead G.

    2017-07-01

    Source apportionment technologies are used to understand the impacts of important sources of particulate matter (PM) air quality, and are widely used for both scientific studies and air quality management. Generally, receptor models apportion speciated PM data from a single sampling site. With the development of large scale monitoring networks, PM speciation are observed at multiple sites in an urban area. For these situations, the models should account for three factors, or dimensions, of the PM, including the chemical species concentrations, sampling periods and sampling site information, suggesting the potential power of a three-dimensional source apportionment approach. However, the principle of three-dimensional Parallel Factor Analysis (Ordinary PARAFAC) model does not always work well in real environmental situations for multi-site receptor datasets. In this work, a new three-way receptor model, called "multi-site three way factor analysis" model is proposed to deal with the multi-site receptor datasets. Synthetic datasets were developed and introduced into the new model to test its performance. Average absolute error (AAE, between estimated and true contributions) for extracted sources were all less than 50%. Additionally, three-dimensional ambient datasets from a Chinese mega-city, Chengdu, were analyzed using this new model to assess the application. Four factors are extracted by the multi-site WFA3 model: secondary source have the highest contributions (64.73 and 56.24 μg/m3), followed by vehicular exhaust (30.13 and 33.60 μg/m3), crustal dust (26.12 and 29.99 μg/m3) and coal combustion (10.73 and 14.83 μg/m3). The model was also compared to PMF, with general agreement, though PMF suggested a lower crustal contribution.

  15. Exponential stability of stochastic complex networks with multi-weights based on graph theory

    NASA Astrophysics Data System (ADS)

    Zhang, Chunmei; Chen, Tianrui

    2018-04-01

    In this paper, a novel approach to exponential stability of stochastic complex networks with multi-weights is investigated by means of the graph-theoretical method. New sufficient conditions are provided to ascertain the moment exponential stability and almost surely exponential stability of stochastic complex networks with multiple weights. It is noted that our stability results are closely related with multi-weights and the intensity of stochastic disturbance. Numerical simulations are also presented to substantiate the theoretical results.

  16. The Search Engine for Multi-Proteoform Complexes: An Online Tool for the Identification and Stoichiometry Determination of Protein Complexes.

    PubMed

    Skinner, Owen S; Schachner, Luis F; Kelleher, Neil L

    2016-12-08

    Recent advances in top-down mass spectrometry using native electrospray now enable the analysis of intact protein complexes with relatively small sample amounts in an untargeted mode. Here, we describe how to characterize both homo- and heteropolymeric complexes with high molecular specificity using input data produced by tandem mass spectrometry of whole protein assemblies. The tool described is a "search engine for multi-proteoform complexes," (SEMPC) and is available for free online. The output is a list of candidate multi-proteoform complexes and scoring metrics, which are used to define a distinct set of one or more unique protein subunits, their overall stoichiometry in the intact complex, and their pre- and post-translational modifications. Thus, we present an approach for the identification and characterization of intact protein complexes from native mass spectrometry data. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  17. Mechanism of cinnamic acid-induced trypsin inhibition: a multi-technique approach.

    PubMed

    Zhang, Hongmei; Zhou, Qiuhua; Cao, Jian; Wang, Yanqing

    2013-12-01

    In order to investigate the association of the protease trypsin with cinnamic acid, the interaction was characterized by using fluorescence, UV-vis absorption spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding process may be outlined as follows: cinnamic acid can interact with trypsin with one binding site to form cinnamic acid-trypsin complex, resulting in inhibition of trypsin activity; the spectroscopic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being -8.95 kJ mol(-1) and 50.70 J mol(-1) K(-1), respectively. Noncovalent interactions make the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic acid can enter into the primary substrate-binding pocket and alter the environment around Trp and Tyr residues. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Multifunctional nanoparticulate polyelectrolyte complexes.

    PubMed

    Hartig, Sean M; Greene, Rachel R; DasGupta, Jayasri; Carlesso, Gianluca; Dikov, Mikhail M; Prokop, Ales; Davidson, Jeffrey M

    2007-12-01

    Water-soluble, biodegradable, polymeric, polyelectrolyte complex dispersions (PECs) have evolved because of the limitations, in terms of toxicity, of the currently available systems. These aqueous nanoparticulate architectures offer a significant advantage for products that may be used as drug delivery systems in humans. PECs are created by mixing oppositely charged polyions. Their hydrodynamic diameter, surface charge, and polydispersity are highly dependent on concentration, ionic strength, pH, and molecular parameters of the polymers that are used. In particular, the complexation between polyelectrolytes with significantly different molecular weights leads to the formation of water-insoluble aggregates. Several PEC characteristics are favorable for cellular uptake and colloidal stability, including hydrodynamic diameter less than 200 nm, surface charge of >30 mV or <-30 mV, spherical morphology, and polydispersity index (PDI) indicative of a homogeneous distribution. Maintenance of these properties is critical for a successful delivery vehicle. This review focuses on the development and potential applications of PECs as multi-functional, site-specific nanoparticulate drug/gene delivery and imaging devices.

  19. Crystal structure of RecBCD enzyme reveals a machine for processing DNA breaks

    NASA Astrophysics Data System (ADS)

    Singleton, Martin R.; Dillingham, Mark S.; Gaudier, Martin; Kowalczykowski, Stephen C.; Wigley, Dale B.

    2004-11-01

    RecBCD is a multi-functional enzyme complex that processes DNA ends resulting from a double-strand break. RecBCD is a bipolar helicase that splits the duplex into its component strands and digests them until encountering a recombinational hotspot (Chi site). The nuclease activity is then attenuated and RecBCD loads RecA onto the 3' tail of the DNA. Here we present the crystal structure of RecBCD bound to a DNA substrate. In this initiation complex, the DNA duplex has been split across the RecC subunit to create a fork with the separated strands each heading towards different helicase motor subunits. The strands pass along tunnels within the complex, both emerging adjacent to the nuclease domain of RecB. Passage of the 3' tail through one of these tunnels provides a mechanism for the recognition of a Chi sequence by RecC within the context of double-stranded DNA. Gating of this tunnel suggests how nuclease activity might be regulated.

  20. Methodological challenges in conducting a multi-site randomized clinical trial of massage therapy in hospice.

    PubMed

    Kutner, Jean; Smith, Marlaine; Mellis, Karen; Felton, Sue; Yamashita, Traci; Corbin, Lisa

    2010-06-01

    Researchers conducting multi-site studies of interventions for end-of-life symptom management face significant challenges with respect to obtaining an adequate sample and training and retaining on-site study teams. The purpose of this paper is to describe the strategies and responses to these challenges in a multi-site randomized clinical trial (RCT) of the efficacy of massage therapy for decreasing pain among patients with advanced cancer in palliative care/hospice settings. Over a period of 36 months, we enrolled 380 participants across 15 sites; 27% of whom withdrew prior to study completion (less than the anticipated 30% rate). We saw an average of 68% turnover amongst study staff. Three key qualities characterized successful on-site study teams: (1) organizational commitment; (2) strong leadership from on-site study coordinators; and (3) effective lines of communication between the on-site study coordinators and both their teams and the university-based research team. Issues of recruitment, retention and training should be accounted for in hospice-based research study design and budgeting.

  1. A general mixture equation of state for double bonding carboxylic acids with ≥2 association sites

    NASA Astrophysics Data System (ADS)

    Marshall, Bennett D.

    2018-05-01

    In this paper, we obtain the first general multi-component solution to Wertheim's thermodynamic perturbation theory for the case that molecules can participate in cyclic double bonds. In contrast to previous authors, we do not restrict double bonding molecules to a 2-site association scheme. Each molecule in a multi-component mixture can have an arbitrary number of donor and acceptor association sites. The one restriction on the theory is that molecules can have at most one pair of double bonding sites. We also incorporate the effect of hydrogen bond cooperativity in cyclic double bonds. We then apply this new association theory to 2-site and 3-site models for carboxylic acids within the polar perturbed chain statistical associating fluid theory equation of state. We demonstrate the accuracy of the approach by comparison to both pure and multi-component phase equilibria data. It is demonstrated that the 3-site association model gives substantially a different hydrogen bonding structure than a 2-site approach. We also demonstrate that inclusion of hydrogen bond cooperativity has a substantial effect on a liquid phase hydrogen bonding structure.

  2. Distortions in Distributions of Impact Estimates in Multi-Site Trials: The Central Limit Theorem Is Not Your Friend

    ERIC Educational Resources Information Center

    May, Henry

    2014-01-01

    Interest in variation in program impacts--How big is it? What might explain it?--has inspired recent work on the analysis of data from multi-site experiments. One critical aspect of this problem involves the use of random or fixed effect estimates to visualize the distribution of impact estimates across a sample of sites. Unfortunately, unless the…

  3. A Dicobalt Complex with an Unsymmetrical Quinonoid Bridge Isolated in Three Units of Charge: A Combined Structural, (Spectro)electrochemical, Magnetic and Spectroscopic Study.

    PubMed

    van der Meer, Margarethe; Rechkemmer, Yvonne; Frank, Uta; Breitgoff, Frauke D; Hohloch, Stephan; Su, Cheng-Yong; Neugebauer, Petr; Marx, Raphael; Dörfel, María; van Slageren, Joris; Sarkar, Biprajit

    2016-09-19

    Quinonoid ligands are excellent bridges for generating redox-rich dinuclear assemblies. A large majority of these bridges are symmetrically substituted, with examples of unsymmetrically substituted quinonoid bridges being extremely rare. We present here a dicobalt complex in its various redox states with an unsymmetrically substituted quinonoid bridging ligand. Two homovalent forms and one mixed-valent form have been isolated and characterized by single crystal X-ray diffraction. The complex displays a large comproportionation constant for the mixed-valent state which is three orders of magnitude higher than that observed for the analogous complex with a symmetrically substituted bridge. Results from electrochemistry, UV/Vis/NIR spectroelectrochemistry, SQUID magnetometry, multi-frequency EPR spectroscopy and FIR spectroscopy are used to probe the electronic structures of these complexes. FIR provides direct evidence of exchange coupling. The results presented here display the advantages of using an unsymmetrically substituted bridge: site specific redox chemistry, high thermodynamic stabilization of the mixed-valent form, isolation and crystallization of various redox forms of the complex. This work represents an important step on the way to generating heterodinuclear complexes for use in cooperative catalysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Luminescence profiling of loess-dominated archaeological layers of a Chalcolithic site, Northern Negev Desert fringe, Israel

    NASA Astrophysics Data System (ADS)

    López, Gloria I.; Roskin, Joel; Bee'ri, Ron

    2017-04-01

    This study applies a pulsed-photon Portable OSL Reader (PPSL) in investigating the palaeoenviroment and stages of development of a Chalcolithic site revealed during a salvage excavation. The (Shoqet Junction) site, within late Pleistocene loess-dominated sediment, is adjacent to the meandering and ephemeral Hebron Wadi in the Beer-Sheva Valley, at the fringe of the Northern Negev Desert (Israel). The site intermittently covers approximately 8 hectares and was exposed at 0.3 - 0.5 m depths beneath a plowed field. Five areas were excavated down to 4 meters. The site was dominated by an array of underground facilities: tunnels, (capped) shafts, walls, floors and infilled cavities were found within four main layers. The site includes a mixture of sediments: large amounts of organic material, weathered bricks, a powdery loess-like unit and thin Bk horizons. The artifact assemblage is associated with the Ghassulian culture. The objectives of this multi-parameter study, which combines PPSL luminescence profiling with sedimentological and geomorphic analyses, are to (1) analyze the Chalcolithic palaeoenvironments, aeolian and fluvial processes and location and morphology of streambeds, (2) identify possible deterministic physical influences upon the occupations (3) decipher the natural stratigraphic archive and discriminate between human and natural (aeolian/fluvial) induced sedimentation (4) create relative age profiles based on portable OSL measurements and OSL ages, in order to minimize OSL dating. Three main sections were profiled: a natural section - in order to identify the natural sedimentological regime and two walls of two excavation squares down to the sites' alluvial base. A small section above a prominent Bk horizon was also profiled. Altogether 58 samples were obtained for sediment and PPSL analyses. Luminescence profiles in general fit the stratigraphic breaks and enable discrimination between layers. Plowed and surface loess give low reads. Inverse reads along the profile are partly understood to be due to anthropogenic intervention with the sediment. The study highlights the potential and some of the complexities involved with portable OSL profiling of multi-layer prehistoric sites.

  5. Expansion of the Gateway MultiSite Recombination Cloning Toolkit

    PubMed Central

    Shearin, Harold K.; Dvarishkis, Alisa R.; Kozeluh, Craig D.; Stowers, R. Steven

    2013-01-01

    Precise manipulation of transgene expression in genetic model organisms has led to advances in understanding fundamental mechanisms of development, physiology, and genetic disease. Transgene construction is, however, a precondition of transgene expression, and often limits the rate of experimental progress. Here we report an expansion of the modular Gateway MultiSite recombination-cloning platform for high efficiency transgene assembly. The expansion includes two additional destination vectors and entry clones for the LexA binary transcription system, among others. These new tools enhance the expression levels possible with Gateway MultiSite generated transgenes and make possible the generation of LexA drivers and reporters with Gateway MultiSite cloning. In vivo data from transgenic Drosophila functionally validating each novel component are presented and include neuronal LexA drivers, LexAop2 red and green fluorescent synaptic vesicle reporters, TDC2 and TRH LexA, GAL4, and QF drivers, and LexAop2, UAS, and QUAS channelrhodopsin2 T159C reporters. PMID:24204935

  6. A decision support model for improving a multi-family housing complex based on CO2 emission from electricity consumption.

    PubMed

    Hong, Taehoon; Koo, Choongwan; Kim, Hyunjoong

    2012-12-15

    The number of deteriorated multi-family housing complexes in South Korea continues to rise, and consequently their electricity consumption is also increasing. This needs to be addressed as part of the nation's efforts to reduce energy consumption. The objective of this research was to develop a decision support model for determining the need to improve multi-family housing complexes. In this research, 1664 cases located in Seoul were selected for model development. The research team collected the characteristics and electricity energy consumption data of these projects in 2009-2010. The following were carried out in this research: (i) using the Decision Tree, multi-family housing complexes were clustered based on their electricity energy consumption; (ii) using Case-Based Reasoning, similar cases were retrieved from the same cluster; and (iii) using a combination of Multiple Regression Analysis, Artificial Neural Network, and Genetic Algorithm, the prediction performance of the developed model was improved. The results of this research can be used as follows: (i) as basic research data for continuously managing several energy consumption data of multi-family housing complexes; (ii) as advanced research data for predicting energy consumption based on the project characteristics; (iii) as practical research data for selecting the most optimal multi-family housing complex with the most potential in terms of energy savings; and (iv) as consistent and objective criteria for incentives and penalties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. The late Holocene kauri chronology: assessing the potential of a 4500-year record for palaeoclimate reconstruction

    NASA Astrophysics Data System (ADS)

    Boswijk, G.; Fowler, A. M.; Palmer, J. G.; Fenwick, P.; Hogg, A.; Lorrey, A.; Wunder, J.

    2014-04-01

    Millennial and multi-millennial tree-ring chronologies can provide useful proxy records of past climate, giving insight into a more complete range of natural climate variability prior to the 20th century. Since the 1980s a multi-millennial tree-ring chronology has been developed from kauri (Agathis australis) from the upper North Island, New Zealand. Previous work has demonstrated the sensitivity of kauri to the El Niño-Southern Oscillation (ENSO). Here we present recent additions and extensions to the late Holocene kauri chronology (LHKC), and assess the potential of a composite master chronology, AGAUc13, for palaeoclimate reconstruction. The updated composite kauri chronology now spans 4491 years (2488 BCE-2002 CE) and includes data from 18 modern sites, 25 archaeological sites, and 18 sub-fossil (swamp) kauri sites. Consideration of the composition and statistical quality of AGAUc13 suggests the LHKC has utility for palaeoclimate reconstruction but there are caveats. These include: (a) differences in character between the three assemblages including growth rate and sensitivity; (b) low sample depth and low statistical quality in the 10th-13th century CE, when the record transitions from modern and archaeological material to the swamp kauri; (c) a potential difference in amplitude of the signal in the swamp kauri; (d) a westerly bias in site distribution prior to 911 CE; (e) variable statistical quality across the entire record associated with variable replication; and (f) complex changes in sample depth and tree age and size which may influence centennial scale trends in the data. Further tree ring data are required to improve statistical quality, particularly in the first half of the second millennium CE.

  8. Quantitative Mapping of Matrix Content and Distribution across the Ligament-to-Bone Insertion

    PubMed Central

    Spalazzi, Jeffrey P.; Boskey, Adele L.; Pleshko, Nancy; Lu, Helen H.

    2013-01-01

    The interface between bone and connective tissues such as the Anterior Cruciate Ligament (ACL) constitutes a complex transition traversing multiple tissue regions, including non-calcified and calcified fibrocartilage, which integrates and enables load transfer between otherwise structurally and functionally distinct tissue types. The objective of this study was to investigate region-dependent changes in collagen, proteoglycan and mineral distribution, as well as collagen orientation, across the ligament-to-bone insertion site using Fourier transform infrared spectroscopic imaging (FTIR-I). Insertion site-related differences in matrix content were also evaluated by comparing tibial and femoral entheses. Both region- and site-related changes were observed. Collagen content was higher in the ligament and bone regions, while decreasing across the fibrocartilage interface. Moreover, interfacial collagen fibrils were aligned parallel to the ligament-bone interface near the ligament region, assuming a more random orientation through the bulk of the interface. Proteoglycan content was uniform on average across the insertion, while its distribution was relatively less variable at the tibial compared to the femoral insertion. Mineral was only detected in the calcified interface region, and its content increased exponentially across the mineralized fibrocartilage region toward bone. In addition to new insights into matrix composition and organization across the complex multi-tissue junction, findings from this study provide critical benchmarks for the regeneration of soft tissue-to-bone interfaces and integrative soft tissue repair. PMID:24019964

  9. Understanding the mechanisms of protein-DNA interactions

    NASA Astrophysics Data System (ADS)

    Lavery, Richard

    2004-03-01

    Structural, biochemical and thermodynamic data on protein-DNA interactions show that specific recognition cannot be reduced to a simple set of binary interactions between the partners (such as hydrogen bonds, ion pairs or steric contacts). The mechanical properties of the partners also play a role and, in the case of DNA, variations in both conformation and flexibility as a function of base sequence can be a significant factor in guiding a protein to the correct binding site. All-atom molecular modeling offers a means of analyzing the role of different binding mechanisms within protein-DNA complexes of known structure. This however requires estimating the binding strengths for the full range of sequences with which a given protein can interact. Since this number grows exponentially with the length of the binding site it is necessary to find a method to accelerate the calculations. We have achieved this by using a multi-copy approach (ADAPT) which allows us to build a DNA fragment with a variable base sequence. The results obtained with this method correlate well with experimental consensus binding sequences. They enable us to show that indirect recognition mechanisms involving the sequence dependent properties of DNA play a significant role in many complexes. This approach also offers a means of predicting protein binding sites on the basis of binding energies, which is complementary to conventional lexical techniques.

  10. Multi-Morbidity in Hospitalised Older Patients: Who Are the Complex Elderly?

    PubMed Central

    Ruiz, Milagros; Bottle, Alex; Long, Susannah; Aylin, Paul

    2015-01-01

    Background No formal definition for the “complex elderly” exists; moreover, these older patients with high levels of multi-morbidity are not readily identified as such at point of hospitalisation, thus missing a valuable opportunity to manage the older patient appropriately within the hospital setting. Objectives To empirically identify the complex elderly patient based on degree of multi-morbidity. Design Retrospective observational study using administrative data. Setting English hospitals during the financial year 2012–13. Subjects All admitted patients aged 65 years and over. Methods By using exploratory analysis (correspondence analysis) we identify multi-morbidity groups based on 20 target conditions whose hospital prevalence was ≥ 1%. Results We examined a total of 2788900 hospital admissions. Multi-morbidity was highly prevalent, 62.8% had 2 or more of the targeted conditions while 4.7% had six or more. Multi-morbidity increased with age from 56% (65-69yr age-groups) up to 67% (80-84yr age-group). The average multi-morbidity was 3.2±1.2 (SD). Correspondence analysis revealed 3 distinct groups of older patients. Group 1 (multi-morbidity ≤2), associated with cancer and/or metastasis; Group 2 (multi-morbidity of 3, 4 or 5), associated with chronic pulmonary disease, lung disease, rheumatism and osteoporosis; finally Group 3 with the highest level of multi-morbidity (≥6) and associated with heart failure, cerebrovascular accident, diabetes, hypertension and myocardial infarction. Conclusions By using widely available hospital administrative data, we propose patients in Groups 2 and 3 to be identified as the complex elderly. Identification of multi-morbidity patterns can help to predict the needs of the older patient and improve resource provision. PMID:26716440

  11. Multi-dimensional water quality assessment of an urban drinking water source elucidated by high resolution underwater towed vehicle mapping.

    PubMed

    Lock, Alan; Spiers, Graeme; Hostetler, Blair; Ray, James; Wallschläger, Dirk

    2016-04-15

    Spatial surveys of Ramsey Lake, Sudbury, Ontario water quality were conducted using an innovative underwater towed vehicle (UTV) equipped with a multi-parameter probe providing real-time water quality data. The UTV revealed underwater vent sites through high resolution monitoring of different spatial chemical characteristics using common sensors (turbidity, chloride, dissolved oxygen, and oxidation/reduction sensors) that would not be feasible with traditional water sampling methods. Multi-parameter probe vent site identification is supported by elevated alkalinity and silica concentrations at these sites. The identified groundwater vent sites appear to be controlled by bedrock fractures that transport water from different sources with different contaminants of concern. Elevated contaminants, such as, arsenic and nickel and/or nutrient concentrations are evident at the vent sites, illustrating the potential of these sources to degrade water quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 76 FR 80385 - Draft Environmental Impact Statement and Proposed Maricopa Sun Solar Complex Multi-Species...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ...-FXES11120800000F2-123] Draft Environmental Impact Statement and Proposed Maricopa Sun Solar Complex Multi-Species... National Environmental Policy Act for the proposed Maricopa Sun Solar Complex Habitat Conservation Plan... construction, operation, and decommissioning of a 700 megawatt photo-voltaic power generating facility and...

  13. NHEERL CONTAMINATED SEDIMENT RESEARCH MULTI-YEAR IMPLEMENTATION PLAN (2005)

    EPA Science Inventory

    ORD has developed a multi-year plan (MYP) called the Contaminated Sites MYP to address the research needs of EPA's Office of Superfund Remediation and Technology Innovation (OSRTI). One of the long-term goals of the Contaminated Sites MYP relates to contaminated sediments, and t...

  14. The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.

    PubMed

    Lucato, Christina M; Halls, Michelle L; Ooms, Lisa M; Liu, Heng-Jia; Mitchell, Christina A; Whisstock, James C; Ellisdon, Andrew M

    2015-08-21

    The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Adsorption of MCPA on goethite and humic acid-coated goethite.

    PubMed

    Iglesias, A; López, R; Gondar, D; Antelo, J; Fiol, S; Arce, F

    2010-03-01

    Anionic pesticides are adsorbed on the mineral oxide fraction of the soil surface but considerably less on the organic fraction, so that the presence of organic matter causes a decrease in the amount of pesticide adsorbed, and may affect the mechanism of adsorption. In the present study we investigated the adsorption of the weak acid pesticide MCPA on the surface of goethite and of humic acid-coated goethite, selected as models of the mineral oxide fraction and organic components present in soil systems. Adsorption of the anionic form of the pesticide on goethite fitted an S-type isotherm and the amount adsorbed increased as the ionic strength decreased and the pH of the medium decreased. Application of the charge distribution multi site complexation model (CD-MUSIC model) enabled interpretation of the results, which suggested the formation of inner and outer sphere complexes between the pesticide and the singly-coordinated surface sites of goethite. Less pesticide was adsorbed on the humic acid-coated goethite than on the bare goethite and the pattern fitted an L-type isotherm, which indicates a change in the mechanism of adsorption. Simplified calculations with the CD-MUSIC model enabled interpretation of the results, which suggested that the pesticide molecules form the same type of surface complexes as in the previous case. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  16. Activity of N-coordinated multi-metal-atom active site structures for Pt-free oxygen reduction reaction catalysis: Role of *OH ligands

    DOE PAGES

    Holby, Edward F.; Taylor, Christopher D.

    2015-03-19

    We report calculated oxygen reduction reaction energy pathways on multi-metal-atom structures that have previously been shown to be thermodynamically favorable. We predict that such sites have the ability to spontaneously cleave the O₂ bond and then will proceed to over-bind reaction intermediates. In particular, the *OH bound state has lower energy than the final 2 H₂O state at positive potentials. Contrary to traditional surface catalysts, this *OH binding does not poison the multi-metal-atom site but acts as a modifying ligand that will spontaneously form in aqueous environments leading to new active sites that have higher catalytic activities. These *OH boundmore » structures have the highest calculated activity to date.« less

  17. Adeno-associated virus-2 and its primary cellular receptor-Cryo-EM structure of a heparin complex

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

    O'Donnell, Jason; Taylor, Kenneth A.; Chapman, Michael S.

    2009-03-15

    Adeno-associated virus serotype 2 (AAV-2) is a leading candidate vector for gene therapy. Cell entry starts with attachment to a primary receptor, Heparan Sulfate Proteoglycan (HSPG) before binding to a co-receptor. Here, cryo-electron microscopy provides direct visualization of the virus-HSPG interactions. Single particle analysis was performed on AAV-2 complexed with a 17 kDa heparin fragment at 8.3 A resolution. Heparin density covers the shoulder of spikes surrounding viral 3-fold symmetry axes. Previously implicated, positively charged residues R{sub 448/585}, R{sub 451/588} and R{sub 350/487} from another subunit cluster at the center of the heparin footprint. The footprint is much more extensivemore » than apparent through mutagenesis, including R{sub 347/484}, K{sub 395/532} and K{sub 390/527} that are more conserved, but whose roles have been controversial. It also includes much of a region proposed as a co-receptor site, because prior studies had not revealed heparin interactions. Heparin density bridges over the viral 3-fold axes, indicating multi-valent attachment to symmetry-related binding sites.« less

  18. Type III restriction endonucleases are heterotrimeric: comprising one helicase–nuclease subunit and a dimeric methyltransferase that binds only one specific DNA

    PubMed Central

    Butterer, Annika; Pernstich, Christian; Smith, Rachel M.; Sobott, Frank; Szczelkun, Mark D.; Tóth, Júlia

    2014-01-01

    Fundamental aspects of the biochemistry of Type III restriction endonucleases remain unresolved despite being characterized by numerous research groups in the past decades. One such feature is the subunit stoichiometry of these hetero-oligomeric enzyme complexes, which has important implications for the reaction mechanism. In this study, we present a series of results obtained by native mass spectrometry and size exclusion chromatography with multi-angle light scattering consistent with a 1:2 ratio of Res to Mod subunits in the EcoP15I, EcoPI and PstII complexes as the main holoenzyme species and a 1:1 stoichiometry of specific DNA (sDNA) binding by EcoP15I and EcoPI. Our data are also consistent with a model where ATP hydrolysis activated by recognition site binding leads to release of the enzyme from the site, dissociation from the substrate via a free DNA end and cleavage of the DNA. These results are discussed critically in the light of the published literature, aiming to resolve controversies and discuss consequences in terms of the reaction mechanism. PMID:24510100

  19. Multi-spectroscopic and voltammetric evidences for binding, conformational changes of bovine serum albumin with thiamine.

    PubMed

    Bagoji, Atmanand M; Gowda, Jayant I; Gokavi, Naveen M; Nandibewoor, Sharanappa T

    2017-08-01

    The interaction between thiamine hydrochloride (TA) and bovine serum albumin (BSA) was investigated by fluorescence, FTIR, UV-vis spectroscopic and cyclic voltammetric techniques under optimised physiological condition. The fluorescence intensity of BSA is gradually decreased upon addition of TA due to the formation of a BSA-TA complex. The binding parameters were evaluated and their behaviour at different temperatures was analysed. The quenching constants (K sv ) obtained were 2.6 × 10 4 , 2.2 × 10 4 and 2.0 × 10 4  L mol -1 at 288, 298 and 308 K, respectively. The binding mechanism was static-type quenching. The values of ΔH° and ΔS° were found to be 26.87 kJ mol -1 and 21.3 J K -1  mol -1 , and indicated that electrostatic interaction was the principal intermolecular force. The changes in the secondary structure of BSA upon interaction with TA were confirmed by synchronous and 3-D spectral results. Site probe studies reveal that TA is located in site I of BSA. The effects of some common metal ions on binding of BSA-TA complex were also investigated.

  20. "Less Clicking, More Watching": Results from the User-Centered Design of a Multi-Institutional Web Site for Art and Culture.

    ERIC Educational Resources Information Center

    Vergo, John; Karat, Clare-Marie; Karat, John; Pinhanez, Claudio; Arora, Renee; Cofino, Thomas; Riecken, Doug; Podlaseck, Mark

    This paper summarizes a 10-month long research project conducted at the IBM T.J. Watson Research Center aimed at developing the design concept of a multi-institutional art and culture web site. The work followed a user-centered design (UCD) approach, where interaction with prototypes and feedback from potential users of the web site were sought…

  1. Multi-Enzyme Complexes in the Thermophilic Archaea: The Effects of Temperature on Stability, Catalysis and Enzyme Interactions in a Multi-Component System

    DTIC Science & Technology

    2012-01-01

    COVERED (From - To) 4. TITLE AND SUBTITLE Multi- enzyme complexes in the thermophilic archaea: The effects of temperature on stability, catalysis and... enzyme interactions in a multi- component system 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-07-1-0058 5c. PROGRAM ELEMENT NUMBER 61102F 6...involves cloning of the genes for the relevant lipoylation enzymes , and characterisation of the protein products 15. SUBJECT TERMS 16. SECURITY

  2. Multi-site study of diffusion metric variability: effects of site, vendor, field strength, and echo time on regions-of-interest and histogram-bin analyses.

    PubMed

    Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

    2016-02-27

    It is now common for magnetic-resonance-imaging (MRI) based multi-site trials to include diffusion-weighted imaging (DWI) as part of the protocol. It is also common for these sites to possess MR scanners of different manufacturers, different software and hardware, and different software licenses. These differences mean that scanners may not be able to acquire data with the same number of gradient amplitude values and number of available gradient directions. Variability can also occur in achievable b-values and minimum echo times. The challenge of a multi-site study then, is to create a common protocol by understanding and then minimizing the effects of scanner variability and identifying reliable and accurate diffusion metrics. This study describes the effect of site, scanner vendor, field strength, and TE on two diffusion metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA) using two common analyses (region-of-interest and mean-bin value of whole brain histograms). The goal of the study was to identify sources of variability in diffusion-sensitized imaging and their influence on commonly reported metrics. The results demonstrate that the site, vendor, field strength, and echo time all contribute to variability in FA and MD, though to different extent. We conclude that characterization of the variability of DTI metrics due to site, vendor, field strength, and echo time is a worthwhile step in the construction of multi-center trials.

  3. Spatial ecological processes and local factors predict the distribution and abundance of spawning by steelhead (Oncorhynchus mykiss) across a complex riverscape

    USGS Publications Warehouse

    Falke, Jeffrey A.; Dunham, Jason B.; Jordan, Christopher E.; McNyset, Kris M.; Reeves, Gordon H.

    2013-01-01

    Processes that influence habitat selection in landscapes involve the interaction of habitat composition and configuration and are particularly important for species with complex life cycles. We assessed the relative influence of landscape spatial processes and local habitat characteristics on patterns in the distribution and abundance of spawning steelhead (Oncorhynchus mykiss), a threatened salmonid fish, across ~15,000 stream km in the John Day River basin, Oregon, USA. We used hurdle regression and a multi-model information theoretic approach to identify the relative importance of covariates representing key aspects of the steelhead life cycle (e.g., site access, spawning habitat quality, juvenile survival) at two spatial scales: within 2-km long survey reaches (local sites) and ecological neighborhoods (5 km) surrounding the local sites. Based on Akaike’s Information Criterion, models that included covariates describing ecological neighborhoods provided the best description of the distribution and abundance of steelhead spawning given the data. Among these covariates, our representation of offspring survival (growing-season-degree-days, °C) had the strongest effect size (7x) relative to other predictors. Predictive performances of model-averaged composite and neighborhood-only models were better than a site-only model based on both occurrence (percentage of sites correctly classified = 0.80±0.03 SD, 0.78±0.02 vs. 0.62±0.05, respectively) and counts (root mean square error = 3.37, 3.93 vs. 5.57, respectively). The importance of both temperature and stream flow for steelhead spawning suggest this species may be highly sensitive to impacts of land and water uses, and to projected climate impacts in the region and that landscape context, complementation, and connectivity will drive how this species responds to future environments.

  4. Applying the institutional review board data repository approach to manage ethical considerations in evaluating and studying medical education

    PubMed Central

    Thayer, Erin K.; Rathkey, Daniel; Miller, Marissa Fuqua; Palmer, Ryan; Mejicano, George C.; Pusic, Martin; Kalet, Adina; Gillespie, Colleen; Carney, Patricia A.

    2016-01-01

    Issue Medical educators and educational researchers continue to improve their processes for managing medical student and program evaluation data using sound ethical principles. This is becoming even more important as curricular innovations are occurring across undergraduate and graduate medical education. Dissemination of findings from this work is critical, and peer-reviewed journals often require an institutional review board (IRB) determination. Approach IRB data repositories, originally designed for the longitudinal study of biological specimens, can be applied to medical education research. The benefits of such an approach include obtaining expedited review for multiple related studies within a single IRB application and allowing for more flexibility when conducting complex longitudinal studies involving large datasets from multiple data sources and/or institutions. In this paper, we inform educators and educational researchers on our analysis of the use of the IRB data repository approach to manage ethical considerations as part of best practices for amassing, pooling, and sharing data for educational research, evaluation, and improvement purposes. Implications Fostering multi-institutional studies while following sound ethical principles in the study of medical education is needed, and the IRB data repository approach has many benefits, especially for longitudinal assessment of complex multi-site data. PMID:27443407

  5. A theory for protein dynamics: Global anisotropy and a normal mode approach to local complexity

    NASA Astrophysics Data System (ADS)

    Copperman, Jeremy; Romano, Pablo; Guenza, Marina

    2014-03-01

    We propose a novel Langevin equation description for the dynamics of biological macromolecules by projecting the solvent and all atomic degrees of freedom onto a set of coarse-grained sites at the single residue level. We utilize a multi-scale approach where molecular dynamic simulations are performed to obtain equilibrium structural correlations input to a modified Rouse-Zimm description which can be solved analytically. The normal mode solution provides a minimal basis set to account for important properties of biological polymers such as the anisotropic global structure, and internal motion on a complex free-energy surface. This multi-scale modeling method predicts the dynamics of both global rotational diffusion and constrained internal motion from the picosecond to the nanosecond regime, and is quantitative when compared to both simulation trajectory and NMR relaxation times. Utilizing non-equilibrium sampling techniques and an explicit treatment of the free-energy barriers in the mode coordinates, the model is extended to include biologically important fluctuations in the microsecond regime, such as bubble and fork formation in nucleic acids, and protein domain motion. This work supported by the NSF under the Graduate STEM Fellows in K-12 Education (GK-12) program, grant DGE-0742540 and NSF grant DMR-0804145, computational support from XSEDE and ACISS.

  6. Generalist solutions to complex problems: generating practice-based evidence - the example of managing multi-morbidity

    PubMed Central

    2013-01-01

    Background A growing proportion of people are living with long term conditions. The majority have more than one. Dealing with multi-morbidity is a complex problem for health systems: for those designing and implementing healthcare as well as for those providing the evidence informing practice. Yet the concept of multi-morbidity (the presence of >2 diseases) is a product of the design of health care systems which define health care need on the basis of disease status. So does the solution lie in an alternative model of healthcare? Discussion Strengthening generalist practice has been proposed as part of the solution to tackling multi-morbidity. Generalism is a professional philosophy of practice, deeply known to many practitioners, and described as expertise in whole person medicine. But generalism lacks the evidence base needed by policy makers and planners to support service redesign. The challenge is to fill this practice-research gap in order to critically explore if and when generalist care offers a robust alternative to management of this complex problem. We need practice-based evidence to fill this gap. By recognising generalist practice as a ‘complex intervention’ (intervening in a complex system), we outline an approach to evaluate impact using action-research principles. We highlight the implications for those who both commission and undertake research in order to tackle this problem. Summary Answers to the complex problem of multi-morbidity won’t come from doing more of the same. We need to change systems of care, and so the systems for generating evidence to support that care. This paper contributes to that work through outlining a process for generating practice-based evidence of generalist solutions to the complex problem of person-centred care for people with multi-morbidity. PMID:23919296

  7. Generalist solutions to complex problems: generating practice-based evidence--the example of managing multi-morbidity.

    PubMed

    Reeve, Joanne; Blakeman, Tom; Freeman, George K; Green, Larry A; James, Paul A; Lucassen, Peter; Martin, Carmel M; Sturmberg, Joachim P; van Weel, Chris

    2013-08-07

    A growing proportion of people are living with long term conditions. The majority have more than one. Dealing with multi-morbidity is a complex problem for health systems: for those designing and implementing healthcare as well as for those providing the evidence informing practice. Yet the concept of multi-morbidity (the presence of >2 diseases) is a product of the design of health care systems which define health care need on the basis of disease status. So does the solution lie in an alternative model of healthcare? Strengthening generalist practice has been proposed as part of the solution to tackling multi-morbidity. Generalism is a professional philosophy of practice, deeply known to many practitioners, and described as expertise in whole person medicine. But generalism lacks the evidence base needed by policy makers and planners to support service redesign. The challenge is to fill this practice-research gap in order to critically explore if and when generalist care offers a robust alternative to management of this complex problem. We need practice-based evidence to fill this gap. By recognising generalist practice as a 'complex intervention' (intervening in a complex system), we outline an approach to evaluate impact using action-research principles. We highlight the implications for those who both commission and undertake research in order to tackle this problem. Answers to the complex problem of multi-morbidity won't come from doing more of the same. We need to change systems of care, and so the systems for generating evidence to support that care. This paper contributes to that work through outlining a process for generating practice-based evidence of generalist solutions to the complex problem of person-centred care for people with multi-morbidity.

  8. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

    PubMed Central

    Anastassiadis, Theonie; Deacon, Sean W.; Devarajan, Karthik; Ma, Haiching; Peterson, Jeffrey R.

    2011-01-01

    Small-molecule protein kinase inhibitors are central tools for elucidating cellular signaling pathways and are promising therapeutic agents. Due to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments utilizing these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we profiled the activity of 178 commercially available kinase inhibitors against a panel of 300 recombinant protein kinases using a functional assay. Quantitative analysis revealed complex and often unexpected kinase-inhibitor interactions, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can be used to identify multi-targeted inhibitors of specific, diverse kinases. The results have significant implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments that use them. PMID:22037377

  9. Multi-Site Quality Assurance Project Plan for Wisconsin Public Service Corporation, Peoples Gas Light and Coke Company, and North Shore Gas

    EPA Pesticide Factsheets

    This Multi-Site QAPP presents the organization, data quality objectives (DQOs), a set of anticipated activities, sample analysis, data handling and specific Quality Assurance/Quality Control (QA/QC) procedures associated with Studies done in EPA Region 5

  10. Intercontinental Multi-Domain Monitoring for LHC with perfSONAR

    NASA Astrophysics Data System (ADS)

    Vicinanza, D.

    2012-12-01

    The Large Hadron Collider (LHC) is currently running at CERN in Geneva, Switzerland. Physicists are using LHC to recreate the conditions just after the Big Bang, by colliding two beams of particles and heavy ions head-on at very high energy. The project is generating more than 15 TB of raw data per year, plus 10 TB of “event summary data”. This data is sent out from CERN to eleven Tier 1 research centres in Europe, Asia, and North America using a multi-gigabits Optical Private Network (OPN), the LHCOPN. Tier 1 sites are then connected to 100+ academic and research institutions in the world (the Tier 2s) through a Multipoint to Multipoint network, the LHC Open Network Environment (LHCONE). Network monitoring on such complex network architecture to ensure robust and reliable operation is of crucial importance. The chosen approach for monitoring the OPN and ONE is based on the perfSONAR framework, which is designed for multi-domain monitoring environments. perfSONAR (www.perfsonar.net) is an infrastructure for performance monitoring data exchange between networks, making it easier to solve performance problems occurring between network measurement points interconnected through several network domains.

  11. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity

    PubMed Central

    Miller, Megan B.; Yan, Yan; Machida, Kazuya; Kiraly, Drew D.; Levy, Aaron D.; Wu, Yi I.; Lam, TuKiet T.; Abbott, Thomas; Koleske, Anthony J.; Eipper, Betty A.; Mains, Richard E.

    2017-01-01

    Kalirin7 (Kal7), a postsynaptic Rho GDP/GTP exchange factor (RhoGEF), plays a crucial role in long term potentiation and in the effects of cocaine on behavior and spine morphology. The KALRN gene has been linked to schizophrenia and other disorders of synaptic function. Mass spectrometry was used to quantify phosphorylation at 26 sites in Kal7 from individual adult rat nucleus accumbens and prefrontal cortex before and after exposure to acute or chronic cocaine. Region- and isoform-specific phosphorylation was observed along with region-specific effects of cocaine on Kal7 phosphorylation. Evaluation of the functional significance of multi-site phosphorylation in a complex protein like Kalirin is difficult. With the identification of five tyrosine phosphorylation (pY) sites, a panel of 71 SH2 domains was screened, identifying subsets that interacted with multiple pY sites in Kal7. In addition to this type of reversible interaction, endoproteolytic cleavage by calpain plays an essential role in long-term potentiation. Calpain cleaved Kal7 at two sites, separating the N-terminal domain, which affects spine length, and the PDZ binding motif from the GEF domain. Mutations preventing phosphorylation did not affect calpain sensitivity or GEF activity; phosphomimetic mutations at specific sites altered protein stability, increased calpain sensitivity and reduced GEF activity. PMID:28418645

  12. SpaceX Falcon Heavy Demo Flight - Press Site Activities

    NASA Image and Video Library

    2018-02-06

    The NASA News Center at Kennedy Space Center in Florida is filled with members of the news media awaiting liftoff of the SpaceX Falcon Heavy rocket from Launch Complex 39A. The demonstration flight will be a significant milestone for the world's premier multi-user spaceport. In 2014, NASA signed a property agreement with SpaceX for the use and operation of the center's pad 39A, where the company has launched Falcon 9 rockets and is preparing for the first Falcon Heavy. NASA also has Space Act Agreements in place with partners, such as SpaceX, to provide services needed to process and launch rockets and spacecraft.

  13. SpaceX CRS-14 What's On Board Science Briefing

    NASA Image and Video Library

    2018-04-01

    During the SpaceX CRS-14 "What's On Board?" Science Briefing inside the Kennedy Space Center Press Site Auditorium, members of the media learned about the research headed to the International Space Station aboard the Dragon spacecraft. The briefing focused on several science projects including the Metabolic Tracking experiment; Atmosphere-Space Interactions Monitor (ASIM); Multi-purpose Variable-g Platform (MVP), and Veggie PONDS Validation. The Dragon spacecraft is scheduled to be launched from Space Launch Complex 40 at Cape Canaveral Air Force Station in Florida atop a SpaceX Falcon 9 rocket on the company's 14th Commercial Resupply Services mission to the space station.

  14. SpaceX Falcon Heavy Demo Flight - Press Site Activities

    NASA Image and Video Library

    2018-02-06

    Employees, invited guests and members of the news media await liftoff of the SpaceX Falcon Heavy rocket from Launch Complex 39A at NASA’s Kennedy Space Center in Florida. The demonstration flight is a significant milestone for the world's premier multi-user spaceport. In 2014, NASA signed a property agreement with SpaceX for the use and operation of the center's pad 39A, where the company has launched Falcon 9 rockets and is preparing for the first Falcon Heavy. NASA also has Space Act Agreements in place with partners, such as SpaceX, to provide services needed to process and launch rockets and spacecraft.

  15. An AIE-active boron-difluoride complex: multi-stimuli-responsive fluorescence and application in data security protection.

    PubMed

    Zhu, Xiaolin; Liu, Rui; Li, Yuhao; Huang, Hai; Wang, Qiang; Wang, Danfeng; Zhu, Xuan; Liu, Shishen; Zhu, Hongjun

    2014-11-04

    A novel AIE-active boron-difluoride complex (PTZ) was synthesized which exhibits multi-stimuli responsive characteristics. Its colours and emissions can be switched by mechanical grinding, organic solvent vapours and acid/base vapours. This complex can be utilized in data encryption and decryption based on the protonation-deprotonation effect.

  16. Minimizing impacts of land use change on ecosystem services using multi-criteria heuristic analysis.

    PubMed

    Keller, Arturo A; Fournier, Eric; Fox, Jessica

    2015-06-01

    Development of natural landscapes to support human activities impacts the capacity of the landscape to provide ecosystem services. Typically, several ecosystem services are impacted at a single development site and various footprint scenarios are possible, thus a multi-criteria analysis is needed. Restoration potential should also be considered for the area surrounding the permanent impact site. The primary objective of this research was to develop a heuristic approach to analyze multiple criteria (e.g. impacts to various ecosystem services) in a spatial configuration with many potential development sites. The approach was to: (1) quantify the magnitude of terrestrial ecosystem service (biodiversity, carbon sequestration, nutrient and sediment retention, and pollination) impacts associated with a suite of land use change scenarios using the InVEST model; (2) normalize results across categories of ecosystem services to allow cross-service comparison; (3) apply the multi-criteria heuristic algorithm to select sites with the least impact to ecosystem services, including a spatial criterion (separation between sites). As a case study, the multi-criteria impact minimization algorithm was applied to InVEST output to select 25 potential development sites out of 204 possible locations (selected by other criteria) within a 24,000 ha property. This study advanced a generally applicable spatial multi-criteria approach for 1) considering many land use footprint scenarios, 2) balancing impact decisions across a suite of ecosystem services, and 3) determining the restoration potential of ecosystem services after impacts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Quantifying cadherin mechanotransduction machinery assembly/disassembly dynamics using fluorescence covariance analysis.

    PubMed

    Vedula, Pavan; Cruz, Lissette A; Gutierrez, Natasha; Davis, Justin; Ayee, Brian; Abramczyk, Rachel; Rodriguez, Alexis J

    2016-06-30

    Quantifying multi-molecular complex assembly in specific cytoplasmic compartments is crucial to understand how cells use assembly/disassembly of these complexes to control function. Currently, biophysical methods like Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy provide quantitative measurements of direct protein-protein interactions, while traditional biochemical approaches such as sub-cellular fractionation and immunoprecipitation remain the main approaches used to study multi-protein complex assembly/disassembly dynamics. In this article, we validate and quantify multi-protein adherens junction complex assembly in situ using light microscopy and Fluorescence Covariance Analysis. Utilizing specific fluorescently-labeled protein pairs, we quantified various stages of adherens junction complex assembly, the multiprotein complex regulating epithelial tissue structure and function following de novo cell-cell contact. We demonstrate: minimal cadherin-catenin complex assembly in the perinuclear cytoplasm and subsequent localization to the cell-cell contact zone, assembly of adherens junction complexes, acto-myosin tension-mediated anchoring, and adherens junction maturation following de novo cell-cell contact. Finally applying Fluorescence Covariance Analysis in live cells expressing fluorescently tagged adherens junction complex proteins, we also quantified adherens junction complex assembly dynamics during epithelial monolayer formation.

  18. Excitation energy transfer in photosynthetic protein-pigment complexes

    NASA Astrophysics Data System (ADS)

    Yeh, Shu-Hao

    Quantum biology is a relatively new research area which investigates the rules that quantum mechanics plays in biology. One of the most intriguing systems in this field is the coherent excitation energy transport (EET) in photosynthesis. In this document I will discuss the theories that are suitable for describing the photosynthetic EET process and the corresponding numerical results on several photosynthetic protein-pigment complexes (PPCs). In some photosynthetic EET processes, because of the electronic coupling between the chromophores within the system is about the same order of magnitude as system-bath coupling (electron-phonon coupling), a non-perturbative method called hierarchy equation of motion (HEOM) is applied to study the EET dynamics. The first part of this thesis includes brief introduction and derivation to the HEOM approach. The second part of this thesis the HEOM method will be applied to investigate the EET process within the B850 ring of the light harvesting complex 2 (LH2) from purple bacteria, Rhodopseudomonas acidophila. The dynamics of the exciton population and coherence will be analyzed under different initial excitation configurations and temperatures. Finally, how HEOM can be implemented to simulate the two-dimensional electronic spectra of photosynthetic PPCs will be discussed. Two-dimensional electronic spectroscopy is a crucial experimental technique to probe EET dynamics in multi-chromophoric systems. The system we are interested in is the 7-chromophore Fenna-Matthews-Olson (FMO) complex from green sulfur bacteria, Prosthecochloris aestuarii. Recent crystallographic studies report the existence of an additional (eighth) chromophore in some of the FMO monomers. By applying HEOM we are able to calculate the two-dimensional electronic spectra of the 7-site and 8-site FMO complexes and investigate the functionality of the eighth chromophore.

  19. Structural Asymmetry of the Terminal Catalytic Complex in Selenocysteine Synthesis*

    PubMed Central

    French, Rachel L.; Gupta, Nirupama; Copeland, Paul R.; Simonović, Miljan

    2014-01-01

    Selenocysteine (Sec), the 21st amino acid, is synthesized from a serine precursor in a series of reactions that require selenocysteine tRNA (tRNASec). In archaea and eukaryotes, O-phosphoseryl-tRNASec:selenocysteinyl-tRNASec synthase (SepSecS) catalyzes the terminal synthetic reaction during which the phosphoseryl intermediate is converted into the selenocysteinyl moiety while being attached to tRNASec. We have previously shown that only the SepSecS tetramer is capable of binding to and recognizing the distinct fold of tRNASec. Because only two of the four tRNA-binding sites were occupied in the crystal form, a question was raised regarding whether the observed arrangement and architecture faithfully recapitulated the physiologically relevant ribonucleoprotein complex important for selenoprotein formation. Herein, we determined the stoichiometry of the human terminal synthetic complex of selenocysteine by using small angle x-ray scattering, multi-angle light scattering, and analytical ultracentrifugation. In addition, we provided the first estimate of the ratio between SepSecS and tRNASec in vivo. We show that SepSecS preferentially binds one or two tRNASec molecules at a time and that the enzyme is present in large molar excess over the substrate tRNA in vivo. Moreover, we show that in a complex between SepSecS and two tRNAs, one enzyme homodimer plays a role of the noncatalytic unit that positions CCA ends of two tRNASec molecules into the active site grooves of the other, catalytic, homodimer. Finally, our results demonstrate that the previously determined crystal structure represents the physiologically and catalytically relevant complex and suggest that allosteric regulation of SepSecS might play an important role in regulation of selenocysteine and selenoprotein synthesis. PMID:25190812

  20. Characterisation of recirculation zones in complex terrain using multi-lidar measurements

    NASA Astrophysics Data System (ADS)

    Menke, R.; Mann, J.; Vasiljevic, N.

    2017-12-01

    Wind fields in complex terrain show a higher complexity compared to sites with simpler geometries. It is imperative to understand well the characteristics of complex flows to account for them during the site validation to ensure the wind turbines can withstand the local flow conditions. This study focuses on the description of recirculation zones occurring on lee sides of hills. The flow recirculation can have a significant impact on the success of wind energy projects since it represents one of the main contributors to the turbulence generation. An extensive dataset of observation of flow over complex terrain is available from the Perdigão 2017 field campaign (https://www.nature.com/news/world-s-largest-wind-mapping-project-spins-up-in-portugal-1.21481). A setup of 8 long-range WindScanners (Vasiljević et al., 2016), scanning lidars deployed by DTU performed RHI scans at several positions along two parallel ridges probing the flow field in two vertical planes, in addition data from several meteorological masts is available. With the above-mentioned lidar setup we achieved simultaneous dual-Doppler scans of the recirculation zone at three positions and simultaneous observations of recirculation behind two parallel ridges. Methods are developed to identify and define the extent of recirculation bubbles. Different parameters are defined to characterise the dimensions of the recirculation zone. The change of these parameters along the ridges is studied. In particular, the impact of atmospheric stability and the changes of the wind field at the position of the downwind ridge are investigated. Furthermore, the geometry of the recirculation zone for different wind directions and in connection to the upstream wind conditions is investigated.

  1. KSC-98pc1882

    NASA Image and Video Library

    1998-12-18

    Federal, state, NASA, KSC and Space Florida Authority (SFA) officials dig in at the planned site of a multi-purpose hangar, phase one of the Reusable Launch Vehicle (RLV) Support Complex to be built near the Shuttle Landing Facility. From left, they are a representative from Rush Construction; Ed O'Connor, executive director of the Spaceport Florida Authority (SFA); Stephen T. Black, Lockheed Martin technical operations program manager; Warren Wiley, deputy director of engineering development; Tom Best, district director, representing U.S. Congressman Dave Weldon; Roy Bridges, director, Kennedy Space Center; Bill Posey, 32nd district representative; Randy Ball, state representative; Charlie Bronson, state senator; Donald McMonagle, manager of launch integration; and John London, Marshall Space Flight Center X-34 program manager. The new complex is jointly funded by SFA, NASA's Space Shuttle Program and Kennedy Space Center. It is intended to support the Space Shuttle and other RLV and X-vehicle systems. Completion is expected by the year 2000

  2. Impact of Robotic Surgery on Decision Making: Perspectives of Surgical Teams

    PubMed Central

    Randell, Rebecca; Alvarado, Natasha; Honey, Stephanie; Greenhalgh, Joanne; Gardner, Peter; Gill, Arron; Jayne, David; Kotze, Alwyn; Pearman, Alan; Dowding, Dawn

    2015-01-01

    There has been rapid growth in the purchase of surgical robots in both North America and Europe in recent years. Whilst this technology promises many benefits for patients, the introduction of such a complex interactive system into healthcare practice often results in unintended consequences that are difficult to predict. Decision making by surgeons during an operation is affected by variables including tactile perception, visual perception, motor skill, and instrument complexity, all of which are changed by robotic surgery, yet the impact of robotic surgery on decision making has not been previously studied. Drawing on the approach of realist evaluation, we conducted a multi-site interview study across nine hospitals, interviewing 44 operating room personnel with experience of robotic surgery to gather their perspectives on how robotic surgery impacts surgeon decision making. The findings reveal both potential benefits and challenges of robotic surgery for decision making. PMID:26958244

  3. Impact of Robotic Surgery on Decision Making: Perspectives of Surgical Teams.

    PubMed

    Randell, Rebecca; Alvarado, Natasha; Honey, Stephanie; Greenhalgh, Joanne; Gardner, Peter; Gill, Arron; Jayne, David; Kotze, Alwyn; Pearman, Alan; Dowding, Dawn

    2015-01-01

    There has been rapid growth in the purchase of surgical robots in both North America and Europe in recent years. Whilst this technology promises many benefits for patients, the introduction of such a complex interactive system into healthcare practice often results in unintended consequences that are difficult to predict. Decision making by surgeons during an operation is affected by variables including tactile perception, visual perception, motor skill, and instrument complexity, all of which are changed by robotic surgery, yet the impact of robotic surgery on decision making has not been previously studied. Drawing on the approach of realist evaluation, we conducted a multi-site interview study across nine hospitals, interviewing 44 operating room personnel with experience of robotic surgery to gather their perspectives on how robotic surgery impacts surgeon decision making. The findings reveal both potential benefits and challenges of robotic surgery for decision making.

  4. A decision support tool to prioritize risk management options for contaminated sites.

    PubMed

    Sorvari, Jaana; Seppälä, Jyri

    2010-03-15

    The decisions on risk management (RM) of contaminated sites in Finland have typically been driven by practical factors such as time and money. However, RM is a multifaceted task that generally involves several additional determinants, e.g. performance and environmental effects of remediation methods, psychological and social factors. Therefore, we adopted a multi-criteria decision analysis approach and developed a decision support tool (DST) that is viable in decision-making in such a complex situation. The basic components of the DST are based on the Dutch REC system. However, our DST is more case-specific and allows the consideration of the type, magnitude and scale of contamination, land use, environmental conditions and socio-cultural aspects (e.g. loss of cultural heritage, image aspects). The construction of the DST was started by structuring the decision problem using a value tree. Based on this work we adopted the Multi-Attribute Value Theory (MAVT) for data aggregation. The final DST was demonstrated by two model sites for which the RM alternatives and site-specific data were created on the basis of factual remediation projects and by interviewing experts. The demonstration of the DST was carried out in a workshop where representatives of different stakeholders were requested to rank and weight the decision criteria involved. To get information on the consistency of the ranking of the RM alternatives, we used different weighting techniques (ratio estimation and pair-wise weighting) and alternative ways to treat individual respondents' weights in calculating the preference scores for each RM alternative. These dissimilar approaches resulted in some differences in the preference order of the RM alternatives. The demonstration showed that attention has to be paid to the proper description of the site, the principles of the procedure and the decision criteria. Nevertheless, the procedure proved to enable efficient communication between different stakeholders and the identification of the preferred RM option.

  5. Project Anqa: Digitizing and Documenting Cultural Heritage in the Middle East

    NASA Astrophysics Data System (ADS)

    Akhtar, S.; Akoglu, G.; Simon, S.; Rushmeier, H.

    2017-08-01

    The practice of digitizing cultural heritage sites is gaining ground among conservation scientists and scholars in architecture, art history, computer science, and related fields. Recently, the location of such sites in areas of intense conflict has highlighted the urgent need for documenting cultural heritage for the purposes of preservation and posterity. The complex histories of such sites requires more than just their digitization, and should also include the meaningful interpretation of buildings and their surroundings with respect to context and intangible values. Project Anqa is an interdisciplinary and multi-partner effort that goes beyond simple digitization to record at-risk heritage sites throughout the Middle East and Saharan Africa, most notably in Syria and Iraq, before they are altered or destroyed. Through a collaborative process, Anqa assembles documentation, historically contextualizes it, and makes data accessible and useful for scholars, peers, and the wider public through state-of-the-art tools. The aim of the project is to engage in capacity-building on the ground in Syria and Iraq, as well as to create an educational web platform that informs viewers about cultural heritage in the region through research, digital storytelling, and the experience of virtual environments.

  6. Intraclass Correlations for Three-Level Multi-Site Cluster-Randomized Trials of Science Achievement

    ERIC Educational Resources Information Center

    Westine, Carl D.

    2015-01-01

    A cluster-randomized trial (CRT) relies on random assignment of intact clusters to treatment conditions, such as classrooms or schools (Raudenbush & Bryk, 2002). One specific type of CRT, a multi-site CRT (MSCRT), is commonly employed in educational research and evaluation studies (Spybrook & Raudenbush, 2009; Spybrook, 2014; Bloom,…

  7. A Multi-Site Study on Medical School Selection, Performance, Motivation and Engagement

    ERIC Educational Resources Information Center

    Wouters, A.; Croiset, G.; Schripsema, N. R.; Cohen-Schotanus, J.; Spaai, G. W.; Hulsman, R. L.; Kusurkar, R. A.

    2017-01-01

    Medical schools seek ways to improve their admissions strategies, since the available methods prove to be suboptimal for selecting the best and most motivated students. In this multi-site cross-sectional questionnaire study, we examined the value of (different) selection procedures compared to a weighted lottery procedure, which includes direct…

  8. Factors Influencing Teachers' Technology Self-Efficacy: A Case Study

    ERIC Educational Resources Information Center

    Farah, Amy Caroline

    2012-01-01

    Factors influencing teachers' levels of technology self-efficacy were examined through a qualitative multi-site, multi-subject case study research design. An initial survey was administered to all full-time, certified teachers at three school sites in order to gauge teachers' current level of technology self-efficacy. From that…

  9. How Does a Multi-Site Institution Plan Effectively?

    ERIC Educational Resources Information Center

    Jefferson, Curtis F.

    A multi-site college plans effectively by having in place planning and evaluation systems that enhance its capability to respond effectively to changes in the environment in order to continue to provide high quality educational programs and services for the people in its service area. The effectiveness of these systems is dependent on clearly…

  10. Designing Multi-Channel Web Frameworks for Cultural Tourism Applications: The MUSE Case Study.

    ERIC Educational Resources Information Center

    Garzotto, Franca; Salmon, Tullio; Pigozzi, Massimiliano

    A framework for the design of multi-channel (MC) applications in the cultural tourism domain is presented. Several heterogeneous interface devices are supported including location-sensitive mobile units, on-site stationary devices, and personalized CDs that extend the on-site experience beyond the visit time thanks to personal memories gathered…

  11. 77 FR 4368 - ArcelorMittal, Including Workers Whose Unemployment Insurance (UI) Wages Are Reported Through...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ...- Site Leased Workers From Adecco, ESW, Inc., Guardsmark, Hudson Global Resources, Multi Serv, and Quaker... include on-site leased workers from Multi Serv and Quaker Chemical. The notices were published in the... some workers separated from employment at the Hennepin, Illinois location of ArcelorMittal had their...

  12. Nonlinear instabilities of multi-site breathers in Klein-Gordon lattices

    DOE PAGES

    Cuevas-Maraver, Jesus; Kevrekidis, Panayotis G.; Pelinovsky, Dmitry E.

    2016-08-01

    Here, we explore the possibility of multi-site breather states in a nonlinear Klein–Gordon lattice to become nonlinearly unstable, even if they are found to be spectrally stable. The mechanism for this nonlinear instability is through the resonance with the wave continuum of a multiple of an internal mode eigenfrequency in the linearization of excited breather states. For the nonlinear instability, the internal mode must have its Krein signature opposite to that of the wave continuum. This mechanism is not only theoretically proposed, but also numerically corroborated through two concrete examples of the Klein–Gordon lattice with a soft (Morse) and amore » hard (Φ 4) potential. Compared to the case of the nonlinear Schrödinger lattice, the Krein signature of the internal mode relative to that of the wave continuum may change depending on the period of the multi-site breather state. For the periods for which the Krein signatures of the internal mode and the wave continuum coincide, multi-site breather states are observed to be nonlinearly stable.« less

  13. Caught in the Act: 1.5 Å Resolution Crystal Structures of the HIV-1 Protease and the I54V Mutant Reveal a Tetrahedral Reaction Intermediate

    PubMed Central

    Kovalevsky, Andrey Y.; Chumanevich, Alexander A.; Liu, Fengling; Louis, John M.; Weber, Irene T.

    2008-01-01

    HIV-1 protease (PR) is the target for several important antiviral drugs used in AIDS therapy. The drugs bind inside the active-site cavity of PR where normally the viral poly-protein substrate is bound and hydrolyzed. We report two high resolution crystal structures of wild-type PR (PRWT) and the multi-drug resistant variant with the I54V mutation (PRI54V) in complex with a peptide at 1.46 Å and 1.50 Å resolution, respectively. The peptide forms a gem-diol tetrahedral reaction intermediate (TI) in the crystal structures. Distinctive interactions are observed for the TI binding in the active site cavity of PRWT and PRI54V. The mutant PRI54V /TI complex has lost water-mediated hydrogen bond interactions with the amides of Ile 50 and 50′ in the flap. Hence, the structures provide insight into the mechanism of drug resistance arising from this mutation. The structures also illustrate an intermediate state in the hydrolysis reaction. One of the gem-diol hydroxide groups in the PRWT complex forms a very short (2.3 Å) hydrogen bond with the outer carboxylate oxygen of Asp25. Quantum chemical calculations based on this TI structure are consistent with protonation of the inner carboxylate oxygen of Asp25′, in contrast to several theoretical studies. These TI complexes and quantum calculations are discussed in relation to the chemical mechanism of the peptide bond hydrolysis catalyzed by PR. PMID:18052235

  14. Shared active site architecture between archaeal PolD and multi-subunit RNA polymerases revealed by X-ray crystallography.

    PubMed

    Sauguet, Ludovic; Raia, Pierre; Henneke, Ghislaine; Delarue, Marc

    2016-08-22

    Archaeal replicative DNA polymerase D (PolD) constitute an atypical class of DNA polymerases made of a proofreading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2), both with unknown structures. We have determined the crystal structures of Pyrococcus abyssi DP1 and DP2 at 2.5 and 2.2 Å resolution, respectively, revealing a catalytic core strikingly different from all other known DNA polymerases (DNAPs). Rather, the PolD DP2 catalytic core has the same 'double-psi β-barrel' architecture seen in the RNA polymerase (RNAP) superfamily, which includes multi-subunit transcriptases of all domains of life, homodimeric RNA-silencing pathway RNAPs and atypical viral RNAPs. This finding bridges together, in non-viral world, DNA transcription and DNA replication within the same protein superfamily. This study documents further the complex evolutionary history of the DNA replication apparatus in different domains of life and proposes a classification of all extant DNAPs.

  15. Shared active site architecture between archaeal PolD and multi-subunit RNA polymerases revealed by X-ray crystallography

    PubMed Central

    Sauguet, Ludovic; Raia, Pierre; Henneke, Ghislaine; Delarue, Marc

    2016-01-01

    Archaeal replicative DNA polymerase D (PolD) constitute an atypical class of DNA polymerases made of a proofreading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2), both with unknown structures. We have determined the crystal structures of Pyrococcus abyssi DP1 and DP2 at 2.5 and 2.2 Å resolution, respectively, revealing a catalytic core strikingly different from all other known DNA polymerases (DNAPs). Rather, the PolD DP2 catalytic core has the same ‘double-psi β-barrel' architecture seen in the RNA polymerase (RNAP) superfamily, which includes multi-subunit transcriptases of all domains of life, homodimeric RNA-silencing pathway RNAPs and atypical viral RNAPs. This finding bridges together, in non-viral world, DNA transcription and DNA replication within the same protein superfamily. This study documents further the complex evolutionary history of the DNA replication apparatus in different domains of life and proposes a classification of all extant DNAPs. PMID:27548043

  16. Automatic Derivation of Forest Cover and Forest Cover Change Using Dense Multi-Temporal Time Series Data from Landsat and SPOT 5 Take5

    NASA Astrophysics Data System (ADS)

    Storch, Cornelia; Wagner, Thomas; Ramminger, Gernot; Pape, Marlon; Ott, Hannes; Hausler, Thomas; Gomez, Sharon

    2016-08-01

    The paper presents a description of the methods development for an automated processing chain for the classification of Forest Cover and Change based on high resolution multi-temporal time series Landsat and SPOT5Take5 data with focus on the dry forest ecosystems of Africa. The method has been developed within the European Space Agency (ESA) funded Global monitoring for Environment and Security Service Element for Forest Monitoring (GSE FM) project on dry forest areas; the demonstration site selected was in Malawi. The methods are based on the principles of a robust, but still flexible monitoring system, to cope with most complex Earth Observation (EO) data scenarios, varying in terms of data quality, source, accuracy, information content, completeness etc. The method allows automated tracking of change dates, data gap filling and takes into account phenology, seasonality of tree species with respect to leaf fall and heavy cloud cover during the rainy season.

  17. Spatial mapping reveals multi-step pattern of wound healing in Physarum polycephalum

    NASA Astrophysics Data System (ADS)

    Bäuerle, Felix K.; Kramar, Mirna; Alim, Karen

    2017-11-01

    Wounding is a severe impairment of function, especially for an exposed organism like the network-forming true slime mould Physarum polycephalum. The tubular network making up the organism’s body plan is entirely interconnected and shares a common cytoplasm. Oscillatory contractions of the enclosing tube walls drive the shuttle streaming of the cytoplasm. Cytoplasmic flows underlie the reorganization of the network for example by movement toward attractive stimuli or away from repellants. Here, we follow the reorganization of P. polycephalum networks after severe wounding. Spatial mapping of the contraction changes in response to wounding reveal a multi-step pattern. Phases of increased activity alternate with cessation of contractions and stalling of flows, giving rise to coordinated transport and growth at the severing site. Overall, severing surprisingly acts like an attractive stimulus enabling healing of severed tubes. The reproducible cessation of contractions arising during this wound-healing response may open up new venues to investigate the biochemical wiring underlying P. polycephalum’s complex behaviours.

  18. Structural Insights into the Protease-like Antigen Plasmodium falciparum SERA5 and Its Noncanonical Active-Site Serine

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

    Hodder, Anthony N.; Malby, Robyn L.; Clarke, Oliver B.

    The sera genes of the malaria-causing parasite Plasmodium encode a family of unique proteins that are maximally expressed at the time of egress of parasites from infected red blood cells. These multi-domain proteins are unique, containing a central papain-like cysteine-protease fragment enclosed between the disulfide-linked N- and C-terminal domains. However, the central fragment of several members of this family, including serine repeat antigen 5 (SERA5), contains a serine (S596) in place of the active-site cysteine. Here we report the crystal structure of the central protease-like domain of Plasmodium falciparum SERA5, revealing a number of anomalies in addition to the putativemore » nucleophilic serine: (1) the structure of the putative active site is not conducive to binding substrate in the canonical cysteine-protease manner; (2) the side chain of D594 restricts access of substrate to the putative active site; and (3) the S{sub 2} specificity pocket is occupied by the side chain of Y735, reducing this site to a small depression on the protein surface. Attempts to determine the structure in complex with known inhibitors were not successful. Thus, despite having revealed its structure, the function of the catalytic domain of SERA5 remains an enigma.« less

  19. Combining ground penetrating radar and electromagnetic induction for industrial site characterization

    NASA Astrophysics Data System (ADS)

    Van De Vijver, Ellen; Van Meirvenne, Marc; Saey, Timothy; De Smedt, Philippe; Delefortrie, Samuël; Seuntjens, Piet

    2014-05-01

    Industrial sites pose specific challenges to the conventional way of characterizing soil and groundwater properties through borehole drilling and well monitoring. The subsurface of old industrial sites typically exhibits a large heterogeneity resulting from various anthropogenic interventions, such as the dumping of construction and demolition debris and industrial waste. Also larger buried structures such as foundations, utility infrastructure and underground storage tanks are frequently present. Spills and leaks from industrial activities and leaching of buried waste may have caused additional soil and groundwater contamination. Trying to characterize such a spatially heterogeneous medium with a limited number of localized observations is often problematic. The deployment of mobile proximal soil sensors may be a useful tool to fill up the gaps in between the conventional observations, as these enable measuring soil properties in a non-destructive way. However, because the output of most soil sensors is affected by more than one soil property, the application of only one sensor is generally insufficient to discriminate between all contributing factors. To test a multi-sensor approach, we selected a study area which was part of a former manufactured gas plant site located in one of the seaport areas of Belgium. It has a surface area of 3400 m² and was the location of a phosphate production unit that was demolished at the end of the 1980s. Considering the long and complex history of the site we expected to find a typical "industrial" soil. Furthermore, the studied area was located between buildings of the present industry, entailing additional practical challenges such as the presence of active utilities and aboveground obstacles. The area was surveyed using two proximal soil sensors based on two different geophysical methods: ground penetrating radar (GPR), to image contrasts in dielectric permittivity, and electromagnetic induction (EMI), to measure the apparent soil electrical conductivity (ECa) and magnetic susceptibility (MSa). For both methods one of the latest-generation instruments was used. GPR data were collected using a 3d-Radar stepped-frequency system with multi-channel antenna design. For EMI, this was the multi-receiver DUALEM-21S sensor. This sensor contains four different transmitter-receiver coil pair configurations, which allows to record the ECa and MSa for four different soil volumes at the same time, thereby providing information about the vertical variation of these soil properties. Both the EMI and GPR survey were performed in a mobile set-up with real-time georeferencing to obtain a high-resolution coverage of the area. The results of both surveys were validated with conventional site characterization that was conducted for a soil contamination investigation, and ancillary information such as aerial photographs and utility maps. Both methods were compared on their performance in detecting different types of anomalies. We report on the successes and failures with this multi-sensor approach. The authors acknowledge funding by COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar"

  20. A multi-element cosmological model with a complex space-time topology

    NASA Astrophysics Data System (ADS)

    Kardashev, N. S.; Lipatova, L. N.; Novikov, I. D.; Shatskiy, A. A.

    2015-02-01

    Wormhole models with a complex topology having one entrance and two exits into the same space-time of another universe are considered, as well as models with two entrances from the same space-time and one exit to another universe. These models are used to build a model of a multi-sheeted universe (a multi-element model of the "Multiverse") with a complex topology. Spherical symmetry is assumed in all the models. A Reissner-Norström black-hole model having no singularity beyond the horizon is constructed. The strength of the central singularity of the black hole is analyzed.

  1. Stereotypic and complex phrase types provide structural evidence for a multi-message display in humpback whales (Megaptera novaeangliae).

    PubMed

    Murray, Anita; Dunlop, Rebecca A; Noad, Michael J; Goldizen, Anne W

    2018-02-01

    Male humpback whales produce a mating display called "song." Behavioral studies indicate song has inter- and/or intra-sexual functionality, suggesting song may be a multi-message display. Multi-message displays often include stereotypic components that convey group membership for mate attraction and/or male-male interactions, and complex components that convey individual quality for courtship. Humpback whale song contains sounds ("units") arranged into sequences ("phrases"). Repetitions of a specific phrase create a "theme." Within a theme, imperfect phrase repetitions ("phrase variants") create variability among phrases of the same type ("phrase type"). The hypothesis that song contains stereotypic and complex phrase types, structural characteristics consistent with a multi-message display, is investigated using recordings of 17 east Australian males (8:2004, 9:2011). Phrase types are categorized as stereotypic or complex using number of unit types, number of phrase variants, and the proportion of phrases that is unique to an individual versus shared amongst males. Unit types are determined using self-organizing maps. Phrase variants are determined by Levenshtein distances between phrases. Stereotypic phrase types have smaller numbers of unit types and shared phrase variants. Complex phrase types have larger numbers of unit types and unique phrase variants. This study supports the hypothesis that song could be a multi-message display.

  2. Impact of untreated urban waste on the prevalence and antibiotic resistance profiles of human opportunistic pathogens in agricultural soils from Burkina Faso.

    PubMed

    Youenou, Benjamin; Hien, Edmond; Deredjian, Amélie; Brothier, Elisabeth; Favre-Bonté, Sabine; Nazaret, Sylvie

    2016-12-01

    This study examined the long-term effects of the landfill disposal of untreated urban waste for soil fertilization on the prevalence and antibiotic resistance profiles of various human opportunistic pathogens in soils from Burkina Faso. Samples were collected at three sites in the periphery of Ouagadougou during two campaigns in 2008 and 2011. At each site, amendment led to changes in physico-chemical characteristics as shown by the increase in pH, CEC, total C, total N, and metal contents. Similarly, the numbers of total heterotrophic bacteria were higher in the amended fields than in the control ones. No sanitation indicators, i.e., coliforms, Staphylococci, and Enterococci, were detected. Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) were detected at a low level in one amended field. Stenotrophomonas maltophilia was detected from both campaigns at the three sites in the amended fields and only once in an unamended field. Diversity analysis showed some opportunistic pathogen isolates to be closely related to reference clinical strains responsible for nosocomial- or community-acquired infections in Northern countries. Antibiotic resistance tests showed that P. aeruginosa and Bcc isolates had a wild-type phenotype and that most S. maltophilia isolates had a multi-drug resistance profile with resistance to 7 to 15 antibiotics. Then we were able to show that amendment led to an increase of some human opportunistic pathogens including multi-drug resistant isolates. Although the application of untreated urban waste increases both soil organic matter content and therefore soil fertility, the consequences of this practice on human health should be considered.

  3. a Web-Based Interactive Tool for Multi-Resolution 3d Models of a Maya Archaeological Site

    NASA Astrophysics Data System (ADS)

    Agugiaro, G.; Remondino, F.; Girardi, G.; von Schwerin, J.; Richards-Rissetto, H.; De Amicis, R.

    2011-09-01

    Continuous technological advances in surveying, computing and digital-content delivery are strongly contributing to a change in the way Cultural Heritage is "perceived": new tools and methodologies for documentation, reconstruction and research are being created to assist not only scholars, but also to reach more potential users (e.g. students and tourists) willing to access more detailed information about art history and archaeology. 3D computer-simulated models, sometimes set in virtual landscapes, offer for example the chance to explore possible hypothetical reconstructions, while on-line GIS resources can help interactive analyses of relationships and change over space and time. While for some research purposes a traditional 2D approach may suffice, this is not the case for more complex analyses concerning spatial and temporal features of architecture, like for example the relationship of architecture and landscape, visibility studies etc. The project aims therefore at creating a tool, called "QueryArch3D" tool, which enables the web-based visualisation and queries of an interactive, multi-resolution 3D model in the framework of Cultural Heritage. More specifically, a complete Maya archaeological site, located in Copan (Honduras), has been chosen as case study to test and demonstrate the platform's capabilities. Much of the site has been surveyed and modelled at different levels of detail (LoD) and the geometric model has been semantically segmented and integrated with attribute data gathered from several external data sources. The paper describes the characteristics of the research work, along with its implementation issues and the initial results of the developed prototype.

  4. Evaluating a community-based program to improve healthcare quality: research design for the Aligning Forces for Quality initiative.

    PubMed

    Scanlon, Dennis P; Alexander, Jeffrey A; Beich, Jeff; Christianson, Jon B; Hasnain-Wynia, Romana; McHugh, Megan C; Mittler, Jessica N; Shi, Yunfeng; Bodenschatz, Laura J

    2012-09-01

    The Aligning Forces for Quality (AF4Q) initiative is the Robert Wood Johnson Foundation's (RWJF's) signature effort to increase the overall quality of healthcare in targeted communities throughout the country. In addition to sponsoring this 16-site, complex program, the RWJF funds an independent scientific evaluation to support objective research on the initiative's effectiveness and contributions to basic knowledge in 5 core programmatic areas. The research design, data, and challenges faced in the evaluation of this 10-year initiative are discussed. A descriptive overview of the evaluation research design for a multi-site, community based, healthcare quality improvement initiative is provided. The multiphase research design employed by the evaluation team is discussed. Evaluation provides formative feedback to the RWJF, participants, and other interested audiences in real time; develops approaches to assess innovative and under-studied interventions; furthers the analysis and understanding of effective community-based collaborative work in healthcare; and helps to differentiate the various facilitators, barriers, and contextual dimensions that affect the implementation and outcomes of community-based health interventions. The AF4Q initiative is arguably the largest community-level healthcare improvement demonstration in the United States to date; it is being implemented at a time of rapid change in national healthcare policy. The implementation of large-scale, multi-site initiatives is becoming an increasingly common approach for addressing problems in healthcare. The evaluation research design for the AF4Q initiative, and the lessons learned from its approach, may be valuable to others tasked with evaluating similar community-based initiatives.

  5. Effects of synthetic cohesin-containing scaffold protein architecture on binding dockerin-enzyme fusions on the surface of Lactococcus lactis.

    PubMed

    Wieczorek, Andrew S; Martin, Vincent J J

    2012-12-15

    The microbial synthesis of fuels, commodity chemicals, and bioactive compounds necessitates the assemblage of multiple enzyme activities to carry out sequential chemical reactions, often via substrate channeling by means of multi-domain or multi-enzyme complexes. Engineering the controlled incorporation of enzymes in recombinant protein complexes is therefore of interest. The cellulosome of Clostridium thermocellum is an extracellular enzyme complex that efficiently hydrolyzes crystalline cellulose. Enzymes interact with protein scaffolds via type 1 dockerin/cohesin interactions, while scaffolds in turn bind surface anchor proteins by means of type 2 dockerin/cohesin interactions, which demonstrate a different binding specificity than their type 1 counterparts. Recombinant chimeric scaffold proteins containing cohesins of different specificity allow binding of multiple enzymes to specific sites within an engineered complex. We report the successful display of engineered chimeric scaffold proteins containing both type 1 and type 2 cohesins on the surface of Lactococcus lactis cells. The chimeric scaffold proteins were able to form complexes with the Escherichia coli β-glucuronidase fused to either type 1 or type 2 dockerin, and differences in binding efficiencies were correlated with scaffold architecture. We used E. coli β-galactosidase, also fused to type 1 or type 2 dockerins, to demonstrate the targeted incorporation of two enzymes into the complexes. The simultaneous binding of enzyme pairs each containing a different dockerin resulted in bi-enzymatic complexes tethered to the cell surface. The sequential binding of the two enzymes yielded insights into parameters affecting assembly of the complex such as protein size and position within the scaffold. The spatial organization of enzymes into complexes is an important strategy for increasing the efficiency of biochemical pathways. In this study, chimeric protein scaffolds consisting of type 1 and type 2 cohesins anchored on the surface of L. lactis allowed for the controlled positioning of dockerin-fused reporter enzymes onto the scaffolds. By binding single enzymes or enzyme pairs to the scaffolds, our data also suggest that the size and relative positions of enzymes can affect the catalytic profiles of the resulting complexes. These insights will be of great value as we engineer more advanced scaffold-guided protein complexes to optimize biochemical pathways.

  6. Extreme C2 and Multi-Touch, Multi-User Collaborative User Interfaces

    DTIC Science & Technology

    2008-06-01

    Organization: Office of the Chief Engineer , Space and Naval Warfare Systems Center Charleston Address: PO Box 190022 N. Charleston, SC 29419 843...collaborative development technique can increase the adaptability and quality of software, something of high value in the complex domain of enterprise...concept to C2 should be able to produce similar benefits for planning in military operations, particularly complex, multi- faceted operations. This

  7. The opportunities and challenges of multi-site evaluations: lessons from the jail diversion and trauma recovery national cross-site evaluation.

    PubMed

    Stainbrook, Kristin; Penney, Darby; Elwyn, Laura

    2015-06-01

    Multi-site evaluations, particularly of federally funded service programs, pose a special set of challenges for program evaluation. Not only are there contextual differences related to project location, there are often relatively few programmatic requirements, which results in variations in program models, target populations and services. The Jail Diversion and Trauma Recovery-Priority to Veterans (JDTR) National Cross-Site Evaluation was tasked with conducting a multi-site evaluation of thirteen grantee programs that varied along multiple domains. This article describes the use of a mixed methods evaluation design to understand the jail diversion programs and client outcomes for veterans with trauma, mental health and/or substance use problems. We discuss the challenges encountered in evaluating diverse programs, the benefits of the evaluation in the face of these challenges, and offer lessons learned for other evaluators undertaking this type of evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. XML Encoding of Features Describing Rule-Based Modeling of Reaction Networks with Multi-Component Molecular Complexes

    PubMed Central

    Blinov, Michael L.; Moraru, Ion I.

    2011-01-01

    Multi-state molecules and multi-component complexes are commonly involved in cellular signaling. Accounting for molecules that have multiple potential states, such as a protein that may be phosphorylated on multiple residues, and molecules that combine to form heterogeneous complexes located among multiple compartments, generates an effect of combinatorial complexity. Models involving relatively few signaling molecules can include thousands of distinct chemical species. Several software tools (StochSim, BioNetGen) are already available to deal with combinatorial complexity. Such tools need information standards if models are to be shared, jointly evaluated and developed. Here we discuss XML conventions that can be adopted for modeling biochemical reaction networks described by user-specified reaction rules. These could form a basis for possible future extensions of the Systems Biology Markup Language (SBML). PMID:21464833

  9. Observations and model predictions of water skin temperatures at MTI core site lakes and reservoirs

    NASA Astrophysics Data System (ADS)

    Garrett, Alfred J.; Kurzeja, Robert J.; O'Steen, Byron L.; Parker, Matthew J.; Pendergast, Malcolm M.; Villa-Aleman, Eliel; Pagnutti, Mary A.

    2001-08-01

    The Savannah River Technology Center (SRTC) measured water skin temperatures at four of the Multi-spectral Thermal Imager (MTI) core sites. The depression of the skin temperature relative to the bulk water temperature ((Delta) T) a few centimeters below the surface is a complex function of the weather conditions, turbulent mixing in the water and the bulk water temperature. Observed skin temperature depressions range from near zero to more than 1.0 degree(s)C. Skin temperature depressions tend to be larger when the bulk water temperature is high, but large depressions were also observed in cool bodies of water in calm conditions at night. We compared (Delta) T predictions from three models (SRTC, Schlussel and Wick) against measured (Delta) T's from 15 data sets taken at the MTI core sites. The SRTC and Wick models performed somewhat better than the Schlussel model, with RMSE and average absolute errors of about 0.2 degree(s)C, relative to 0.4 degree(s)C for the Schlussel model. The average observed (Delta) T for all 15 databases was -0.7 degree(s)C.

  10. A multi-disciplinary approach for the structural monitoring of Cultural Heritages in a seismic area

    NASA Astrophysics Data System (ADS)

    Fabrizia Buongiorno, Maria; Musacchio, Massimo; Guerra, Ignazio; Porco, Giacinto; Stramondo, Salvatore; Casula, Giuseppe; Caserta, Arrigo; Speranza, Fabio; Doumaz, Fawzi; Giovanna Bianchi, Maria; Luzi, Guido; Ilaria Pannaccione Apa, Maria; Montuori, Antonio; Gaudiosi, Iolanda; Vecchio, Antonio; Gervasi, Anna; Bonali, Elena; Romano, Dolores; Falcone, Sergio; La Piana, Carmelo

    2014-05-01

    In the recent years, the concepts of seismic risk vulnerability and structural health monitoring have become very important topics in the field of both structural and civil engineering for the identification of appropriate risk indicators and risk assessment methodologies in Cultural Heritages monitoring. The latter, which includes objects, building and sites with historical, architectural and/or engineering relevance, concerns the management, the preservation and the maintenance of the heritages within their surrounding environmental context, in response to climate changes and natural hazards (e.g. seismic, volcanic, landslides and flooding hazards). Within such a framework, the complexity and the great number of variables to be considered require a multi-disciplinary approach including strategies, methodologies and tools able to provide an effective monitoring of Cultural Heritages form both scientific and operational viewpoints. Based on this rationale, in this study, an advanced, technological and operationally-oriented approach is presented and tested, which enables measuring and monitoring Cultural Heritage conservation state and geophysical/geological setting of the area, in order to mitigate the seismic risk of the historical public goods at different spatial scales*. The integration between classical geophysical methods with new emerging sensing techniques enables a multi-depth, multi-resolution, and multi-scale monitoring in both space and time. An integrated system of methodologies, instrumentation and data-processing approaches for non-destructive Cultural Heritage investigations is proposed, which concerns, in detail, the analysis of seismogenetic sources, the geological-geotechnical setting of the area and site seismic effects evaluation, proximal remote sensing techniques (e.g. terrestrial laser scanner, ground-based radar systems, thermal cameras), high-resolution aerial and satellite-based remote sensing methodologies (e.g. aeromagnetic surveys, synthetic aperture radar, optical, multispectral and panchromatic measurements), static and dynamic structural health monitoring analysis (e.g. screening tests with georadar, sonic instruments, sclerometers and optic fibers). The final purpose of the proposed approach is the development of an investigation methodology for short- and long-term Cultural Heritages preservation in response to seismic stress, which has specific features of scalability, modularity and exportability for every possible monitoring configuration. Moreover, it allows gathering useful information to furnish guidelines for Institution and local Administration to plan consolidation actions and therefore prevention activity. Some preliminary results will be presented for the test site of Calabria Region, where some architectural heritages have been properly selected as case studies for monitoring purposes. *The present work is supported and funded by Ministero dell'Università, dell'Istruzione e della Ricerca (MIUR) under the research project PON01-02710 "MASSIMO" - "Monitoraggio in Area Sismica di Sistemi Monumentali".

  11. A joint swarm intelligence algorithm for multi-user detection in MIMO-OFDM system

    NASA Astrophysics Data System (ADS)

    Hu, Fengye; Du, Dakun; Zhang, Peng; Wang, Zhijun

    2014-11-01

    In the multi-input multi-output orthogonal frequency division multiplexing (MIMO-OFDM) system, traditional multi-user detection (MUD) algorithms that usually used to suppress multiple access interference are difficult to balance system detection performance and the complexity of the algorithm. To solve this problem, this paper proposes a joint swarm intelligence algorithm called Ant Colony and Particle Swarm Optimisation (AC-PSO) by integrating particle swarm optimisation (PSO) and ant colony optimisation (ACO) algorithms. According to simulation results, it has been shown that, with low computational complexity, the MUD for the MIMO-OFDM system based on AC-PSO algorithm gains comparable MUD performance with maximum likelihood algorithm. Thus, the proposed AC-PSO algorithm provides a satisfactory trade-off between computational complexity and detection performance.

  12. Simulating and mapping spatial complexity using multi-scale techniques

    USGS Publications Warehouse

    De Cola, L.

    1994-01-01

    A central problem in spatial analysis is the mapping of data for complex spatial fields using relatively simple data structures, such as those of a conventional GIS. This complexity can be measured using such indices as multi-scale variance, which reflects spatial autocorrelation, and multi-fractal dimension, which characterizes the values of fields. These indices are computed for three spatial processes: Gaussian noise, a simple mathematical function, and data for a random walk. Fractal analysis is then used to produce a vegetation map of the central region of California based on a satellite image. This analysis suggests that real world data lie on a continuum between the simple and the random, and that a major GIS challenge is the scientific representation and understanding of rapidly changing multi-scale fields. -Author

  13. Differences in the phenotypic effects of mutations in homologous MrpA and MrpD subunits of the multi-subunit Mrp-type Na+/H+ antiporter.

    PubMed

    Morino, Masato; Ogoda, Shinichiro; Krulwich, Terry Ann; Ito, Masahiro

    2017-01-01

    Mrp antiporters are the sole antiporters in the Cation/Proton Antiporter 3 family of transporter databases because of their unusual structural complexity, 6-7 hydrophobic proteins that function as a hetero-oligomeric complex. The two largest and homologous subunits, MrpA and MrpD, are essential for antiport activity and have direct roles in ion transport. They also show striking homology with proton-conducting, membrane-embedded Nuo subunits of respiratory chain complex I of bacteria, e.g., Escherichia coli. MrpA has the closest homology to the complex I NuoL subunit and MrpD has the closest homology to the complex I NuoM and N subunits. Here, introduction of mutations in MrpD, in residues that are also present in MrpA, led to defects in antiport function and/or complex formation. No significant phenotypes were detected in strains with mutations in corresponding residues of MrpA, but site-directed changes in the C-terminal region of MrpA had profound effects, showing that the MrpA C-terminal region has indispensable roles in antiport function. The results are consistent with a divergence in adaptations that support the roles of MrpA and MrpD in secondary antiport, as compared to later adaptations supporting homologs in primary proton pumping by the respiratory chain complex I.

  14. CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.

    PubMed

    Zhang, Zijun; Xing, Yi

    2017-09-19

    Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation. CLAM recovered a large number of novel RNA regulatory sites inaccessible by uniquely mapped reads. The functional significance of these sites was demonstrated by consensus motif patterns and association with alternative splicing (splicing factors), transcript abundance (AGO2) and mRNA half-life (m6A). CLAM provides a useful tool to discover novel protein-RNA interactions and RNA modification sites from CLIP-seq and RIP-seq data, and reveals the significant contribution of repetitive elements to the RNA regulatory landscape of the human transcriptome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Childhood Traumatic Grief: A Multi-Site Empirical Examination of the Construct and Its Correlates

    ERIC Educational Resources Information Center

    Brown, Elissa J.; Amaya-Jackson, Lisa; Cohen, Judith; Handel, Stephanie; De Bocanegra, Heike Thiel; Zatta, Eileen; Goodman, Robin F.; Mannarino, Anthony

    2008-01-01

    This study evaluated the construct of childhood traumatic grief (CTG) and its correlates through a multi-site assessment of 132 bereaved children and adolescents. Youth completed a new measure of the characteristics, attributions, and reactions to exposure to death (CARED), as well as measures of CTG, posttraumatic stress disorder (PTSD),…

  16. Collaborative Imaginaries and Multi-Sited Ethnography: Space-Time Dimensions of Engagement in an Afterschool Science Programme for Girls

    ERIC Educational Resources Information Center

    Rahm, Jrene

    2012-01-01

    Temporal and spatial configurations that constitute learning and identity work across practices have been little explored in studies of science literacy development. Grounded in multi-sited ethnography, this paper explores diverse girls' engagement with and identity work in science locally, inside a newsletter activity in an afterschool programme…

  17. Multi-Site Ethnography, Hypermedia and the Productive Hazards of Digital Methods: A Struggle for Liveness

    ERIC Educational Resources Information Center

    Gallagher, Kathleen; Freeman, Barry

    2011-01-01

    This article explores the possibilities and frustrations of using digital methods in a multi-sited ethnographic research project. The project, "Urban School Performances: The interplay, through live and digital drama, of local-global knowledge about student engagement", is a study of youth and teachers in drama classrooms in contexts of…

  18. A Qualitative Multi-Site Case Study: Examining Principals' Leadership Styles and School Performance

    ERIC Educational Resources Information Center

    Preyear, Loukisha

    2015-01-01

    The purpose of this qualitative multi-site case study was to explore the impact of principals' leadership styles on student academic achievement in a high-poverty low-performing school district in Louisiana. A total of 17 participants, principals and teachers, from this school district were used in this study. Data source triangulation of…

  19. Efficient multi-site two-photon functional imaging of neuronal circuits.

    PubMed

    Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R

    2016-12-01

    Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms.

  20. Efficient multi-site two-photon functional imaging of neuronal circuits

    PubMed Central

    Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R.

    2016-01-01

    Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms. PMID:28018745

  1. Allostery Mediates Ligand Binding to Grb2 Adaptor in a Mutually Exclusive Manner

    PubMed Central

    McDonald, Caleb B.; El Hokayem, Jimmy; Zafar, Nawal; Balke, Jordan E.; Bhat, Vikas; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Farooq, Amjad

    2012-01-01

    Allostery plays a key role in dictating the stoichiometry and thermodynamics of multi-protein complexes driving a plethora of cellular processes central to health and disease. Herein, using various biophysical tools, we demonstrate that although Sos1 nucleotide exchange factor and Gab1 docking protein recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2-Sos1 and Grb2-Gab1 binary signaling complexes in concert in lieu of a composite Sos1-Grb2-Gab1 ternary complex. Of particular interest is the observation that the binding of Sos1 to the nSH3 domain within Grb2 sterically blocks the binding of Gab1 to the cSH3 domain and vice versa in a mutually exclusive manner. Importantly, the formation of both the Grb2-Sos1 and Grb2-Gab1 binary complexes is governed by a stoichiometry of 2:1, whereby the respective SH3 domains within Grb2 homodimer bind to Sos1 and Gab1 via multivalent interactions. Collectively, our study sheds new light on the role of allostery in mediating cellular signaling machinery. PMID:23334917

  2. A road map for multi-way calibration models.

    PubMed

    Escandar, Graciela M; Olivieri, Alejandro C

    2017-08-07

    A large number of experimental applications of multi-way calibration are known, and a variety of chemometric models are available for the processing of multi-way data. While the main focus has been directed towards three-way data, due to the availability of various instrumental matrix measurements, a growing number of reports are being produced on order signals of increasing complexity. The purpose of this review is to present a general scheme for selecting the appropriate data processing model, according to the properties exhibited by the multi-way data. In spite of the complexity of the multi-way instrumental measurements, simple criteria can be proposed for model selection, based on the presence and number of the so-called multi-linearity breaking modes (instrumental modes that break the low-rank multi-linearity of the multi-way arrays), and also on the existence of mutually dependent instrumental modes. Recent literature reports on multi-way calibration are reviewed, with emphasis on the models that were selected for data processing.

  3. Validity and feasibility of a satellite imagery-based method for rapid estimation of displaced populations

    PubMed Central

    2013-01-01

    Background Estimating the size of forcibly displaced populations is key to documenting their plight and allocating sufficient resources to their assistance, but is often not done, particularly during the acute phase of displacement, due to methodological challenges and inaccessibility. In this study, we explored the potential use of very high resolution satellite imagery to remotely estimate forcibly displaced populations. Methods Our method consisted of multiplying (i) manual counts of assumed residential structures on a satellite image and (ii) estimates of the mean number of people per structure (structure occupancy) obtained from publicly available reports. We computed population estimates for 11 sites in Bangladesh, Chad, Democratic Republic of Congo, Ethiopia, Haiti, Kenya and Mozambique (six refugee camps, three internally displaced persons’ camps and two urban neighbourhoods with a mixture of residents and displaced) ranging in population from 1,969 to 90,547, and compared these to “gold standard” reference population figures from census or other robust methods. Results Structure counts by independent analysts were reasonably consistent. Between one and 11 occupancy reports were available per site and most of these reported people per household rather than per structure. The imagery-based method had a precision relative to reference population figures of <10% in four sites and 10–30% in three sites, but severely over-estimated the population in an Ethiopian camp with implausible occupancy data and two post-earthquake Haiti sites featuring dense and complex residential layout. For each site, estimates were produced in 2–5 working person-days. Conclusions In settings with clearly distinguishable individual structures, the remote, imagery-based method had reasonable accuracy for the purposes of rapid estimation, was simple and quick to implement, and would likely perform better in more current application. However, it may have insurmountable limitations in settings featuring connected buildings or shelters, a complex pattern of roofs and multi-level buildings. Based on these results, we discuss possible ways forward for the method’s development. PMID:23343099

  4. Validity and feasibility of a satellite imagery-based method for rapid estimation of displaced populations.

    PubMed

    Checchi, Francesco; Stewart, Barclay T; Palmer, Jennifer J; Grundy, Chris

    2013-01-23

    Estimating the size of forcibly displaced populations is key to documenting their plight and allocating sufficient resources to their assistance, but is often not done, particularly during the acute phase of displacement, due to methodological challenges and inaccessibility. In this study, we explored the potential use of very high resolution satellite imagery to remotely estimate forcibly displaced populations. Our method consisted of multiplying (i) manual counts of assumed residential structures on a satellite image and (ii) estimates of the mean number of people per structure (structure occupancy) obtained from publicly available reports. We computed population estimates for 11 sites in Bangladesh, Chad, Democratic Republic of Congo, Ethiopia, Haiti, Kenya and Mozambique (six refugee camps, three internally displaced persons' camps and two urban neighbourhoods with a mixture of residents and displaced) ranging in population from 1,969 to 90,547, and compared these to "gold standard" reference population figures from census or other robust methods. Structure counts by independent analysts were reasonably consistent. Between one and 11 occupancy reports were available per site and most of these reported people per household rather than per structure. The imagery-based method had a precision relative to reference population figures of <10% in four sites and 10-30% in three sites, but severely over-estimated the population in an Ethiopian camp with implausible occupancy data and two post-earthquake Haiti sites featuring dense and complex residential layout. For each site, estimates were produced in 2-5 working person-days. In settings with clearly distinguishable individual structures, the remote, imagery-based method had reasonable accuracy for the purposes of rapid estimation, was simple and quick to implement, and would likely perform better in more current application. However, it may have insurmountable limitations in settings featuring connected buildings or shelters, a complex pattern of roofs and multi-level buildings. Based on these results, we discuss possible ways forward for the method's development.

  5. The multi-replication protein A (RPA) system--a new perspective.

    PubMed

    Sakaguchi, Kengo; Ishibashi, Toyotaka; Uchiyama, Yukinobu; Iwabata, Kazuki

    2009-02-01

    Replication protein A (RPA) complex has been shown, using both in vivo and in vitro approaches, to be required for most aspects of eukaryotic DNA metabolism: replication, repair, telomere maintenance and homologous recombination. Here, we review recent data concerning the function and biological importance of the multi-RPA complex. There are distinct complexes of RPA found in the biological kingdoms, although for a long time only one type of RPA complex was believed to be present in eukaryotes. Each complex probably serves a different role. In higher plants, three distinct large and medium subunits are present, but only one species of the smallest subunit. Each of these protein subunits forms stable complexes with their respective partners. They are paralogs as complex. Humans possess two paralogs and one analog of RPA. The multi-RPA system can be regarded as universal in eukaryotes. Among eukaryotic kingdoms, paralogs, orthologs, analogs and heterologs of many DNA synthesis-related factors, including RPA, are ubiquitous. Convergent evolution seems to be ubiquitous in these processes. Using recent findings, we review the composition and biological functions of RPA complexes.

  6. Vertically-integrated Approaches for Carbon Sequestration Modeling

    NASA Astrophysics Data System (ADS)

    Bandilla, K.; Celia, M. A.; Guo, B.

    2015-12-01

    Carbon capture and sequestration (CCS) is being considered as an approach to mitigate anthropogenic CO2 emissions from large stationary sources such as coal fired power plants and natural gas processing plants. Computer modeling is an essential tool for site design and operational planning as it allows prediction of the pressure response as well as the migration of both CO2 and brine in the subsurface. Many processes, such as buoyancy, hysteresis, geomechanics and geochemistry, can have important impacts on the system. While all of the processes can be taken into account simultaneously, the resulting models are computationally very expensive and require large numbers of parameters which are often uncertain or unknown. In many cases of practical interest, the computational and data requirements can be reduced by choosing a smaller domain and/or by neglecting or simplifying certain processes. This leads to a series of models with different complexity, ranging from coupled multi-physics, multi-phase three-dimensional models to semi-analytical single-phase models. Under certain conditions the three-dimensional equations can be integrated in the vertical direction, leading to a suite of two-dimensional multi-phase models, termed vertically-integrated models. These models are either solved numerically or simplified further (e.g., assumption of vertical equilibrium) to allow analytical or semi-analytical solutions. This presentation focuses on how different vertically-integrated models have been applied to the simulation of CO2 and brine migration during CCS projects. Several example sites, such as the Illinois Basin and the Wabamun Lake region of the Alberta Basin, are discussed to show how vertically-integrated models can be used to gain understanding of CCS operations.

  7. Data quality assessment for comparative effectiveness research in distributed data networks

    PubMed Central

    Brown, Jeffrey; Kahn, Michael; Toh, Sengwee

    2015-01-01

    Background Electronic health information routinely collected during healthcare delivery and reimbursement can help address the need for evidence about the real-world effectiveness, safety, and quality of medical care. Often, distributed networks that combine information from multiple sources are needed to generate this real-world evidence. Objective We provide a set of field-tested best practices and a set of recommendations for data quality checking for comparative effectiveness research (CER) in distributed data networks. Methods Explore the requirements for data quality checking and describe data quality approaches undertaken by several existing multi-site networks. Results There are no established standards regarding how to evaluate the quality of electronic health data for CER within distributed networks. Data checks of increasing complexity are often employed, ranging from consistency with syntactic rules to evaluation of semantics and consistency within and across sites. Temporal trends within and across sites are widely used, as are checks of each data refresh or update. Rates of specific events and exposures by age group, sex, and month are also common. Discussion Secondary use of electronic health data for CER holds promise but is complex, especially in distributed data networks that incorporate periodic data refreshes. The viability of a learning health system is dependent on a robust understanding of the quality, validity, and optimal secondary uses of routinely collected electronic health data within distributed health data networks. Robust data quality checking can strengthen confidence in findings based on distributed data network. PMID:23793049

  8. Transcriptome analysis reveals the complexity of alternative splicing regulation in the fungus Verticillium dahliae.

    PubMed

    Jin, Lirong; Li, Guanglin; Yu, Dazhao; Huang, Wei; Cheng, Chao; Liao, Shengjie; Wu, Qijia; Zhang, Yi

    2017-02-06

    Alternative splicing (AS) regulation is extensive and shapes the functional complexity of higher organisms. However, the contribution of alternative splicing to fungal biology is not well studied. This study provides sequences of the transcriptomes of the plant wilt pathogen Verticillium dahliae, using two different strains and multiple methods for cDNA library preparations. We identified alternatively spliced mRNA isoforms in over a half of the multi-exonic fungal genes. Over one-thousand isoforms involve TopHat novel splice junction; multiple types of combinatory alternative splicing patterns were identified. We showed that one Verticillium gene could use four different 5' splice sites and two different 3' donor sites to produce up to five mature mRNAs, representing one of the most sophisticated alternative splicing model in eukaryotes other than animals. Hundreds of novel intron types involving a pair of new splice sites were identified in the V. dahliae genome. All the types of AS events were validated by using RT-PCR. Functional enrichment analysis showed that AS genes are involved in most known biological functions and enriched in ATP biosynthesis, sexual/asexual reproduction, morphogenesis, signal transduction etc., predicting that the AS regulation modulates mRNA isoform output and shapes the V. dahliae proteome plasticity of the pathogen in response to the environmental and developmental changes. These findings demonstrate the comprehensive alternative splicing mechanisms in a fungal plant pathogen, which argues the importance of this fungus in developing complicate genome regulation strategies in eukaryotes.

  9. Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

    PubMed Central

    Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

    2011-01-01

    Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

  10. MULTI-MEDIA MODELING : RESEARCH AND DEVELOPMENT

    EPA Science Inventory

    Developed by ORD in collaboration with OSW, the Multimedia, Multi-pathway, Multi-receptor Risk Assessment (3MRA) national risk assessment methodology is designed to assess risks at sites containing source(s) of contamination that may release contaminants to the environment. Or...

  11. Adsorption of selenium by amorphous iron oxyhydroxide and manganese dioxide

    USGS Publications Warehouse

    Balistrieri, L.S.; Chao, T.T.

    1990-01-01

    This work compares and models the adsorption of selenium and other anions on a neutral to alkaline surface (amorphous iron oxyhydroxide) and an acidic surface (manganese dioxide). Selenium adsorption on these oxides is examined as a function of pH, particle concentration, oxidation state, and competing anion concentration in order to assess how these factors might influence the mobility of selenium in the environment. The data indicate that 1. 1) amorphous iron oxyhydroxide has a greater affinity for selenium than manganese dioxide, 2. 2) selenite [Se(IV)] adsorption increases with decreasing pH and increasing particle concentration and is stronger than selenate [Se(VI)] adsorption on both oxides, and 3. 3) selenate does not adsorb on manganese dioxide. The relative affinity of selenate and selenite for the oxides and the lack of adsorption of selenate on a strongly acidic surface suggests that selenate forms outer-sphere complexes while selenite forms inner-sphere complexes with the surfaces. The data also indicate that the competition sequence of other anions with respect to selenite adsorption at pH 7.0 is phosphate > silicate > molybdate > fluoride > sulfate on amorphous iron oxyhydroxide and molybdate ??? phosphate > silicate > fluoride > sulfate on manganese dioxide. The adsorption of phosphate, molybdate, and silicate on these oxides as a function of pH indicates that the competition sequences reflect the relative affinities of these anions for the surfaces. The Triple Layer surface complexation model is used to provide a quantitative description of these observations and to assess the importance of surface site heterogeneity on anion adsorption. The modeling results suggest that selenite forms binuclear, innersphere complexes with amorphous iron oxyhydroxide and monodentate, inner-sphere complexes with manganese dioxide and that selenate forms outer-sphere, monodentate complexes with amorphous iron oxyhydroxide. The heterogeneity of the oxide surface sites is reflected in decreasing equilibrium constants for selenite with increasing adsorption density and both experimental observations and modeling results suggest that manganese dioxide has fewer sites of higher energy for selenite adsorption than amorphous iron oxyhydroxide. Modeling and interpreting the adsorption of phosphate, molybdate, and silicate on the oxides are made difficult by the lack of constraint in choosing surface species and the fact that equally good fits can be obtained with different surface species. Finally, predictions of anion competition using the model results from single adsorbate systems are not very successful because the model does not account for surface site heterogeneity. Selenite adsorption data from a multi-adsorbate system could be fit if the equilibrium constant for selenite is decreased with increasing anion adsorption density. ?? 1990.

  12. Multi-focal multiphoton lithography.

    PubMed

    Ritschdorff, Eric T; Nielson, Rex; Shear, Jason B

    2012-03-07

    Multiphoton lithography (MPL) provides unparalleled capabilities for creating high-resolution, three-dimensional (3D) materials from a broad spectrum of building blocks and with few limitations on geometry, qualities that have been key to the design of chemically, mechanically, and biologically functional microforms. Unfortunately, the reliance of MPL on laser scanning limits the speed at which fabrication can be performed, making it impractical in many instances to produce large-scale, high-resolution objects such as complex micromachines, 3D microfluidics, etc. Previously, others have demonstrated the possibility of using multiple laser foci to simultaneously perform MPL at numerous sites in parallel, but use of a stage-scanning system to specify fabrication coordinates resulted in the production of identical features at each focal position. As a more general solution to the bottleneck problem, we demonstrate here the feasibility for performing multi-focal MPL using a dynamic mask to differentially modulate foci, an approach that enables each fabrication site to create independent (uncorrelated) features within a larger, integrated microform. In this proof-of-concept study, two simultaneously scanned foci produced the expected two-fold decrease in fabrication time, and this approach could be readily extended to many scanning foci by using a more powerful laser. Finally, we show that use of multiple foci in MPL can be exploited to assign heterogeneous properties (such as differential swelling) to micromaterials at distinct positions within a fabrication zone.

  13. Simplifying the Analysis of Data from Multiple Heliophysics Instruments and Missions

    NASA Astrophysics Data System (ADS)

    Bazell, D.; Vandegriff, J. D.

    2014-12-01

    Understanding the intertwined plasma, particles and fields connecting the Sun and the Earth requires combining data from many diverse sources, but there are still many technological barriers that complicate the merging of data from different instruments and missions. We present an emerging data serving capability that provides a uniform way to access heterogeneous and distributed data. The goal of our data server is to provide a standardized data access mechanism that is identical for data of any format and layout (CDF, custom binary, FITS, netCDF, CSV and other flavors of ASCII, etc). Data remain in their original format and location (i.e., at instrument team sites or existing data centers), and our data server delivers a dynamically reformatted view of the data. Scientists can then use tools (clients that talk to the server) that offer a single interface for browsing, analyzing or downloading many different contemporary and legacy heliophysics data sets. Our current server accesses many CDF data resources at CDAWeb, as well as multiple other instrument team sites. Our webservice will be deployed on the Amazon Cloud at http://datashop.elasticbeanstalk.com/. Two basic clients will also be demonstrated: one in Java and one in IDL. Python, Perl, and Matlab clients are also planned. Complex missions such as Solar Orbiter and Solar Probe Plus will benefit greatly from tools that enable multi-instrument and multi-mission data comparison.

  14. Artificial light-regulation of an allosteric bi-enzyme complex by a photosensitive ligand.

    PubMed

    Kneuttinger, Andrea C; Winter, Martin; Simeth, Nadja A; Heyn, Kristina; Merkl, Rainer; König, Burkhard; Sterner, Reinhard

    2018-05-29

    The artificial regulation of proteins by light is an emerging sub-discipline of synthetic biology. Here, we used this concept in order to photo-control both catalysis and allostery within the heterodimeric enzyme complex imidazole glycerol phosphate synthase (ImGP-S). The ImGP-S consists of the cyclase subunit HisF and the glutaminase subunit HisH, which is allosterically stimulated by substrate binding to HisF. We show that a light-sensitive diarylethene (DTE)-based competitive inhibitor in its ring-open state binds with low micromolar affinity to the cyclase subunit and displaces its substrate from the active site. As a consequence, catalysis by HisF and allosteric stimulation of HisH are impaired. Following UV-light irradiation, the DTE-ligand adopts its ring-closed state and loses affinity for HisF, restoring activity and allostery. Our approach allows for the switching of ImGP-S activity and allostery during catalysis and appears to be generally applicable for the light-regulation of other multi-enzyme complexes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Arsenic Re-Mobilization in Water Treatment Adsorbents Under Reducing Conditions: Part II, XAS and Modeling Study

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

    Liu,S.; Jing, C.; Meng, X.

    2008-01-01

    The mechanism of arsenic re-mobilization in spent adsorbents under reducing conditions was studied using X-ray absorption spectroscopy and surface complexation model calculations. X-ray absorption near edge structure (XANES) spectroscopy demonstrated that As(V) was partially reduced to As(III) in spent granular ferric hydroxide (GFH), titanium dioxide (TiO2), activated alumina (AA) and modified activated alumina (MAA) adsorbents after 2 years of anaerobic incubation. As(V) was completely reduced to As(III) in spent granular ferric oxide (GFO) under 2-year incubation. The extended X-ray absorption fine structure (EXAFS) spectroscopy analysis showed that As(III) formed bidentate binuclear surface complexes on GFO as evidenced by an averagemore » As(III)-O bond distance of 1.78 Angstroms and As(III)-Fe distance of 3.34 Angstroms . The release of As from the spent GFO and TiO2 was simulated using the charge distribution multi-site complexation (CD-MUSIC) model. The observed redox ranges for As release and sulfate mobility were described by model calculations.« less

  16. Multisite adsorption of cadmium on goethite

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

    Venema, P.; Hiemstra, T.; Riemsdijk, W.H. van

    1996-11-10

    Recently a new general ion adsorption model has been developed for ion binding to mineral surfaces (Hiemstra and van Riemsdijk, 1996). The model uses the Pauling concept of charge distribution (CD) and is an extension of the multi-site complexation (MUSIC) approach. In the CD-MUSIC model the charge of an adsorbing ion that forms an inner sphere complex is distributed over its ligands, which are present in two different electrostatic planes. In this paper the authors have applied the CD-MUSIC model to the adsorption of metal cations, using an extended data set for cadmium adsorbing on goethite. The adsorption of cadmiummore » and the cadmium-proton exchange ratio were measured as function of metal ion concentration, pH, and ionic strength. The data could be described well, taking into account the surface heterogeneity resulting from the presence of two different crystal planes (the dominant 110 face and the minor 021 face). The surface species used in the model are consistent with recent EXAFS data. In accordance with the EXAFS results, high-affinity complexes at the 021 face were used in the model.« less

  17. The BioIntelligence Framework: a new computational platform for biomedical knowledge computing.

    PubMed

    Farley, Toni; Kiefer, Jeff; Lee, Preston; Von Hoff, Daniel; Trent, Jeffrey M; Colbourn, Charles; Mousses, Spyro

    2013-01-01

    Breakthroughs in molecular profiling technologies are enabling a new data-intensive approach to biomedical research, with the potential to revolutionize how we study, manage, and treat complex diseases. The next great challenge for clinical applications of these innovations will be to create scalable computational solutions for intelligently linking complex biomedical patient data to clinically actionable knowledge. Traditional database management systems (DBMS) are not well suited to representing complex syntactic and semantic relationships in unstructured biomedical information, introducing barriers to realizing such solutions. We propose a scalable computational framework for addressing this need, which leverages a hypergraph-based data model and query language that may be better suited for representing complex multi-lateral, multi-scalar, and multi-dimensional relationships. We also discuss how this framework can be used to create rapid learning knowledge base systems to intelligently capture and relate complex patient data to biomedical knowledge in order to automate the recovery of clinically actionable information.

  18. A Suite of Tetraphenylethylene-Based Discrete Organoplatinum(II) Metallacycles: Controllable Structure and Stoichiometry, Aggregation-Induced Emission, and Nitroaromatics Sensing.

    PubMed

    Yan, Xuzhou; Wang, Haoze; Hauke, Cory E; Cook, Timothy R; Wang, Ming; Saha, Manik Lal; Zhou, Zhixuan; Zhang, Mingming; Li, Xiaopeng; Huang, Feihe; Stang, Peter J

    2015-12-09

    Materials that organize multiple functionally active sites, especially those with aggregation-induced emission (AIE) properties, are of growing interest due to their widespread applications. Despite promising early architectures, the fabrication and preparation of multiple AIEgens, such as multiple tetraphenylethylene (multi-TPE) units, in a single entity remain a big challenge due to the tedious covalent synthetic procedures often accompanying such preparations. Coordination-driven self-assembly is an alternative synthetic methodology with the potential to deliver multi-TPE architectures with light-emitting characteristics. Herein, we report the preparation of a new family of discrete multi-TPE metallacycles in which two pendant phenyl rings of the TPE units remain unused as a structural element, representing novel AIE-active metal-organic materials based on supramolecular coordination complex platforms. These metallacycles possess relatively high molar absorption coefficients but weak fluorescent emission under dilute conditions because of the ability of the untethered phenyl rings to undergo torsional motion as a non-radiative decay pathway. Upon molecular aggregation, the multi-TPE metallacycles show AIE-activity with markedly enhanced quantum yields. Moreover, on account of their AIE characteristics in the condensed state and ability to interact with electron-deficient substrates, the photophysics of these metallacycles is sensitive to the presence of nitroaromatics, motivating their use as sensors. This work represents a unification of themes including molecular self-assembly, AIE, and fluorescence sensing and establishes structure-property-application relationships of multi-TPE scaffolds. The fundamental knowledge obtained from the current research facilitates progress in the field of metal-organic materials, metal-coordination-induced emission, and fluorescent sensing.

  19. In situ impact assessment of wastewater effluents by integrating multi-level biomarker responses in the pale chub (Zacco platypus).

    PubMed

    Kim, Woo-Keun; Jung, Jinho

    2016-06-01

    The integration of biomarker responses ranging from the molecular to the individual level is of great interest for measuring the toxic effects of hazardous chemicals or effluent mixtures on aquatic organisms. This study evaluated the effects of wastewater treatment plant (WWTP) effluents on the freshwater pale chub Zacco platypus by using multi-level biomarker responses at molecular [mRNA expression of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and metallothionein (MT)], biochemical (enzyme activities of CAT, SOD, GST, and concentration of MT), and physiological [condition factor (CF) and liver somatic index (LSI)] levels. The mRNA expression levels of GST and MT in Z. platypus from a site downstream of a WWTP significantly increased by 2.2- and 4.5-fold (p<0.05) when compared with those from an upstream site. However, the enzyme activities of CAT, SOD, and GST in fish from the downstream site significantly decreased by 43%, 98%, and 13%, respectively (p<0.05), except for an increase in MT concentration (41%). In addition, a significant increase in LSI (46%) was observed in Z. platypus from the downstream site (p<0.05). Concentrations of Cu, Zn, Cd, and Pb in the liver of Z. platypus were higher (530%, 353%, 800%, and 2,200%, respectively) in fish from a downstream site than in fish from an upstream location, and several multi-level biomarker responses were significantly correlated with the accumulated metals in Z. platypus (p<0.05). Integrated biomarker responses at molecular, biochemical, and physiological levels (multi-level IBR) were much higher (about 4-fold) at the downstream site than at the upstream site. This study suggests that the multi-level IBR approach is very useful for quantifying in situ adverse effects of WWTP effluents. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Multi-complexity ensemble measures for gait time series analysis: application to diagnostics, monitoring and biometrics.

    PubMed

    Gavrishchaka, Valeriy; Senyukova, Olga; Davis, Kristina

    2015-01-01

    Previously, we have proposed to use complementary complexity measures discovered by boosting-like ensemble learning for the enhancement of quantitative indicators dealing with necessarily short physiological time series. We have confirmed robustness of such multi-complexity measures for heart rate variability analysis with the emphasis on detection of emerging and intermittent cardiac abnormalities. Recently, we presented preliminary results suggesting that such ensemble-based approach could be also effective in discovering universal meta-indicators for early detection and convenient monitoring of neurological abnormalities using gait time series. Here, we argue and demonstrate that these multi-complexity ensemble measures for gait time series analysis could have significantly wider application scope ranging from diagnostics and early detection of physiological regime change to gait-based biometrics applications.

  1. Multi-frequency complex network from time series for uncovering oil-water flow structure.

    PubMed

    Gao, Zhong-Ke; Yang, Yu-Xuan; Fang, Peng-Cheng; Jin, Ning-De; Xia, Cheng-Yi; Hu, Li-Dan

    2015-02-04

    Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective.

  2. Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.

    PubMed

    Mazor, Roei D; Manevich-Mazor, Mirra; Kesler, Anat; Aizenstein, Orna; Eshed, Iris; Jaffe, Ronald; Pessach, Yakov; Goldberg, Ilan; Sprecher, Eli; Yaish, Iris; Gural, Alexander; Ganzel, Chezi; Shoenfeld, Yehuda

    2014-12-01

    Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

  3. The Control Based on Internal Average Kinetic Energy in Complex Environment for Multi-robot System

    NASA Astrophysics Data System (ADS)

    Yang, Mao; Tian, Yantao; Yin, Xianghua

    In this paper, reference trajectory is designed according to minimum energy consumed for multi-robot system, which nonlinear programming and cubic spline interpolation are adopted. The control strategy is composed of two levels, which lower-level is simple PD control and the upper-level is based on the internal average kinetic energy for multi-robot system in the complex environment with velocity damping. Simulation tests verify the effectiveness of this control strategy.

  4. Determination of optimum "multi-channel surface wave method" field parameters.

    DOT National Transportation Integrated Search

    2012-12-01

    Multi-channel surface wave methods (especially the multi-channel analyses of surface wave method; MASW) are routinely used to : determine the shear-wave velocity of the subsurface to depths of 100 feet for site classification purposes. Users are awar...

  5. Awareness of Diagnosis and Knowledge of HPV in Women Patients: Data from a Multi-Site Study

    ERIC Educational Resources Information Center

    McCree, Donna Hubbard; Daley, Ellen M.; Gorbach, Pamina; Hamm, Robert M.; Sharpe, Patricia A.; Brandt, Heather M.; McFarlane, Mary; Kerndt, Peter; McDermott, Robert J.; Perrin, Karen M.; St. Lawrence, Janet S.

    2010-01-01

    Background: Persistent infection with high-risk types of human papillomavirus (HPV) is associated with cervical and other anogenital cancers. Purpose: This paper reports results of awareness of an HPV diagnosis and HPV knowledge from a multi-site study of HPV knowledge, attitudes and behavior, and the impact of an HPV diagnosis on women and their…

  6. An Examination of Diversity within Three Southeastern Academic Libraries: A Mixed-Methods, Multi-Site Study

    ERIC Educational Resources Information Center

    Shaffer, Christopher A.

    2014-01-01

    The purpose of this study was to determine the extent to which three academic libraries in the Southeastern United States could be considered diverse. This was a multi-site, mixed methods study. It examined the climate and culture of the libraries, which was assessed through two methods; the first, through survey responses from full-time faculty…

  7. The Setting-up of Multi-Site School Collaboratives: The Benefits of This Organizational Reform in Terms of Networking Opportunities and Their Effects

    ERIC Educational Resources Information Center

    Mifsud, Denise

    2015-01-01

    This article, which is set within the Maltese education scenario of unfolding decentralization through the setting-up of multi-site school collaboratives (legally termed "colleges") via a policy mandate, explores a particular aspect of this reform--that of "networking". This is examined in terms of the potential for…

  8. Bias and Bias Correction in Multi-Site Instrumental Variables Analysis of Heterogeneous Mediator Effects

    ERIC Educational Resources Information Center

    Reardon, Sean F.; Unlu, Faith; Zhu, Pei; Bloom, Howard

    2013-01-01

    We explore the use of instrumental variables (IV) analysis with a multi-site randomized trial to estimate the effect of a mediating variable on an outcome in cases where it can be assumed that the observed mediator is the only mechanism linking treatment assignment to outcomes, as assumption known in the instrumental variables literature as the…

  9. Replication and Comparison of the Newly Proposed ADOS-2, Module 4 Algorithm in ASD without ID: A Multi-Site Study

    ERIC Educational Resources Information Center

    Pugliese, Cara E.; Kenworthy, Lauren; Bal, Vanessa Hus; Wallace, Gregory L.; Yerys, Benjamin E.; Maddox, Brenna B.; White, Susan W.; Popal, Haroon; Armour, Anna Chelsea; Miller, Judith; Herrington, John D.; Schultz, Robert T.; Martin, Alex; Anthony, Laura Gutermuth

    2015-01-01

    Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised…

  10. Sensitivity of the Modified Children's Yale-Brown Obsessive Compulsive Scale to Detect Change: Results from Two Multi-Site Trials

    ERIC Educational Resources Information Center

    Scahill, Lawrence; Sukhodolsky, Denis G.; Anderberg, Emily; Dimitropoulos, Anastasia; Dziura, James; Aman, Michael G.; McCracken, James; Tierney, Elaine; Hallett, Victoria; Katz, Karol; Vitiello, Benedetto; McDougle, Christopher

    2016-01-01

    Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism…

  11. SpaceX Falcon Heavy Demo Flight Launch - Press Site

    NASA Image and Video Library

    2018-02-06

    The parking area at the NASA News Center is filled with media vehicles and guest buses in anticipation of the liftoff of the SpaceX Falcon Heavy rocket from Launch Complex 39A at Kennedy Space Center in Florida. The demonstration flight will be a significant milestone for the world's premier multi-user spaceport. In 2014, NASA signed a property agreement with SpaceX for the use and operation of the center's pad 39A, where the company has launched Falcon 9 rockets and is preparing for the first Falcon Heavy. NASA also has Space Act Agreements in place with partners, such as SpaceX, to provide services needed to process and launch rockets and spacecraft.

  12. SpaceX Falcon Heavy Demo Flight - Press Site Activities

    NASA Image and Video Library

    2018-02-06

    Members of the news media begin to gather near the countdown clock at NASA’s Kennedy Space Center in Florida to await liftoff of the SpaceX Falcon Heavy rocket, seen in the background at Launch Complex 39A. The demonstration flight will be a significant milestone for the world's premier multi-user spaceport. In 2014, NASA signed a property agreement with SpaceX for the use and operation of the center's pad 39A, where the company has launched Falcon 9 rockets and is preparing for the first Falcon Heavy. NASA also has Space Act Agreements in place with partners, such as SpaceX, to provide services needed to process and launch rockets and spacecraft.

  13. Grain-Size Based Additivity Models for Scaling Multi-rate Uranyl Surface Complexation in Subsurface Sediments

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

    Zhang, Xiaoying; Liu, Chongxuan; Hu, Bill X.

    The additivity model assumed that field-scale reaction properties in a sediment including surface area, reactive site concentration, and reaction rate can be predicted from field-scale grain-size distribution by linearly adding reaction properties estimated in laboratory for individual grain-size fractions. This study evaluated the additivity model in scaling mass transfer-limited, multi-rate uranyl (U(VI)) surface complexation reactions in a contaminated sediment. Experimental data of rate-limited U(VI) desorption in a stirred flow-cell reactor were used to estimate the statistical properties of the rate constants for individual grain-size fractions, which were then used to predict rate-limited U(VI) desorption in the composite sediment. The resultmore » indicated that the additivity model with respect to the rate of U(VI) desorption provided a good prediction of U(VI) desorption in the composite sediment. However, the rate constants were not directly scalable using the additivity model. An approximate additivity model for directly scaling rate constants was subsequently proposed and evaluated. The result found that the approximate model provided a good prediction of the experimental results within statistical uncertainty. This study also found that a gravel-size fraction (2 to 8 mm), which is often ignored in modeling U(VI) sorption and desorption, is statistically significant to the U(VI) desorption in the sediment.« less

  14. On Using Meta-Modeling and Multi-Modeling to Address Complex Problems

    ERIC Educational Resources Information Center

    Abu Jbara, Ahmed

    2013-01-01

    Models, created using different modeling techniques, usually serve different purposes and provide unique insights. While each modeling technique might be capable of answering specific questions, complex problems require multiple models interoperating to complement/supplement each other; we call this Multi-Modeling. To address the syntactic and…

  15. Tutoring and Multi-Agent Systems: Modeling from Experiences

    ERIC Educational Resources Information Center

    Bennane, Abdellah

    2010-01-01

    Tutoring systems become complex and are offering varieties of pedagogical software as course modules, exercises, simulators, systems online or offline, for single user or multi-user. This complexity motivates new forms and approaches to the design and the modelling. Studies and research in this field introduce emergent concepts that allow the…

  16. Modeling the spatio-temporal variability in subsurface thermal regimes across a low-relief polygonal tundra landscape: Modeling Archive

    DOE Data Explorer

    Kumar, Jitendra; Collier, Nathan; Bisht, Gautam; Mills, Richard T.; Thornton, Peter E.; Iversen, Colleen M.; Romanovsky, Vladimir

    2016-01-27

    This Modeling Archive is in support of an NGEE Arctic discussion paper under review and available at http://www.the-cryosphere-discuss.net/tc-2016-29/. Vast carbon stocks stored in permafrost soils of Arctic tundra are under risk of release to atmosphere under warming climate. Ice--wedge polygons in the low-gradient polygonal tundra create a complex mosaic of microtopographic features. The microtopography plays a critical role in regulating the fine scale variability in thermal and hydrological regimes in the polygonal tundra landscape underlain by continuous permafrost. Modeling of thermal regimes of this sensitive ecosystem is essential for understanding the landscape behaviour under current as well as changing climate. We present here an end-to-end effort for high resolution numerical modeling of thermal hydrology at real-world field sites, utilizing the best available data to characterize and parameterize the models. We develop approaches to model the thermal hydrology of polygonal tundra and apply them at four study sites at Barrow, Alaska spanning across low to transitional to high-centered polygon and representative of broad polygonal tundra landscape. A multi--phase subsurface thermal hydrology model (PFLOTRAN) was developed and applied to study the thermal regimes at four sites. Using high resolution LiDAR DEM, microtopographic features of the landscape were characterized and represented in the high resolution model mesh. Best available soil data from field observations and literature was utilized to represent the complex hetogeneous subsurface in the numerical model. This data collection provides the complete set of input files, forcing data sets and computational meshes for simulations using PFLOTRAN for four sites at Barrow Environmental Observatory. It also document the complete computational workflow for this modeling study to allow verification, reproducibility and follow up studies.

  17. Role of individual phosphorylation sites in inactivation of pyruvate dehydrogenase complex in rat heart mitochondria

    PubMed Central

    Sale, Graham J.; Randle, Philip J.

    1982-01-01

    1. A method is described using trypsin/formic acid cleavage for unambiguously measuring occupancies of phosphorylation sites in rat heart pyruvate dehydrogenase [32P]phosphate complexes. 2. In mitochondria oxidizing 2-oxoglutarate+l-malate relative initial rates of phosphorylation were site 1>site 2>site 3. 3. Dephosphorylation and reactivation of fully phosphorylated complex was initiated in mitochondria by inhibiting the kinase reaction. Using dichloroacetate relative rates of dephosphorylation were site 2>(1=3). Using sodium dithionite or sodium pyruvate or uncouplers+sodium arsenite or steady state turnover (31P replacing 32P in inactive complex) relative rates were site 2>site 1>site 3. With dithionite reactivation was faster than site 3 dephosphorylation, i.e. site 3 is apparently not inactivating. 4. The steady state proportion of inactive complex was varied (92–48%) in mitochondria oxidizing 2-oxoglutarate/l-malate by increasing extramitochondrial Ca2+ (0–2.6μm). This action of Ca2+ induced dephosphorylation (site 3>site 2>site 1). These experiments enable prediction of site occupancies in vivo for given steady state proportions of inactive complexes. 5. The proportion of inactive complex was related linearly to occupancy of site 1. 6. Sodium dithionite (10mm) and Ca2+ (0.5μm) together resulted in faster dephosphorylations of each site than either agent alone; relative rates were site 2>(1=3). 7. Dephosphorylation and possibly phosphorylation of sites 1 and 2 was not purely sequential as shown by detection of complexes phosphorylated in site 2 but not in site 1. Estimates of the contribution of site 2 phosphorylation to inactivation ranged from 0.7 to 6.4%. 8. It is concluded that the primary function of site 1 phosphorylation is inactivation, phosphorylation of site 2 is not primarily concerned with inactivation and that phosphorylation of site 3 is non-inactivating. PMID:7103952

  18. Multi-Objective Algorithm for Blood Supply via Unmanned Aerial Vehicles to the Wounded in an Emergency Situation

    PubMed Central

    Wen, Tingxi; Zhang, Zhongnan; Wong, Kelvin K. L.

    2016-01-01

    Unmanned aerial vehicle (UAV) has been widely used in many industries. In the medical environment, especially in some emergency situations, UAVs play an important role such as the supply of medicines and blood with speed and efficiency. In this paper, we study the problem of multi-objective blood supply by UAVs in such emergency situations. This is a complex problem that includes maintenance of the supply blood’s temperature model during transportation, the UAVs’ scheduling and routes’ planning in case of multiple sites requesting blood, and limited carrying capacity. Most importantly, we need to study the blood’s temperature change due to the external environment, the heating agent (or refrigerant) and time factor during transportation, and propose an optimal method for calculating the mixing proportion of blood and appendage in different circumstances and delivery conditions. Then, by introducing the idea of transportation appendage into the traditional Capacitated Vehicle Routing Problem (CVRP), this new problem is proposed according to the factors of distance and weight. Algorithmically, we use the combination of decomposition-based multi-objective evolutionary algorithm and local search method to perform a series of experiments on the CVRP public dataset. By comparing our technique with the traditional ones, our algorithm can obtain better optimization results and time performance. PMID:27163361

  19. Function Biomedical Informatics Research Network Recommendations for Prospective Multi-Center Functional Magnetic Resonance Imaging Studies

    PubMed Central

    Glover, Gary H.; Mueller, Bryon A.; Turner, Jessica A.; van Erp, Theo G.M.; Liu, Thomas T.; Greve, Douglas N.; Voyvodic, James T.; Rasmussen, Jerod; Brown, Gregory G.; Keator, David B.; Calhoun, Vince D.; Lee, Hyo Jong; Ford, Judith M.; Mathalon, Daniel H.; Diaz, Michele; O’Leary, Daniel S.; Gadde, Syam; Preda, Adrian; Lim, Kelvin O.; Wible, Cynthia G.; Stern, Hal S.; Belger, Aysenil; McCarthy, Gregory; Ozyurt, Burak; Potkin, Steven G.

    2011-01-01

    This report provides practical recommendations for the design and execution of Multi-Center functional Magnetic Resonance Imaging (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The paper was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multi-site aspects include: (1) establishing and verifying scan parameters including scanner types and magnetic fields, (2) establishing and monitoring of a scanner quality program, (3) developing task paradigms and scan session documentation, (4) establishing clinical and scanner training to ensure consistency over time, (5) developing means for uploading, storing, and monitoring of imaging and other data, (6) the use of a traveling fMRI expert and (7) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery. PMID:22314879

  20. Compact polarimetric synthetic aperture radar for monitoring soil moisture condition

    NASA Astrophysics Data System (ADS)

    Merzouki, A.; McNairn, H.; Powers, J.; Friesen, M.

    2017-12-01

    Coarse resolution soil moisture maps are currently operationally delivered by ESA's SMOS and NASA's SMAP passive microwaves sensors. Despite this evolution, operational soil moisture monitoring at the field scale remains challenging. A number of factors contribute to this challenge including the complexity of the retrieval that requires advanced SAR systems with enhanced temporal revisit capabilities. Since the launch of RADARSAT-2 in 2007, Agriculture and Agri-Food Canada (AAFC) has been evaluating the accuracy of these data for estimating surface soil moisture. Thus, a hybrid (multi-angle/multi-polarization) retrieval approach was found well suited for the planned RADARSAT Constellation Mission (RCM) considering the more frequent relook expected with the three satellite configuration. The purpose of this study is to evaluate the capability of C-band CP data to estimate soil moisture over agricultural fields, in anticipation of the launch of RCM. In this research we introduce a new CP approach based on the IEM and simulated RCM CP mode intensities from RADARSAT-2 images acquired at different dates. The accuracy of soil moisture retrieval from the proposed multi-polarization and hybrid methods will be contrasted with that from a more conventional quad-pol approach, and validated against in situ measurements by pooling data collected over AAFC test sites in Ontario, Manitoba and Saskatchewan, Canada.

  1. One step DNA assembly for combinatorial metabolic engineering.

    PubMed

    Coussement, Pieter; Maertens, Jo; Beauprez, Joeri; Van Bellegem, Wouter; De Mey, Marjan

    2014-05-01

    The rapid and efficient assembly of multi-step metabolic pathways for generating microbial strains with desirable phenotypes is a critical procedure for metabolic engineering, and remains a significant challenge in synthetic biology. Although several DNA assembly methods have been developed and applied for metabolic pathway engineering, many of them are limited by their suitability for combinatorial pathway assembly. The introduction of transcriptional (promoters), translational (ribosome binding site (RBS)) and enzyme (mutant genes) variability to modulate pathway expression levels is essential for generating balanced metabolic pathways and maximizing the productivity of a strain. We report a novel, highly reliable and rapid single strand assembly (SSA) method for pathway engineering. The method was successfully optimized and applied to create constructs containing promoter, RBS and/or mutant enzyme libraries. To demonstrate its efficiency and reliability, the method was applied to fine-tune multi-gene pathways. Two promoter libraries were simultaneously introduced in front of two target genes, enabling orthogonal expression as demonstrated by principal component analysis. This shows that SSA will increase our ability to tune multi-gene pathways at all control levels for the biotechnological production of complex metabolites, achievable through the combinatorial modulation of transcription, translation and enzyme activity. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  2. Multi-Objective Algorithm for Blood Supply via Unmanned Aerial Vehicles to the Wounded in an Emergency Situation.

    PubMed

    Wen, Tingxi; Zhang, Zhongnan; Wong, Kelvin K L

    2016-01-01

    Unmanned aerial vehicle (UAV) has been widely used in many industries. In the medical environment, especially in some emergency situations, UAVs play an important role such as the supply of medicines and blood with speed and efficiency. In this paper, we study the problem of multi-objective blood supply by UAVs in such emergency situations. This is a complex problem that includes maintenance of the supply blood's temperature model during transportation, the UAVs' scheduling and routes' planning in case of multiple sites requesting blood, and limited carrying capacity. Most importantly, we need to study the blood's temperature change due to the external environment, the heating agent (or refrigerant) and time factor during transportation, and propose an optimal method for calculating the mixing proportion of blood and appendage in different circumstances and delivery conditions. Then, by introducing the idea of transportation appendage into the traditional Capacitated Vehicle Routing Problem (CVRP), this new problem is proposed according to the factors of distance and weight. Algorithmically, we use the combination of decomposition-based multi-objective evolutionary algorithm and local search method to perform a series of experiments on the CVRP public dataset. By comparing our technique with the traditional ones, our algorithm can obtain better optimization results and time performance.

  3. An extended diffraction tomography method for quantifying structural damage using numerical Green's functions.

    PubMed

    Chan, Eugene; Rose, L R Francis; Wang, Chun H

    2015-05-01

    Existing damage imaging algorithms for detecting and quantifying structural defects, particularly those based on diffraction tomography, assume far-field conditions for the scattered field data. This paper presents a major extension of diffraction tomography that can overcome this limitation and utilises a near-field multi-static data matrix as the input data. This new algorithm, which employs numerical solutions of the dynamic Green's functions, makes it possible to quantitatively image laminar damage even in complex structures for which the dynamic Green's functions are not available analytically. To validate this new method, the numerical Green's functions and the multi-static data matrix for laminar damage in flat and stiffened isotropic plates are first determined using finite element models. Next, these results are time-gated to remove boundary reflections, followed by discrete Fourier transform to obtain the amplitude and phase information for both the baseline (damage-free) and the scattered wave fields. Using these computationally generated results and experimental verification, it is shown that the new imaging algorithm is capable of accurately determining the damage geometry, size and severity for a variety of damage sizes and shapes, including multi-site damage. Some aspects of minimal sensors requirement pertinent to image quality and practical implementation are also briefly discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Data on master regulators and transcription factor binding sites found by upstream analysis of multi-omics data on methotrexate resistance of colon cancer.

    PubMed

    Kel, AlexanderE

    2017-02-01

    Computational analysis of master regulators through the search for transcription factor binding sites followed by analysis of signal transduction networks of a cell is a new approach of causal analysis of multi-omics data. This paper contains results on analysis of multi-omics data that include transcriptomics, proteomics and epigenomics data of methotrexate (MTX) resistant colon cancer cell line. The data were used for analysis of mechanisms of resistance and for prediction of potential drug targets and promising compounds for reverting the MTX resistance of these cancer cells. We present all results of the analysis including the lists of identified transcription factors and their binding sites in genome and the list of predicted master regulators - potential drug targets. This data was generated in the study recently published in the article "Multi-omics "Upstream Analysis" of regulatory genomic regions helps identifying targets against methotrexate resistance of colon cancer" (Kel et al., 2016) [4]. These data are of interest for researchers from the field of multi-omics data analysis and for biologists who are interested in identification of novel drug targets against NTX resistance.

  5. Initial clinical testing of a multi-spectral imaging system built on a smartphone platform

    NASA Astrophysics Data System (ADS)

    Mink, Jonah W.; Wexler, Shraga; Bolton, Frank J.; Hummel, Charles; Kahn, Bruce S.; Levitz, David

    2016-03-01

    Multi-spectral imaging systems are often expensive and bulky. An innovative multi-spectral imaging system was fitted onto a mobile colposcope, an imaging system built around a smartphone in order to image the uterine cervix from outside the body. The multi-spectral mobile colposcope (MSMC) acquires images at different wavelengths. This paper presents the clinical testing of MSMC imaging (technical validation of the MSMC system is described elsewhere 1 ). Patients who were referred to colposcopy following abnormal screening test (Pap or HPV DNA test) according to the standard of care were enrolled. Multi-spectral image sets of the cervix were acquired, consisting of images from the various wavelengths. Image acquisition took 1-2 sec. Areas suspected for dysplasia under white light imaging were biopsied, according to the standard of care. Biopsied sites were recorded on a clockface map of the cervix. Following the procedure, MSMC data was processed from the sites of biopsied sites. To date, the initial histopathological results are still outstanding. Qualitatively, structures in the cervical images were sharper at lower wavelengths than higher wavelengths. Patients tolerated imaging well. The result suggests MSMC holds promise for cervical imaging.

  6. Multi-view L2-SVM and its multi-view core vector machine.

    PubMed

    Huang, Chengquan; Chung, Fu-lai; Wang, Shitong

    2016-03-01

    In this paper, a novel L2-SVM based classifier Multi-view L2-SVM is proposed to address multi-view classification tasks. The proposed Multi-view L2-SVM classifier does not have any bias in its objective function and hence has the flexibility like μ-SVC in the sense that the number of the yielded support vectors can be controlled by a pre-specified parameter. The proposed Multi-view L2-SVM classifier can make full use of the coherence and the difference of different views through imposing the consensus among multiple views to improve the overall classification performance. Besides, based on the generalized core vector machine GCVM, the proposed Multi-view L2-SVM classifier is extended into its GCVM version MvCVM which can realize its fast training on large scale multi-view datasets, with its asymptotic linear time complexity with the sample size and its space complexity independent of the sample size. Our experimental results demonstrated the effectiveness of the proposed Multi-view L2-SVM classifier for small scale multi-view datasets and the proposed MvCVM classifier for large scale multi-view datasets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Multi-tap complex-coefficient incoherent microwave photonic filters based on optical single-sideband modulation and narrow band optical filtering.

    PubMed

    Sagues, Mikel; García Olcina, Raimundo; Loayssa, Alayn; Sales, Salvador; Capmany, José

    2008-01-07

    We propose a novel scheme to implement tunable multi-tap complex coefficient filters based on optical single sideband modulation and narrow band optical filtering. A four tap filter is experimentally demonstrated to highlight the enhanced tuning performance provided by complex coefficients. Optical processing is performed by the use of a cascade of four phase-shifted fiber Bragg gratings specifically fabricated for this purpose.

  8. Amanzi: An Open-Source Multi-process Simulator for Environmental Applications

    NASA Astrophysics Data System (ADS)

    Moulton, J. D.; Molins, S.; Johnson, J. N.; Coon, E.; Lipnikov, K.; Day, M.; Barker, E.

    2014-12-01

    The Advanced Simulation Capabililty for Environmental Management (ASCEM) program is developing an approach and open-source tool suite for standardized risk and performance assessments at legacy nuclear waste sites. These assessments begin with simplified models, and add geometric and geologic complexity as understanding is gained. The Platform toolsets (Akuna) generates these conceptual models and Amanzi provides the computational engine to perform the simulations, returning the results for analysis and visualization. In this presentation we highlight key elements of the design, algorithms and implementations used in Amanzi. In particular, the hierarchical and modular design is aligned with the coupled processes being sumulated, and naturally supports a wide range of model complexity. This design leverages a dynamic data manager and the synergy of two graphs (one from the high-level perspective of the models the other from the dependencies of the variables in the model) to enable this flexible model configuration at run time. Moreover, to model sites with complex hydrostratigraphy, as well as engineered systems, we are developing a dual unstructured/structured capability. Recently, these capabilities have been collected in a framework named Arcos, and efforts have begun to improve interoperability between the unstructured and structured AMR approaches in Amanzi. To leverage a range of biogeochemistry capability from the community (e.g., CrunchFlow, PFLOTRAN, etc.), a biogeochemistry interface library was developed called Alquimia. To ensure that Amanzi is truly an open-source community code we require a completely open-source tool chain for our development. We will comment on elements of this tool chain, including the testing and documentation development tools such as docutils, and Sphinx. Finally, we will show simulation results from our phased demonstrations, including the geochemically complex Savannah River F-Area seepage basins.

  9. Tunable complex-valued multi-tap microwave photonic filter based on single silicon-on-insulator microring resonator.

    PubMed

    Lloret, Juan; Sancho, Juan; Pu, Minhao; Gasulla, Ivana; Yvind, Kresten; Sales, Salvador; Capmany, José

    2011-06-20

    A complex-valued multi-tap tunable microwave photonic filter based on single silicon-on-insulator microring resonator is presented. The degree of tunability of the approach involving two, three and four taps is theoretical and experimentally characterized, respectively. The constraints of exploiting the optical phase transfer function of a microring resonator aiming at implementing complex-valued multi-tap filtering schemes are also reported. The trade-off between the degree of tunability without changing the free spectral range and the number of taps is studied in-depth. Different window based scenarios are evaluated for improving the filter performance in terms of the side-lobe level.

  10. Development of a Multi-Target Contingency Management Intervention for HIV Positive Substance Users.

    PubMed

    Stitzer, Maxine; Calsyn, Donald; Matheson, Timothy; Sorensen, James; Gooden, Lauren; Metsch, Lisa

    2017-01-01

    Contingency management (CM) interventions generally target a single behavior such as attendance or drug use. However, disease outcomes are mediated by complex chains of both healthy and interfering behaviors enacted over extended periods of time. This paper describes a novel multi-target contingency management (CM) program developed for use with HIV positive substance users enrolled in a CTN multi-site study (0049 Project HOPE). Participants were randomly assigned to usual care (referral to health care and SUD treatment) or 6-months strength-based patient navigation interventions with (PN+CM) or without (PN only) the CM program. Primary outcome of the trial was viral load suppression at 12-months post-randomization. Up to $1160 could be earned over 6 months under escalating schedules of reinforcement. Earnings were divided among eight CM targets; two PN-related (PN visits; paperwork completion; 26% of possible earnings), four health-related (HIV care visits, lab blood draw visits, medication check, viral load suppression; 47% of possible earnings) and two drug-use abatement (treatment entry; submission of drug negative UAs; 27% of earnings). The paper describes rationale for selection of targets, pay amounts and pay schedules. The CM program was compatible with and fully integrated into the PN intervention. The study design will allow comparison of behavioral and health outcomes for participants receiving PN with and without CM; results will inform future multi-target CM development. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Interracial Contact and Racial Constancy: A Multi-Site Study of Racial Intergroup Bias in 3-5 Year Old Anglo-British Children

    ERIC Educational Resources Information Center

    Rutland, Adam; Cameron, Lindsey; Bennett, Laura; Ferrell, Jennifer

    2005-01-01

    This paper examined the influence of interracial contact and racial constancy on the racial intergroup bias of young Anglo-British children. This multi-site study was conducted in areas of Great Britain that varied in terms of racial diversity. The study also investigated whether preschool children express bias on positive, but not negative,…

  12. MULTI-SITE EVALUATIONS OF CANDIDATE METHODOLOGIES FOR DETERMINING COARSE PARTICULATE (PM 10-2.5) CONCENTRATIONS: AUGUST 2005 UPDATED REPORT REGARDING SECOND-GENERATION AND NEW PM 10-2.5 SAMPLERS

    EPA Science Inventory

    Multi-site field studies were conducted to evaluate the performance of sampling methods for measuring the coarse fraction of PM10 (PM10 2.5) in ambient air. The field studies involved the use of both time-integrated filter-based and direct continuous methods. Despite operationa...

  13. Sediment and Hydraulic Measurements with Computed Bed Load on the Missouri River, Sioux City to Hermann, 2014

    DTIC Science & Technology

    2017-05-01

    all sites were surveyed three times, separated by at least 4 weeks (or 20% flow difference) between surveys . Multi-beam, acoustic Doppler current...10 3.4 Multi-beam surveys ...37 4.4 Multi-beam surveys

  14. Downscaling the Local Weather Above Glaciers in Complex Topography

    NASA Astrophysics Data System (ADS)

    Horak, Johannes; Hofer, Marlis; Gutmann, Ethan; Gohm, Alexander; Rotach, Mathias

    2017-04-01

    Glaciers have experienced a substantial ice-volume loss during the 20th century. To study their response to climate change, process-based glacier mass-balance models (PBGMs) are employed, which require a faithful representation of the state of the atmosphere above the glacier at high spatial and temporal resolution. Glaciers are usually located in complex topography where weather stations are scarce or not existent at all due to the remoteness of such sites and the associated high cost of maintenance. Furthermore. the effective resolution of global circulation models is too large to adequately capture the local topography and represent local weather, which is prerequisite for atmospheric input used by PBGMs. Dynamical downscaling is a physically consistent but computationally expensive approach to bridge the scale gap between GCM output and input needed by PBGMs, while statistical downscaling is faster but requires measurements for training. Both methods have their merits, however, a computationally frugal approach that does not rely on measurements is desirable, especially for long term studies of glacier response to future climate. In this study the intermediate complexity atmospheric research model (ICAR) is employed (Gutmann et al., 2016). It simplifies the wind field physics by relying on analytical solutions derived with linear theory. ICAR then advects atmospheric quantities within this wind field. This allows for computationally fast downscaling and yields a physically consistent set of atmospheric variables. First results obtained from downscaling air temperature, precipitation amount, relative humidity and wind speed to 4 × 4 km2 are presented. Preliminary ICAR is applied for a six month simulation period during five years and evaluated for three domains located in very distinct climates, namely the Southern Alps of New Zealand, the Cordillera Blanca in Peru and the European Alps using ERA Interim reanalysis data (ERAI) as forcing data set. The evaluation is based on determining the added value of the ICAR simulations - with ERAI output as a reference - in representing the local-scale weather measured at several automatic weather stations. For precipitation amount in particular, data by the Global Precipitation Measurement project are used in a fuzzy verification approach. The results indicate that ICAR provides added value for the Southern Alps of New Zealand in the case of precipitation and relative humidity, for the Cordillera Blanca and the European Alps for wind speed and, at certain locations in the European Alps, for precipitation. In order to more comprehensively investigate the physical plausibility of skill obtained for specific weather situations, the spatio-temporal evolution of the wind field resulting from the ICAR dynamics is analysed for individual case studies. To the authors knowledge this is the first study that specifically investigates the multi-variable consistency of ICAR for different climates, an important prerequisite for all applications which require multi-variable or multi-site input. References: Gutmann, E., Barstad, I., Clark, M., Arnold, J., and Rasmussen, R. (2016). The Intermediate Complexity Atmospheric Research Model (ICAR). Journal of Hydrometeorology, 17(3), 957-973.

  15. A multi-institutional study of independent calculation verification in inhomogeneous media using a simple and effective method of heterogeneity correction integrated with the Clarkson method.

    PubMed

    Jinno, Shunta; Tachibana, Hidenobu; Moriya, Shunsuke; Mizuno, Norifumi; Takahashi, Ryo; Kamima, Tatsuya; Ishibashi, Satoru; Sato, Masanori

    2018-05-21

    In inhomogeneous media, there is often a large systematic difference in the dose between the conventional Clarkson algorithm (C-Clarkson) for independent calculation verification and the superposition-based algorithms of treatment planning systems (TPSs). These treatment site-dependent differences increase the complexity of the radiotherapy planning secondary check. We developed a simple and effective method of heterogeneity correction integrated with the Clarkson algorithm (L-Clarkson) to account for the effects of heterogeneity in the lateral dimension, and performed a multi-institutional study to evaluate the effectiveness of the method. In the method, a 2D image reconstructed from computed tomography (CT) images is divided according to lines extending from the reference point to the edge of the multileaf collimator (MLC) or jaw collimator for each pie sector, and the radiological path length (RPL) of each line is calculated on the 2D image to obtain a tissue maximum ratio and phantom scatter factor, allowing the dose to be calculated. A total of 261 plans (1237 beams) for conventional breast and lung treatments and lung stereotactic body radiotherapy were collected from four institutions. Disagreements in dose between the on-site TPSs and a verification program using the C-Clarkson and L-Clarkson algorithms were compared. Systematic differences with the L-Clarkson method were within 1% for all sites, while the C-Clarkson method resulted in systematic differences of 1-5%. The L-Clarkson method showed smaller variations. This heterogeneity correction integrated with the Clarkson algorithm would provide a simple evaluation within the range of -5% to +5% for a radiotherapy plan secondary check.

  16. A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

    PubMed

    Beauchesne, Patrick; Agarwal, Sabrina C

    2017-09-01

    One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed. © 2017 Wiley Periodicals, Inc.

  17. Patients come from populations and populations contain patients. A two-stage scientific and ethics review: The next adaptation for single institutional review boards.

    PubMed

    Knopman, David; Alford, Eli; Tate, Kaitlin; Long, Mark; Khachaturian, Ara S

    2017-08-01

    For nearly 50 years, institutional review boards (IRB) and independent ethics committees have featured local oversight as a core function of research ethics reviews. However growing complexity in Alzheimer's clinical research suggests current approaches to research volunteer safety is hampering development of new therapeutics. As a partial response to this challenge, the NIH has mandated that all NIH-funded multi-site studies will use a single Institutional Review Board. The perspective describes a joint program to provide a single IRB of record (sIRB) for phases of multi-site studies. The approach follows two steps. One, an expert Scientific Review Committee (SRC) of senior researchers in the field will conduct the review principally of scientific merit, significance, feasibility, and the likelihood of meaningful results. The second step will be the IRB's regulatory and ethics review. The IRB will apply appropriate regulatory criteria for approval including minimization of risks to subjects and risks reasonable in relation to anticipated benefits, equitable subject selection, informed consent, protections for vulnerable populations, and application of local context considerations, among others. There is a steady demand for scientific, ethical and regulatory review of planned Alzheimer's studies. As of January 15, 2017, there are nearly 400 open studies, Phase II and III, industry and NIH sponsored trials on disease indications affecting memory, movement and mood in the US. The effort will initially accept protocols for studies of Alzheimer's disease, dementia, and related disorders effecting memory, movement and mood. Future aims will be to provide scientific review and, where applicable, regulatory and ethical review in an international context outside North America with sites possibly in Asia, Europe and Australia. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  18. Describing complex cells in primary visual cortex: a comparison of context and multi-filter LN models.

    PubMed

    Westö, Johan; May, Patrick J C

    2018-05-02

    Receptive field (RF) models are an important tool for deciphering neural responses to sensory stimuli. The two currently popular RF models are multi-filter linear-nonlinear (LN) models and context models. Models are, however, never correct and they rely on assumptions to keep them simple enough to be interpretable. As a consequence, different models describe different stimulus-response mappings, which may or may not be good approximations of real neural behavior. In the current study, we take up two tasks: First, we introduce new ways to estimate context models with realistic nonlinearities, that is, with logistic and exponential functions. Second, we evaluate context models and multi-filter LN models in terms of how well they describe recorded data from complex cells in cat primary visual cortex. Our results, based on single-spike information and correlation coefficients, indicate that context models outperform corresponding multi-filter LN models of equal complexity (measured in terms of number of parameters), with the best increase in performance being achieved by the novel context models. Consequently, our results suggest that the multi-filter LN-model framework is suboptimal for describing the behavior of complex cells: the context-model framework is clearly superior while still providing interpretable quantizations of neural behavior.

  19. Multi-Site Diagnostic Classification of Schizophrenia Using Discriminant Deep Learning with Functional Connectivity MRI.

    PubMed

    Zeng, Ling-Li; Wang, Huaning; Hu, Panpan; Yang, Bo; Pu, Weidan; Shen, Hui; Chen, Xingui; Liu, Zhening; Yin, Hong; Tan, Qingrong; Wang, Kai; Hu, Dewen

    2018-04-01

    A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources) was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the "disconnectivity" model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.

  20. Building a mechanistic understanding of predation with GPS-based movement data.

    PubMed

    Merrill, Evelyn; Sand, Håkan; Zimmermann, Barbara; McPhee, Heather; Webb, Nathan; Hebblewhite, Mark; Wabakken, Petter; Frair, Jacqueline L

    2010-07-27

    Quantifying kill rates and sources of variation in kill rates remains an important challenge in linking predators to their prey. We address current approaches to using global positioning system (GPS)-based movement data for quantifying key predation components of large carnivores. We review approaches to identify kill sites from GPS movement data as a means to estimate kill rates and address advantages of using GPS-based data over past approaches. Despite considerable progress, modelling the probability that a cluster of GPS points is a kill site is no substitute for field visits, but can guide our field efforts. Once kill sites are identified, time spent at a kill site (handling time) and time between kills (killing time) can be determined. We show how statistical models can be used to investigate the influence of factors such as animal characteristics (e.g. age, sex, group size) and landscape features on either handling time or killing efficiency. If we know the prey densities along paths to a kill, we can quantify the 'attack success' parameter in functional response models directly. Problems remain in incorporating the behavioural complexity derived from GPS movement paths into functional response models, particularly in multi-prey systems, but we believe that exploring the details of GPS movement data has put us on the right path.

  1. Synergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.

    PubMed

    Gri, G; Savio, D; Trinchieri, G; Ma, X

    1998-03-13

    Monocytes/macrophages produce interleukin-12 (IL-12) in response to pathogenic stimulation, whereas most Epstein-Barr virus-transformed (EBV+) B cells constitutively secrete IL-12. The molecular mechanism regulating the constitutive IL-12 gene expression in EBV+ B cells has not been addressed. In this study, using the EBV+ B cell line RPMI-8866, we localized to the human IL-12 p40 promoter two essential cis elements, the NFkappaB site and the Ets site. The NFkappaB site was shown to interact with members of the NFkappaB family: p50 and c-Rel. The Ets site constitutively bound a multi-component Ets-2-containing complex. While the NFkappaB and Ets sites appear equally critical for inducible p40 promoter activity in macrophage cell lines, NFkappaB plays a more dominant role in the constitutive p40 promoter activity in EBV+ B cells. Transient expression of Ets-2 and c-Rel in B, T, and monocytic cell lines synergistically activated the IL-12 p40 promoter, apparently overcoming the requirement for cell type- or stimulant-specific transcription factors. These data provide new evidence that full activation of the human IL-12 p40 promoter may result primarily from the interplay between NFkappaB and Ets family members.

  2. Landfill Site Selection by AHP Based Multi-criteria Decision Making Tool: A Case Study in Kolkata, India

    NASA Astrophysics Data System (ADS)

    Majumdar, Ankush; Hazra, Tumpa; Dutta, Amit

    2017-09-01

    This work presents a Multi-criteria Decision Making (MCDM) tool to select a landfill site from three candidate sites proposed for Kolkata Municipal Corporation (KMC) area that complies with accessibility, receptor, environment, public acceptability, geological and economic criteria. Analytical Hierarchy Process has been used to solve the MCDM problem. Suitability of the three sites (viz. Natagachi, Gangajoara and Kharamba) as landfills as proposed by KMC has been checked by Landfill Site Sensitivity Index (LSSI) as well as Economic Viability Index (EVI). Land area availability for disposing huge quantity of Municipal Solid Waste for the design period has been checked. Analysis of the studied sites show that they are moderately suitable for landfill facility construction as both LSSI and EVI scores lay between 300 and 750. The proposed approach represents an effective MCDM tool for siting sanitary landfill in growing metropolitan cities of developing countries like India.

  3. A GIS-BASED MULTI-CRITERIA EVALUATION SYSTEM FOR SELECTION OF LANDFILL SITES: a case study from Abu Dhabi, United Arab Emirates

    NASA Astrophysics Data System (ADS)

    Issa, S. M.; Shehhi, B. Al

    2012-07-01

    Landfill sites receive 92% of total annual solid waste produced by municipalities in the emirate of Abu Dhabi. In this study, candidate sites for an appropriate landfill location for the Abu Dhabi municipal area are determined by integrating geographic information systems (GIS) and multi-criteria evaluation (MCE) analysis. To identify appropriate landfill sites, eight input map layers including proximity to urban areas, proximity to wells and water table depth, geology and topography, proximity to touristic and archeological sites, distance from roads network, distance from drainage networks, and land slope are used in constraint mapping. A final map was generated which identified potential areas showing suitability for the location of the landfill site. Results revealed that 30% of the study area was identified as highly suitable, 25% as suitable, and 45% as unsuitable. The selection of the final landfill site, however, requires further field research.

  4. Multi-scale habitat selection in highly territorial bird species: Exploring the contribution of nest, territory and landscape levels to site choice in breeding rallids (Aves: Rallidae)

    NASA Astrophysics Data System (ADS)

    Jedlikowski, Jan; Chibowski, Piotr; Karasek, Tomasz; Brambilla, Mattia

    2016-05-01

    Habitat selection often involves choices made at different spatial scales, but the underlying mechanisms are still poorly understood, and studies that investigate the relative importance of individual scales are rare. We investigated the effect of three spatial scales (landscape, territory, nest-site) on the occurrence pattern of little crake Zapornia parva and water rail Rallus aquaticus at 74 ponds in the Masurian Lakeland, Poland. Habitat structure, food abundance and water chemical parameters were measured at nests and random points within landscape plots (from 300-m to 50-m radius), territory (14-m) and nest-site plots (3-m). Regression analyses suggested that the most relevant scale was territory level, followed by landscape, and finally by nest-site for both species. Variation partitioning confirmed this pattern for water rail, but also highlighted the importance of nest-site (the level explaining the highest share of unique variation) for little crake. The most important variables determining the occurrence of both species were water body fragmentation (landscape), vegetation density (territory) and water depth (at territory level for little crake, and at nest-site level for water rail). Finally, for both species multi-scale models including factors from different levels were more parsimonious than single-scale ones, i.e. habitat selection was likely a multi-scale process. The importance of particular spatial scales seemed more related to life-history traits than to the extent of the scales considered. In the case of our study species, the territory level was highly important likely because both rallids have to obtain all the resources they need (nest site, food and mates) in relatively small areas, the multi-purpose territories they defend.

  5. [Nitrogen stress measurement of canola based on multi-spectral charged coupled device imaging sensor].

    PubMed

    Feng, Lei; Fang, Hui; Zhou, Wei-Jun; Huang, Min; He, Yong

    2006-09-01

    Site-specific variable nitrogen application is one of the major precision crop production management operations. Obtaining sufficient crop nitrogen stress information is essential for achieving effective site-specific nitrogen applications. The present paper describes the development of a multi-spectral nitrogen deficiency sensor, which uses three channels (green, red, near-infrared) of crop images to determine the nitrogen level of canola. This sensor assesses the nitrogen stress by means of estimated SPAD value of the canola based on canola canopy reflectance sensed using three channels (green, red, near-infrared) of the multi-spectral camera. The core of this investigation is the calibration methods between the multi-spectral references and the nitrogen levels in crops measured using a SPAD 502 chlorophyll meter. Based on the results obtained from this study, it can be concluded that a multi-spectral CCD camera can provide sufficient information to perform reasonable SPAD values estimation during field operations.

  6. Multi-criteria ranking and receptor modelling of airborne fine particles at three sites in the Pearl River Delta region of China.

    PubMed

    Friend, Adrian J; Ayoko, Godwin A; Guo, Hai

    2011-01-15

    The multi-criteria decision making methods, Preference Ranking Organization METHods for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA), and the two-way Positive Matrix Factorization (PMF) receptor model were applied to airborne fine particle compositional data collected at three sites in Hong Kong during two monitoring campaigns held from November 2000 to October 2001 and November 2004 to October 2005. PROMETHEE/GAIA indicated that the three sites were worse during the later monitoring campaign, and that the order of the air quality at the sites during each campaign was: rural site>urban site>roadside site. The PMF analysis on the other hand, identified 6 common sources at all of the sites (diesel vehicle, fresh sea salt, secondary sulphate, soil, aged sea salt and oil combustion) which accounted for approximately 68.8±8.7% of the fine particle mass at the sites. In addition, road dust, gasoline vehicle, biomass burning, secondary nitrate, and metal processing were identified at some of the sites. Secondary sulphate was found to be the highest contributor to the fine particle mass at the rural and urban sites with vehicle emission as a high contributor to the roadside site. The PMF results are broadly similar to those obtained in a previous analysis by PCA/APCS. However, the PMF analysis resolved more factors at each site than the PCA/APCS. In addition, the study demonstrated that combined results from multi-criteria decision making analysis and receptor modelling can provide more detailed information that can be used to formulate the scientific basis for mitigating air pollution in the region. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. The evolving landscape and climate of western Flores: an environmental context for the archaeological site of Liang Bua.

    PubMed

    Westaway, K E; Roberts, R G; Sutikna, T; Morwood, M J; Drysdale, R; Zhao, J-x; Chivas, A R

    2009-11-01

    The rapidly changing landscape of the eastern Indonesian archipelago has evolved at a pace dictated by its tropical climate and its geological and tectonic history. This has produced accelerated karstification, flights of alluvial terraces, and complex, multi-level cave systems. These cave systems sometimes contain a wealth of archaeological evidence, such as the almost complete skeleton of Homo floresiensis found at the site of Liang Bua in western Flores, but this information can only be understood in the context of the geomorphic history of the cave, and the more general geological, tectonic, and environmental histories of the river valley and region. Thus, a reconstruction of the landscape history of the Wae Racang valley using speleothems, geological structure, tectonic uplift, karst, cave, and terrace development, provides the necessary evidence to determine the formation, age, evolution, and influences on the site. This evidence suggests that Liang Bua was formed as two subterranean chambers approximately 600ka, but could not be occupied until approximately 190ka when the Wae Racang wandered to the southern side of the valley, exposing the chamber and depositing alluvial deposits containing artifacts. During the next approximately 190k.yr., the chambers coalesced and evolved into a multi-level and interconnected cave that was subjected to channel erosion and pooling events by the development of sinkholes. The domed morphology of the front chamber accumulated deep sediments containing well stratified archaeological and faunal remains, but ponded water in the chamber further prevented hominin use of the cave until approximately 100ka. These chambers were periodically influenced by river inundation and volcanic activity, whereas the area outside the cave was greatly influenced by glacial phases, which changed humid forest environments into grassland environments. This combined evidence has important implications for the archaeological interpretation of the site.

  8. A multi-omics based ecological analysis of coastal marine sediments from Gladstone, in Australia's Central Queensland, and Heron Island, a nearby fringing platform reef.

    PubMed

    Beale, D J; Crosswell, J; Karpe, A V; Ahmed, W; Williams, M; Morrison, P D; Metcalfe, S; Staley, C; Sadowsky, M J; Palombo, E A; Steven, A D L

    2017-12-31

    The impact of anthropogenic factors arising from point and non-point pollution sources at a multi commodity marine port and its surrounding ecosystems were studied using sediment samples collected from a number of onshore (Gladstone Harbour and Facing Island) and offshore (Heron Island and Fitzroy Reefs) sites in Australia's Central Queensland. Sediment samples were analyzed for trace metals, organic carbon, polycyclic aromatic hydrocarbons (PAH), emerging chemicals of concern (ECC) and sterols. Similarly, the biological and biochemical interaction between the reef and its environment was analyzed by the multi-omic tools of next-generation sequencing characterization of the bacterial community and microbial community metabolic profiling. Overall, the trace elements were observed at the lower end of the Australian environmental guideline values at the offshore sites, while higher values were observed for the onshore locations Nickel and copper were observed above the high trigger value threshold at the onshore sites. The levels of PAH were below limits of detection across all sites. However, some of the ECC and sterols were observed at higher concentrations at both onshore and offshore locations, notably, the cholesterol family sterols and 17α-ethynylestradiol. Multi-omic analyses also indicated possible thermal and photo irradiation stressors on the bacterial communities at all the tested sites. The observed populations of γ-proteobacteria were found in combination with an increased pool of fatty acids that indicate fatty acid synthesis and utilisation of the intermediates of the shikimate pathways. This study demonstrates the value of applying a multi-omics approach for ecological assessments, in which a more detailed assessment of physical and chemical contaminants and their impact on the community bacterial biome is obtained. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  9. Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI.

    PubMed

    Turkbey, Baris; Xu, Sheng; Kruecker, Jochen; Locklin, Julia; Pang, Yuxi; Shah, Vijay; Bernardo, Marcelino; Baccala, Angelo; Rastinehad, Ardeshir; Benjamin, Compton; Merino, Maria J; Wood, Bradford J; Choyke, Peter L; Pinto, Peter A

    2011-03-29

    During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.

  10. Site Suitability Analysis for Beekeeping via Analythical Hyrearchy Process, Konya Example

    NASA Astrophysics Data System (ADS)

    Sarı, F.; Ceylan, D. A.

    2017-11-01

    Over the past decade, the importance of the beekeeping activities has been emphasized in the field of biodiversity, ecosystems, agriculture and human health. Thus, efficient management and deciding correct beekeeping activities seems essential to maintain and improve productivity and efficiency. Due to this importance, considering the economic contributions to the rural area, the need for suitability analysis concept has been revealed. At this point, Multi Criteria Decision Analysis (MCDA) and Geographical Information Systems (GIS) integration provides efficient solutions to the complex structure of decision- making process for beekeeping activities. In this study, site suitability analysis via Analytical Hierarchy Process (AHP) was carried out for Konya city in Turkey. Slope, elevation, aspect, distance to water resources, roads and settlements, precipitation and flora criteria are included to determine suitability. The requirements, expectations and limitations of beekeeping activities are specified with the participation of experts and stakeholders. The final suitability map were validated with existing 117 beekeeping locations and Turkish Statistical Institute 2016 beekeeping statistics for Konya province.

  11. Kinome signaling through regulated protein-protein interactions in normal and cancer cells.

    PubMed

    Pawson, Tony; Kofler, Michael

    2009-04-01

    The flow of molecular information through normal and oncogenic signaling pathways frequently depends on protein phosphorylation, mediated by specific kinases, and the selective binding of the resulting phosphorylation sites to interaction domains present on downstream targets. This physical and functional interplay of catalytic and interaction domains can be clearly seen in cytoplasmic tyrosine kinases such as Src, Abl, Fes, and ZAP-70. Although the kinase and SH2 domains of these proteins possess similar intrinsic properties of phosphorylating tyrosine residues or binding phosphotyrosine sites, they also undergo intramolecular interactions when linked together, in a fashion that varies from protein to protein. These cooperative interactions can have diverse effects on substrate recognition and kinase activity, and provide a variety of mechanisms to link the stimulation of catalytic activity to substrate recognition. Taken together, these data have suggested how protein kinases, and the signaling pathways in which they are embedded, can evolve complex properties through the stepwise linkage of domains within single polypeptides or multi-protein assemblies.

  12. Distribution and trajectories of floating and benthic marine macrolitter in the south-eastern North Sea.

    PubMed

    Gutow, Lars; Ricker, Marcel; Holstein, Jan M; Dannheim, Jennifer; Stanev, Emil V; Wolff, Jörg-Olaf

    2018-06-01

    In coastal waters the identification of sources, trajectories and deposition sites of marine litter is often hampered by the complex oceanography of shallow shelf seas. We conducted a multi-annual survey on litter at the sea surface and on the seafloor in the south-eastern North Sea. Bottom trawling was identified as a major source of marine litter. Oceanographic modelling revealed that the distribution of floating litter in the North Sea is largely determined by the site of origin of floating objects whereas the trajectories are strongly influenced by wind drag. Methods adopted from species distribution modelling indicated that resuspension of benthic litter and near-bottom transport processes strongly influence the distribution of litter on the seafloor. Major sink regions for floating marine litter were identified at the west coast of Denmark and in the Skagerrak. Our results may support the development of strategies to reduce the pollution of the North Sea. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Particle Deposition in Human Lungs due to Varying Cross-Sectional Ellipticity of Left and Right Main Bronchi

    NASA Astrophysics Data System (ADS)

    Roth, Steven; Oakes, Jessica; Shadden, Shawn

    2015-11-01

    Particle deposition in the human lungs can occur with every breathe. Airbourne particles can range from toxic constituents (e.g. tobacco smoke and air pollution) to aerosolized particles designed for drug treatment (e.g. insulin to treat diabetes). The effect of various realistic airway geometries on complex flow structures, and thus particle deposition sites, has yet to be extensively investigated using computational fluid dynamics (CFD). In this work, we created an image-based geometric airway model of the human lung and performed CFD simulations by employing multi-domain methods. Following the flow simulations, Lagrangian particle tracking was used to study the effect of cross-sectional shape on deposition sites in the conducting airways. From a single human lung model, the cross-sectional ellipticity (the ratio of major and minor diameters) of the left and right main bronchi was varied systematically from 2:1 to 1:1. The influence of the airway ellipticity on the surrounding flow field and particle deposition was determined.

  14. Regulation of chromatin organization and inducible gene expression by a Drosophila insulator

    PubMed Central

    Wood, Ashley M.; Van Bortle, Kevin; Ramos, Edward; Takenaka, Naomi; Rohrbaugh, Margaret; Jones, Brian C.; Jones, Keith C.; Corces, Victor G.

    2011-01-01

    SUMMARY Insulators are multi-protein-DNA complexes thought to affect gene expression by mediating inter- and intra-chromosomal interactions. Drosophila insulators contain specific DNA binding proteins plus common components, such as CP190, that facilitate these interactions. Here we examine changes in the distribution of Drosophila insulator proteins during the heat-shock and ecdysone responses. We find that CP190 recruitment to insulator sites is the main regulatable step in controlling insulator function during heat shock. In contrast, both CP190 and DNA binding protein recruitment are regulated during the ecdysone response. CP190 is necessary to stabilize specific chromatin loops and for proper activation of transcription of genes regulated by this hormone. These findings suggest that cells may regulate recruitment of insulator proteins to the DNA in order to activate insulator activity at specific sites and create distinct patterns of nuclear organization that are necessary to achieve proper gene expression in response to different stimuli. PMID:21981916

  15. The problem of epistemic jurisdiction in global governance: The case of sustainability standards for biofuels.

    PubMed

    Winickoff, David E; Mondou, Matthieu

    2017-02-01

    While there is ample scholarly work on regulatory science within the state, or single-sited global institutions, there is less on its operation within complex modes of global governance that are decentered, overlapping, multi-sectorial and multi-leveled. Using a co-productionist framework, this study identifies 'epistemic jurisdiction' - the power to produce or warrant technical knowledge for a given political community, topical arena or geographical territory - as a central problem for regulatory science in complex governance. We explore these dynamics in the arena of global sustainability standards for biofuels. We select three institutional fora as sites of inquiry: the European Union's Renewable Energy Directive, the Roundtable on Sustainable Biomaterials, and the International Organization for Standardization. These cases allow us to analyze how the co-production of sustainability science responds to problems of epistemic jurisdiction in the global regulatory order. First, different problems of epistemic jurisdiction beset different standard-setting bodies, and these problems shape both the content of regulatory science and the procedures designed to make it authoritative. Second, in order to produce global regulatory science, technical bodies must manage an array of conflicting imperatives - including scientific virtue, due process and the need to recruit adoptees to perpetuate the standard. At different levels of governance, standard drafters struggle to balance loyalties to country, to company or constituency and to the larger project of internationalization. Confronted with these sometimes conflicting pressures, actors across the standards system quite self-consciously maneuver to build or retain authority for their forum through a combination of scientific adjustment and political negotiation. Third, the evidentiary demands of regulatory science in global administrative spaces are deeply affected by 1) a market for standards, in which firms and states can choose the cheapest sustainability certification, and 2) the international trade regime, in which the long shadow of WTO law exerts a powerful disciplining function.

  16. Four-dimensional characterization of inflow to and wakes from a multi-MW turbine: overview of the Turbine Wake and Inflow Characterization Study (TWICS2011)

    NASA Astrophysics Data System (ADS)

    Lundquist, J. K.; Banta, R. M.; Pichugina, Y.; Brewer, A.; Alvarez, R. J.; Sandberg, S. P.; Kelley, N. D.; Aitken, M.; Clifton, A.; Mirocha, J. D.

    2011-12-01

    To support substantial deployment of renewably-generated electricity from the wind, critical information about the variability of wind turbine wakes in the real atmosphere from multi-MW turbines is required. The assessment of the velocity deficit and turbulence associated with industrial-scale turbines is a major issue for wind farm design, particularly with respect to the optimization of the spacing between turbines. The significant velocity deficit and turbulence generated by upstream turbines can reduce the power production and produce harmful vibrations in downstream turbines, which can lead to excess maintenance costs. The complexity of wake effects depends on many factors arising from both hardware (turbine size, rotor speed, and blade geometry, etc.) and from meteorological considerations such as wind velocity, gradients of wind across the turbine rotor disk, atmospheric stability, and atmospheric turbulence. To characterize the relationships between the meteorological inflow and turbine wakes, a collaborative field campaign was designed and carried out at the Department of Energy's National Wind Technology Center (NREL/NWTC) in south Boulder, Colorado, in spring 2011. This site often experiences channeled flow with a consistent wind direction, enabling robust statistics of wake velocity deficits and turbulence enhancements. Using both in situ and remote sensing instrumentation, measurements upwind and downwind of multi-megawatt wind turbine in complex terrain quantified the variability of wind turbine inflow and wakes from an industrial-scale turbine. The turbine of interest has a rated power of 2.3 MW, a rotor diameter of 100m, and a hub height of 80m. In addition to several meteorological towers, one extending to hub height (80m) and another extending above the top of the rotor disk (135m), a Triton mini-sodar and a Windcube lidar characterized the inflow to the turbine and the variability across the site. The centerpiece instrument of the TWICS campaign was the NOAA High Resolution Doppler lidar (HRDL), a scanning lidar which captured three-dimensional images of the turbine inflow and wake. Over several weeks, 48+ hours of HRDL observations during a variety of wind speed and atmospheric stability conditions were collected using three scanning strategies. Wake features such as lofting, meandering, intersection with the ground, and expansion factors are identified and discussed. Observations of a remarkably long-distance wake are presented and compared with existing wake models.

  17. Mass discharge estimation from contaminated sites: Multi-model solutions for assessment of conceptual uncertainty

    NASA Astrophysics Data System (ADS)

    Thomsen, N. I.; Troldborg, M.; McKnight, U. S.; Binning, P. J.; Bjerg, P. L.

    2012-04-01

    Mass discharge estimates are increasingly being used in the management of contaminated sites. Such estimates have proven useful for supporting decisions related to the prioritization of contaminated sites in a groundwater catchment. Potential management options can be categorised as follows: (1) leave as is, (2) clean up, or (3) further investigation needed. However, mass discharge estimates are often very uncertain, which may hamper the management decisions. If option 1 is incorrectly chosen soil and water quality will decrease, threatening or destroying drinking water resources. The risk of choosing option 2 is to spend money on remediating a site that does not pose a problem. Choosing option 3 will often be safest, but may not be the optimal economic solution. Quantification of the uncertainty in mass discharge estimates can therefore greatly improve the foundation for selecting the appropriate management option. The uncertainty of mass discharge estimates depends greatly on the extent of the site characterization. A good approach for uncertainty estimation will be flexible with respect to the investigation level, and account for both parameter and conceptual model uncertainty. We propose a method for quantifying the uncertainty of dynamic mass discharge estimates from contaminant point sources on the local scale. The method considers both parameter and conceptual uncertainty through a multi-model approach. The multi-model approach evaluates multiple conceptual models for the same site. The different conceptual models consider different source characterizations and hydrogeological descriptions. The idea is to include a set of essentially different conceptual models where each model is believed to be realistic representation of the given site, based on the current level of information. Parameter uncertainty is quantified using Monte Carlo simulations. For each conceptual model we calculate a transient mass discharge estimate with uncertainty bounds resulting from the parametric uncertainty. To quantify the conceptual uncertainty from a given site, we combine the outputs from the different conceptual models using Bayesian model averaging. The weight for each model is obtained by integrating available data and expert knowledge using Bayesian belief networks. The multi-model approach is applied to a contaminated site. At the site a DNAPL (dense non aqueous phase liquid) spill consisting of PCE (perchloroethylene) has contaminated a fractured clay till aquitard overlaying a limestone aquifer. The exact shape and nature of the source is unknown and so is the importance of transport in the fractures. The result of the multi-model approach is a visual representation of the uncertainty of the mass discharge estimates for the site which can be used to support the management options.

  18. Cellulosome-based, Clostridium-derived multi-functional enzyme complexes for advanced biotechnology tool development: advances and applications.

    PubMed

    Hyeon, Jeong Eun; Jeon, Sang Duck; Han, Sung Ok

    2013-11-01

    The cellulosome is one of nature's most elegant and elaborate nanomachines and a key biological and biotechnological macromolecule that can be used as a multi-functional protein complex tool. Each protein module in the cellulosome system is potentially useful in an advanced biotechnology application. The high-affinity interactions between the cohesin and dockerin domains can be used in protein-based biosensors to improve both sensitivity and selectivity. The scaffolding protein includes a carbohydrate-binding module (CBM) that attaches strongly to cellulose substrates and facilitates the purification of proteins fused with the dockerin module through a one-step CBM purification method. Although the surface layer homology (SLH) domain of CbpA is not present in other strains, replacement of the cell surface anchoring domain allows a foreign protein to be displayed on the surface of other strains. The development of a hydrolysis enzyme complex is a useful strategy for consolidated bioprocessing (CBP), enabling microorganisms with biomass hydrolysis activity. Thus, the development of various configurations of multi-functional protein complexes for use as tools in whole-cell biocatalyst systems has drawn considerable attention as an attractive strategy for bioprocess applications. This review provides a detailed summary of the current achievements in Clostridium-derived multi-functional complex development and the impact of these complexes in various areas of biotechnology. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Translating Strategy, Values and Identities in Higher Education: The Case of Multi-Campus Systems

    ERIC Educational Resources Information Center

    Pinheiro, Rómulo; Charles, David; Jones, Glen

    2017-01-01

    Multi-campus university systems are not a new phenomenon. In their foundational analysis of multi-campus universities in the United States published in 1971, Lee and Bowen noted that almost 40% of American students were enroled in institutions that were part of multi-campus systems. The role of these complex multi-campus systems has continued to…

  20. Herbicide volatilization trumps runoff losses, a multi-year investigation

    USDA-ARS?s Scientific Manuscript database

    Surface runoff and volatilization are two processes critical to herbicide off-site transport. To determine the relevance of these off-site transport mechanisms, runoff and turbulent vapor fluxes were simultaneously monitored on the same site for eight years. Site location, herbicide formulations, ...

  1. The BioIntelligence Framework: a new computational platform for biomedical knowledge computing

    PubMed Central

    Farley, Toni; Kiefer, Jeff; Lee, Preston; Von Hoff, Daniel; Trent, Jeffrey M; Colbourn, Charles

    2013-01-01

    Breakthroughs in molecular profiling technologies are enabling a new data-intensive approach to biomedical research, with the potential to revolutionize how we study, manage, and treat complex diseases. The next great challenge for clinical applications of these innovations will be to create scalable computational solutions for intelligently linking complex biomedical patient data to clinically actionable knowledge. Traditional database management systems (DBMS) are not well suited to representing complex syntactic and semantic relationships in unstructured biomedical information, introducing barriers to realizing such solutions. We propose a scalable computational framework for addressing this need, which leverages a hypergraph-based data model and query language that may be better suited for representing complex multi-lateral, multi-scalar, and multi-dimensional relationships. We also discuss how this framework can be used to create rapid learning knowledge base systems to intelligently capture and relate complex patient data to biomedical knowledge in order to automate the recovery of clinically actionable information. PMID:22859646

  2. Structure of photosystem II and substrate binding at room temperature.

    PubMed

    Young, Iris D; Ibrahim, Mohamed; Chatterjee, Ruchira; Gul, Sheraz; Fuller, Franklin; Koroidov, Sergey; Brewster, Aaron S; Tran, Rosalie; Alonso-Mori, Roberto; Kroll, Thomas; Michels-Clark, Tara; Laksmono, Hartawan; Sierra, Raymond G; Stan, Claudiu A; Hussein, Rana; Zhang, Miao; Douthit, Lacey; Kubin, Markus; de Lichtenberg, Casper; Long Vo, Pham; Nilsson, Håkan; Cheah, Mun Hon; Shevela, Dmitriy; Saracini, Claudio; Bean, Mackenzie A; Seuffert, Ina; Sokaras, Dimosthenis; Weng, Tsu-Chien; Pastor, Ernest; Weninger, Clemens; Fransson, Thomas; Lassalle, Louise; Bräuer, Philipp; Aller, Pierre; Docker, Peter T; Andi, Babak; Orville, Allen M; Glownia, James M; Nelson, Silke; Sikorski, Marcin; Zhu, Diling; Hunter, Mark S; Lane, Thomas J; Aquila, Andy; Koglin, Jason E; Robinson, Joseph; Liang, Mengning; Boutet, Sébastien; Lyubimov, Artem Y; Uervirojnangkoorn, Monarin; Moriarty, Nigel W; Liebschner, Dorothee; Afonine, Pavel V; Waterman, David G; Evans, Gwyndaf; Wernet, Philippe; Dobbek, Holger; Weis, William I; Brunger, Axel T; Zwart, Petrus H; Adams, Paul D; Zouni, Athina; Messinger, Johannes; Bergmann, Uwe; Sauter, Nicholas K; Kern, Jan; Yachandra, Vittal K; Yano, Junko

    2016-12-15

    Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn 4 CaO 5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S 0 to S 4 ), in which S 1 is the dark-stable state and S 3 is the last semi-stable state before O-O bond formation and O 2 evolution. A detailed understanding of the O-O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site. Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S 1 ), two-flash illuminated (2F; S 3 -enriched), and ammonia-bound two-flash illuminated (2F-NH 3 ; S 3 -enriched) PS II. Although the recent 1.95 Å resolution structure of PS II at cryogenic temperature using an XFEL provided a damage-free view of the S 1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions, and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn 4 CaO 5 cluster in the S 2 and S 3 states. Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site. This approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms.

  3. Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling.

    PubMed

    Brand, Martin D

    2016-11-01

    This review examines the generation of reactive oxygen species by mammalian mitochondria, and the status of different sites of production in redox signaling and pathology. Eleven distinct mitochondrial sites associated with substrate oxidation and oxidative phosphorylation leak electrons to oxygen to produce superoxide or hydrogen peroxide: oxoacid dehydrogenase complexes that feed electrons to NAD + ; respiratory complexes I and III, and dehydrogenases, including complex II, that use ubiquinone as acceptor. The topologies, capacities, and substrate dependences of each site have recently clarified. Complex III and mitochondrial glycerol 3-phosphate dehydrogenase generate superoxide to the external side of the mitochondrial inner membrane as well as the matrix, the other sites generate superoxide and/or hydrogen peroxide exclusively in the matrix. These different site-specific topologies are important for redox signaling. The net rate of superoxide or hydrogen peroxide generation depends on the substrates present and the antioxidant systems active in the matrix and cytosol. The rate at each site can now be measured in complex substrate mixtures. In skeletal muscle mitochondria in media mimicking muscle cytosol at rest, four sites dominate, two in complex I and one each in complexes II and III. Specific suppressors of two sites have been identified, the outer ubiquinone-binding site in complex III (site III Qo ) and the site in complex I active during reverse electron transport (site I Q ). These suppressors prevent superoxide/hydrogen peroxide production from a specific site without affecting oxidative phosphorylation, making them excellent tools to investigate the status of the sites in redox signaling, and to suppress the sites to prevent pathologies. They allow the cellular roles of mitochondrial superoxide/hydrogen peroxide production to be investigated without catastrophic confounding bioenergetic effects. They show that sites III Qo and I Q are active in cells and have important roles in redox signaling (e.g. hypoxic signaling and ER-stress) and in causing oxidative damage in a variety of biological contexts. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Electronic Cigarette Marketing Online: a Multi-Site, Multi-Product Comparison.

    PubMed

    Chu, Kar-Hai; Sidhu, Anupreet K; Valente, Thomas W

    2015-01-01

    Electronic cigarette awareness and use has been increasing rapidly. E-cigarette brands have utilized social networking sites to promote their products, as the growth of the e-cigarette industry has paralleled that of Web 2.0. These online platforms are cost-effective and have unique technological features and user demographics that can be attractive for selective marketing. The popularity of multiple sites also poses a risk of exposure to social networks where e-cigarette brands might not have a presence. To examine the marketing strategies of leading e-cigarette brands on multiple social networking sites, and to identify how affordances of the digital media are used to their advantage. Secondary analyses include determining if any brands are benefitting from site demographics, and exploring cross-site diffusion of marketing content through multi-site users. We collected data from two e-cigarette brands from four social networking sites over approximately 2.5 years. Content analysis is used to search for themes, population targeting, marketing strategies, and cross-site spread of messages. Twitter appeared to be the most frequently used social networking site for interacting directly with product users. Facebook supported informational broadcasts, such as announcements regarding political legislation. E-cigarette brands also differed in their approaches to their users, from informal conversations to direct product marketing. E-cigarette makers use different strategies to market their product and engage their users. There was no evidence of direct targeting of vulnerable populations, but the affordances of the different sites are exploited to best broadcast context-specific messages. We developed a viable method to study cross-site diffusion, although additional refinement is needed to account for how different types of digital media are used.

  5. Electronic Cigarette Marketing Online: a Multi-Site, Multi-Product Comparison

    PubMed Central

    Sidhu, Anupreet K; Valente, Thomas W

    2015-01-01

    Background Electronic cigarette awareness and use has been increasing rapidly. E-cigarette brands have utilized social networking sites to promote their products, as the growth of the e-cigarette industry has paralleled that of Web 2.0. These online platforms are cost-effective and have unique technological features and user demographics that can be attractive for selective marketing. The popularity of multiple sites also poses a risk of exposure to social networks where e-cigarette brands might not have a presence. Objective To examine the marketing strategies of leading e-cigarette brands on multiple social networking sites, and to identify how affordances of the digital media are used to their advantage. Secondary analyses include determining if any brands are benefitting from site demographics, and exploring cross-site diffusion of marketing content through multi-site users. Methods We collected data from two e-cigarette brands from four social networking sites over approximately 2.5 years. Content analysis is used to search for themes, population targeting, marketing strategies, and cross-site spread of messages. Results Twitter appeared to be the most frequently used social networking site for interacting directly with product users. Facebook supported informational broadcasts, such as announcements regarding political legislation. E-cigarette brands also differed in their approaches to their users, from informal conversations to direct product marketing. Conclusions E-cigarette makers use different strategies to market their product and engage their users. There was no evidence of direct targeting of vulnerable populations, but the affordances of the different sites are exploited to best broadcast context-specific messages. We developed a viable method to study cross-site diffusion, although additional refinement is needed to account for how different types of digital media are used. PMID:27227129

  6. Creative Entextualizations of Discourses about Race in Multi-Sited Discursive Practices in the Brazilian "Periphery"

    ERIC Educational Resources Information Center

    Guimarães, Thayse Figueira; Moita-Lopes, Luiz Paulo

    2017-01-01

    This paper focuses on Luan's race performances both on the web and in classroom interaction. Luan is a black young man, who identifies himself as gay. The study is part of a multi-sited ethnographic piece of research on a group of high-school students in the state sector, in the "periphery" of a town on the Rio de Janeiro State north…

  7. Development and Applications of Technology for Sensing Zooplankton

    DTIC Science & Technology

    2003-09-30

    zooplankton-like particles. WORK COMPLETED In support of our first objective, in prior years we occupied sites in both East and West Sound at Orcas ...Island in northern Puget Sound , WA. We have also made deployments at four sites on open linear coasts, including one just north of Oceanside, CA (Red...layers. Multi-static, multi-frequency methods Most active bioacoustical methods in oceanography exclusively utilize the sound that is scattered

  8. Potential interoperability problems facing multi-site radiation oncology centers in The Netherlands

    NASA Astrophysics Data System (ADS)

    Scheurleer, J.; Koken, Ph; Wessel, R.

    2014-03-01

    Aim: To identify potential interoperability problems facing multi-site Radiation Oncology (RO) departments in the Netherlands and solutions for unambiguous multi-system workflows. Specific challenges confronting the RO department of VUmc (RO-VUmc), which is soon to open a satellite department, were characterized. Methods: A nationwide questionnaire survey was conducted to identify possible interoperability problems and solutions. Further detailed information was obtained by in-depth interviews at 3 Dutch RO institutes that already operate in more than one site. Results: The survey had a 100% response rate (n=21). Altogether 95 interoperability problems were described. Most reported problems were on a strategic and semantic level. The majority were DICOM(-RT) and HL7 related (n=65), primarily between treatment planning and verification systems or between departmental and hospital systems. Seven were identified as being relevant for RO-VUmc. Departments have overcome interoperability problems with their own, or with tailor-made vendor solutions. There was little knowledge about or utilization of solutions developed by Integrating the Healthcare Enterprise Radiation Oncology (IHE-RO). Conclusions: Although interoperability problems are still common, solutions have been identified. Awareness of IHE-RO needs to be raised. No major new interoperability problems are predicted as RO-VUmc develops into a multi-site department.

  9. Introduction of shared electronic records: multi-site case study using diffusion of innovation theory.

    PubMed

    Greenhalgh, Trisha; Stramer, Katja; Bratan, Tanja; Byrne, Emma; Mohammad, Yara; Russell, Jill

    2008-10-23

    To explore the introduction of a centrally stored, shared electronic patient record (the summary care record (SCR)) in England and draw wider lessons about the implementation of large scale information technology projects in health care. Multi-site, mixed method case study applying utilisation focused evaluation. Four early adopter sites for the SCR in England-three in urban areas of relative socioeconomic deprivation and the fourth in a relatively affluent rural area. Data sources and analysis Data included 250 staff interviews, 1500 hours of ethnographic observation, interviews and focus groups with 170 patients and carers, 2500 pages of correspondence and documentary evidence, and incorporation of relevant surveys and statistics produced by others. These were analysed by using a thematic approach drawing on (and extending) a theoretical model of complex change developed in a previous systematic review. Main findings The mixed fortunes of the SCR programme in its first year were largely explained by eight interacting influences. The first was the SCR's material properties (especially technical immaturity and lack of interoperability) and attributes (especially the extent to which potential adopters believed the benefits outweighed the risks). The second was adopters' concerns (especially about workload and the ethicality of sharing "confidential" information on an implied consent model). The third influence was interpersonal influence (for example, opinion leaders, champions, facilitators), and the fourth was organisational antecedents for innovation (for example past experience with information technology projects, leadership and management capacity, effective data capture systems, slack resources). The fifth was organisational readiness for the SCR (for example, innovation-system fit, tension for change, power balances between supporters and opponents, baseline data quality). The sixth was the implementation process (including the nature of the change model and the extent to which new routines associated with the SCR aligned with existing organisational routines). The seventh influence was the nature and quality of links between different parts of the system, and the final one was the wider environment (especially the political context of the programme). Shared electronic records are not plug-in technologies. They are complex innovations that must be accepted by individual patients and staff and also embedded in organisational and inter-organisational routines. This process is heavily influenced at the micro-level by the material properties of the technology, individuals' attitudes and concerns, and interpersonal influence; at the meso-level by organisational antecedents, readiness, and operational aspects of implementation; and at the macro-level by institutional and socio-political forces. A case study approach and multi-level theoretical analysis can illuminate how contextual factors shape, enable, and constrain new, technology supported models of patient care.

  10. Introduction of shared electronic records: multi-site case study using diffusion of innovation theory

    PubMed Central

    Stramer, Katja; Bratan, Tanja; Byrne, Emma; Mohammad, Yara; Russell, Jill

    2008-01-01

    Objective To explore the introduction of a centrally stored, shared electronic patient record (the summary care record (SCR)) in England and draw wider lessons about the implementation of large scale information technology projects in health care. Design Multi-site, mixed method case study applying utilisation focused evaluation. Setting Four early adopter sites for the SCR in England—three in urban areas of relative socioeconomic deprivation and the fourth in a relatively affluent rural area. Data sources and analysis Data included 250 staff interviews, 1500 hours of ethnographic observation, interviews and focus groups with 170 patients and carers, 2500 pages of correspondence and documentary evidence, and incorporation of relevant surveys and statistics produced by others. These were analysed by using a thematic approach drawing on (and extending) a theoretical model of complex change developed in a previous systematic review. Main findings The mixed fortunes of the SCR programme in its first year were largely explained by eight interacting influences. The first was the SCR’s material properties (especially technical immaturity and lack of interoperability) and attributes (especially the extent to which potential adopters believed the benefits outweighed the risks). The second was adopters’ concerns (especially about workload and the ethicality of sharing “confidential” information on an implied consent model). The third influence was interpersonal influence (for example, opinion leaders, champions, facilitators), and the fourth was organisational antecedents for innovation (for example past experience with information technology projects, leadership and management capacity, effective data capture systems, slack resources). The fifth was organisational readiness for the SCR (for example, innovation-system fit, tension for change, power balances between supporters and opponents, baseline data quality). The sixth was the implementation process (including the nature of the change model and the extent to which new routines associated with the SCR aligned with existing organisational routines). The seventh influence was the nature and quality of links between different parts of the system, and the final one was the wider environment (especially the political context of the programme). Conclusion Shared electronic records are not plug-in technologies. They are complex innovations that must be accepted by individual patients and staff and also embedded in organisational and inter-organisational routines. This process is heavily influenced at the micro-level by the material properties of the technology, individuals’ attitudes and concerns, and interpersonal influence; at the meso-level by organisational antecedents, readiness, and operational aspects of implementation; and at the macro-level by institutional and socio-political forces. A case study approach and multi-level theoretical analysis can illuminate how contextual factors shape, enable, and constrain new, technology supported models of patient care. PMID:18948344

  11. The geologic setting of the Luna 16 landing site

    USGS Publications Warehouse

    McCauley, J.F.; Scott, D.H.

    1972-01-01

    The Luna 16 landing site is similar in its geologic setting to Apollos 11 and 12. All three sites are located on basaltic mare fill which occurs mostly within multi-ring basins formed by impact earlier in the moon's history. A regolith developed by impact bombardment is present at each of these sites. The regolith is composed mostly of locally derived volcanic material, but also contains exotic fine fragments that have been ballistically transported into the landing sites by large impact events which formed craters such as Langrenus and Copernicus. These exotic fragments probably consist mostly of earlier reworked multi-ring basin debris and, although not directly traceable to individual sources, they do represent a good statistical sample of the composition of most of the premare terrac regions. ?? 1972.

  12. Lessons learned from a practice-based, multi-site intervention study with nurse participants

    PubMed Central

    Friese, Christopher R.; Mendelsohn-Victor, Kari; Ginex, Pamela; McMahon, Carol M.; Fauer, Alex J.; McCullagh, Marjorie C.

    2016-01-01

    Purpose To identify challenges and solutions to the efficient conduct of a multi-site, practice-based randomized controlled trial to improve nurses’ adherence to personal protective equipment use in ambulatory oncology settings. Design The Drug Exposure Feedback and Education for Nurses’ Safety (DEFENS) study is a clustered, randomized, controlled trial. Participating sites are randomized to web-based feedback on hazardous drug exposures in the sites plus tailored messages to address barriers versus a control intervention of a web-based continuing education video. Approach The study principal investigator, the study coordinator, and two site leaders identified challenges to study implementation and potential solutions, plus potential methods to prevent logistical challenges in future studies. Findings Noteworthy challenges included variation in human subjects protection policies, grants and contracts budgeting, infrastructure for nursing-led research, and information technology variation. Successful strategies included scheduled web conferences, site-based study champions, site visits by the principal investigator, and centrally-based document preparation. Strategies to improve efficiency in future studies include early and continued engagement with contract personnel in sites, and proposed changes to the common rule concerning human subjects. The DEFENS study successfully recruited 393 nurses across 12 sites. To date, 369 have completed surveys and 174 nurses have viewed educational materials. Conclusions Multi-site studies of nursing personnel are rare and challenging to existing infrastructure. These barriers can be overcome with strong engagement and planning. Clinical Relevance Leadership engagement, onsite staff support, and continuous communication can facilitate successful recruitment to a workplace-based randomized, controlled behavioral trial. PMID:28098951

  13. Globalisation, Mergers and "Inadvertent Multi-Campus Universities": Reflections from Wales

    ERIC Educational Resources Information Center

    Zeeman, Nadine; Benneworth, Paul

    2017-01-01

    Multi-site universities face the challenge of integrating campuses that may have different profiles and orientations arising from place-specific attachments. Multi-campus universities created via mergers seeking to ensure long-term financial sustainability, and increasing their attractiveness to students, create a tension in campuses' purposes. We…

  14. PDT-based combinations in overcoming chemoresistance from stromal and heterotypic cellular communication (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Rizvi, Imran; Bulin, Anne-Laure; Anbil, Sriram R.; Briars, Emma A.; Vecchio, Daniela; Celli, Jonathan P.; Broekgaarden, Mans; Hasan, Tayyaba

    2017-02-01

    Targeting the molecular and cellular cues that influence treatment resistance in tumors is critical to effectively treating unresponsive populations of stubborn disease. The informed design of mechanism-based combinations is emerging as increasingly important to targeting resistance and improving the efficacy of conventional treatments, while minimizing toxicity. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Increasing evidence shows that PDT-based combinations cooperate mechanistically with, and improve the therapeutic index of, traditional chemotherapies. These and other findings emphasize the importance of including PDT as part of comprehensive treatment plans for cancer, particularly in complex disease sites. Identifying effective combinations requires a multi-faceted approach that includes the development of bioengineered cancer models and corresponding image analysis tools. The molecular and phenotypic basis of verteporfin-mediated PDT-based enhancement of chemotherapeutic efficacy and predictability in complex 3D models for ovarian cancer will be presented.

  15. Near-atomic resolution visualization of human transcription promoter opening

    PubMed Central

    He, Yuan; Yan, Chunli; Fang, Jie; Inouye, Carla; Tjian, Robert; Ivanov, Ivaylo; Nogales, Eva

    2016-01-01

    In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA–RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB. PMID:27193682

  16. Tier-2 Optimisation for Computational Density/Diversity and Big Data

    NASA Astrophysics Data System (ADS)

    Fay, R. B.; Bland, J.

    2014-06-01

    As the number of cores on chip continues to trend upwards and new CPU architectures emerge, increasing CPU density and diversity presents multiple challenges to site administrators. These include scheduling for massively multi-core systems (potentially including Graphical Processing Units (GPU), integrated and dedicated) and Many Integrated Core (MIC)) to ensure a balanced throughput of jobs while preserving overall cluster throughput, as well as the increasing complexity of developing for these heterogeneous platforms, and the challenge in managing this more complex mix of resources. In addition, meeting data demands as both dataset sizes increase and as the rate of demand scales with increased computational power requires additional performance from the associated storage elements. In this report, we evaluate one emerging technology, Solid State Drive (SSD) caching for RAID controllers, with consideration to its potential to assist in meeting evolving demand. We also briefly consider the broader developing trends outlined above in order to identify issues that may develop and assess what actions should be taken in the immediate term to address those.

  17. A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions

    PubMed Central

    Wolfenson, Haguy; Lubelski, Ariel; Regev, Tamar; Klafter, Joseph; Henis, Yoav I.; Geiger, Benjamin

    2009-01-01

    Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization. PMID:19172999

  18. Global Optimization of Low-Thrust Interplanetary Trajectories Subject to Operational Constraints

    NASA Technical Reports Server (NTRS)

    Englander, Jacob A.; Vavrina, Matthew A.; Hinckley, David

    2016-01-01

    Low-thrust interplanetary space missions are highly complex and there can be many locally optimal solutions. While several techniques exist to search for globally optimal solutions to low-thrust trajectory design problems, they are typically limited to unconstrained trajectories. The operational design community in turn has largely avoided using such techniques and has primarily focused on accurate constrained local optimization combined with grid searches and intuitive design processes at the expense of efficient exploration of the global design space. This work is an attempt to bridge the gap between the global optimization and operational design communities by presenting a mathematical framework for global optimization of low-thrust trajectories subject to complex constraints including the targeting of planetary landing sites, a solar range constraint to simplify the thermal design of the spacecraft, and a real-world multi-thruster electric propulsion system that must switch thrusters on and off as available power changes over the course of a mission.

  19. Using multi-criteria analysis of simulation models to understand complex biological systems

    Treesearch

    Maureen C. Kennedy; E. David Ford

    2011-01-01

    Scientists frequently use computer-simulation models to help solve complex biological problems. Typically, such models are highly integrated, they produce multiple outputs, and standard methods of model analysis are ill suited for evaluating them. We show how multi-criteria optimization with Pareto optimality allows for model outputs to be compared to multiple system...

  20. Emerging Challenges and Opportunities for Education and Research in Weed Science

    PubMed Central

    Chauhan, Bhagirath S.; Matloob, Amar; Mahajan, Gulshan; Aslam, Farhena; Florentine, Singarayer K.; Jha, Prashant

    2017-01-01

    In modern agriculture, with more emphasis on high input systems, weed problems are likely to increase and become more complex. With heightened awareness of adverse effects of herbicide residues on human health and environment and the evolution of herbicide-resistant weed biotypes, a significant focus within weed science has now shifted to the development of eco-friendly technologies with reduced reliance on herbicides. Further, with the large-scale adoption of herbicide-resistant crops, and uncertain climatic optima under climate change, the problems for weed science have become multi-faceted. To handle these complex weed problems, a holistic line of action with multi-disciplinary approaches is required, including adjustments to technology, management practices, and legislation. Improved knowledge of weed ecology, biology, genetics, and molecular biology is essential for developing sustainable weed control practices. Additionally, judicious use of advanced technologies, such as site-specific weed management systems and decision support modeling, will play a significant role in reducing costs associated with weed control. Further, effective linkages between farmers and weed researchers will be necessary to facilitate the adoption of technological developments. To meet these challenges, priorities in research need to be determined and the education system for weed science needs to be reoriented. In respect of the latter imperative, closer collaboration between weed scientists and other disciplines can help in defining and solving the complex weed management challenges of the 21st century. This consensus will provide more versatile and diverse approaches to innovative teaching and training practices, which will be needed to prepare future weed science graduates who are capable of handling the anticipated challenges of weed science facing in contemporary agriculture. To build this capacity, mobilizing additional funding for both weed research and weed management education is essential. PMID:28928765

  1. Emerging Challenges and Opportunities for Education and Research in Weed Science.

    PubMed

    Chauhan, Bhagirath S; Matloob, Amar; Mahajan, Gulshan; Aslam, Farhena; Florentine, Singarayer K; Jha, Prashant

    2017-01-01

    In modern agriculture, with more emphasis on high input systems, weed problems are likely to increase and become more complex. With heightened awareness of adverse effects of herbicide residues on human health and environment and the evolution of herbicide-resistant weed biotypes, a significant focus within weed science has now shifted to the development of eco-friendly technologies with reduced reliance on herbicides. Further, with the large-scale adoption of herbicide-resistant crops, and uncertain climatic optima under climate change, the problems for weed science have become multi-faceted. To handle these complex weed problems, a holistic line of action with multi-disciplinary approaches is required, including adjustments to technology, management practices, and legislation. Improved knowledge of weed ecology, biology, genetics, and molecular biology is essential for developing sustainable weed control practices. Additionally, judicious use of advanced technologies, such as site-specific weed management systems and decision support modeling, will play a significant role in reducing costs associated with weed control. Further, effective linkages between farmers and weed researchers will be necessary to facilitate the adoption of technological developments. To meet these challenges, priorities in research need to be determined and the education system for weed science needs to be reoriented. In respect of the latter imperative, closer collaboration between weed scientists and other disciplines can help in defining and solving the complex weed management challenges of the 21st century. This consensus will provide more versatile and diverse approaches to innovative teaching and training practices, which will be needed to prepare future weed science graduates who are capable of handling the anticipated challenges of weed science facing in contemporary agriculture. To build this capacity, mobilizing additional funding for both weed research and weed management education is essential.

  2. Species diversity in the marine microturbellarian Astrotorhynchus bifidus sensu lato (Platyhelminthes: Rhabdocoela) from the Northeast Pacific Ocean.

    PubMed

    Van Steenkiste, Niels W L; Herbert, Elizabeth R; Leander, Brian S

    2018-03-01

    Increasing evidence suggests that many widespread species of meiofauna are in fact regional complexes of (pseudo-)cryptic species. This knowledge has challenged the 'Everything is Everywhere' hypothesis and also partly explains the meiofauna paradox of widespread nominal species with limited dispersal abilities. Here, we investigated species diversity within the marine microturbellarian Astrotorhynchus bifidus sensu lato in the Northeast Pacific Ocean. We used a multiple-evidence approach combining multi-gene (18S, 28S, COI) phylogenetic analyses, several single-gene and multi-gene species delimitation methods, haplotype networks and conventional taxonomy to designate Primary Species Hypotheses (PSHs). This included the development of rhabdocoel-specific COI barcode primers, which also have the potential to aid in species identification and delimitation in other rhabdocoels. Secondary Species Hypotheses (SSHs) corresponding to morphospecies and pseudo-cryptic species were then proposed based on the minimum consensus of different PSHs. Our results showed that (a) there are at least five species in the A. bifidus complex in the Northeast Pacific Ocean, four of which can be diagnosed based on stylet morphology, (b) the A. bifidus complex is a mixture of sympatric and allopatric species with regional and/or subglobal distributions, (c) sympatry occurs on local (sample sites), regional (Northeastern Pacific) and subglobal (Northern Atlantic, Arctic, Northeastern Pacific) scales. Mechanisms for this co-occurrence are still poorly understood, but we hypothesize they could include habitat differentiation (spatial and/or seasonal) and life history characteristics such as sexual selection and dispersal abilities. Our results also suggest the need for improved sampling and exploration of molecular markers to accurately map gene flow and broaden our understanding of species diversity and distribution of microturbellarians in particular and meiofauna in general. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Multi-segmental movement patterns reflect juggling complexity and skill level.

    PubMed

    Zago, Matteo; Pacifici, Ilaria; Lovecchio, Nicola; Galli, Manuela; Federolf, Peter Andreas; Sforza, Chiarella

    2017-08-01

    The juggling action of six experts and six intermediates jugglers was recorded with a motion capture system and decomposed into its fundamental components through Principal Component Analysis. The aim was to quantify trends in movement dimensionality, multi-segmental patterns and rhythmicity as a function of proficiency level and task complexity. Dimensionality was quantified in terms of Residual Variance, while the Relative Amplitude was introduced to account for individual differences in movement components. We observed that: experience-related modifications in multi-segmental actions exist, such as the progressive reduction of error-correction movements, especially in complex task condition. The systematic identification of motor patterns sensitive to the acquisition of specific experience could accelerate the learning process. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Application of Layered Perforation Profile Control Technique to Low Permeable Reservoir

    NASA Astrophysics Data System (ADS)

    Wei, Sun

    2018-01-01

    it is difficult to satisfy the demand of profile control of complex well section and multi-layer reservoir by adopting the conventional profile control technology, therefore, a research is conducted on adjusting the injection production profile with layered perforating parameters optimization. i.e. in the case of coproduction for multi-layer, water absorption of each layer is adjusted by adjusting the perforating parameters, thus to balance the injection production profile of the whole well section, and ultimately enhance the oil displacement efficiency of water flooding. By applying the relationship between oil-water phase percolation theory/perforating damage and capacity, a mathematic model of adjusting the injection production profile with layered perforating parameters optimization, besides, perforating parameters optimization software is programmed. Different types of optimization design work are carried out according to different geological conditions and construction purposes by using the perforating optimization design software; furthermore, an application test is done for low permeable reservoir, and the water injection profile tends to be balanced significantly after perforation with optimized parameters, thereby getting a good application effect on site.

  5. A genetically optimized kinetic model for ethanol electro-oxidation on Pt-based binary catalysts used in direct ethanol fuel cells

    NASA Astrophysics Data System (ADS)

    Sánchez-Monreal, Juan; García-Salaberri, Pablo A.; Vera, Marcos

    2017-09-01

    A one-dimensional model is proposed for the anode of a liquid-feed direct ethanol fuel cell. The complex kinetics of the ethanol electro-oxidation reaction is described using a multi-step reaction mechanism that considers free and adsorbed intermediate species on Pt-based binary catalysts. The adsorbed species are modeled using coverage factors to account for the blockage of the active reaction sites on the catalyst surface. The reaction rates are described by Butler-Volmer equations that are coupled to a one-dimensional mass transport model, which incorporates the effect of ethanol and acetaldehyde crossover. The proposed kinetic model circumvents the acetaldehyde bottleneck effect observed in previous studies by incorporating CH3CHOHads among the adsorbed intermediates. A multi-objetive genetic algorithm is used to determine the reaction constants using anode polarization and product selectivity data obtained from the literature. By adjusting the reaction constants using the methodology developed here, different catalyst layers could be modeled and their selectivities could be successfully reproduced.

  6. Simultaneous determination of nandrolone, testosterone, and methyltestosterone by multi-immunoaffinity column and capillary electrophoresis.

    PubMed

    Qi, Xiao-Hua; Zhang, Li-Wei; Zhang, Xin-Xiang

    2008-08-01

    A multitarget antibody immunoaffinity column was proposed for the purification and enrichment of nandrolone, testosterone, and methyltestosterone from urine. Nandrolone-3-site substituted antigen was designed and synthesized and the polyclonal antibody was prepared with immunizing rabbits. The stationary phase of the immunoaffinity column was synthesized by covalently bonding the antibodies specific to nandrolone, testosterone, and methyltestosterone onto CNBr-actived Sepharose 4B. The analytes of interest were extracted with a methanol/water mixture in one step. The immunoaffinity column showed high affinity and high selectivity to a class of structurally related compounds. The elution was then transferred to a micellar electrokinetic CE system with a running buffer of sodium borate and sodium cholate for separation and determination. Recoveries of the three steroids from complex matrix were 88-94% with RSD values less than 5.2%. Optimization of the immunoaffinity column purification was achieved and the feasibility of the technique for the analysis of steroid hormone was discussed. The results indicated that the combination of multi-immunoaffinity column and CE was an effective technique, which was rapid, simple, and sensitive for the assay of steroids.

  7. Application of pulsed multi-ion irradiations in radiation damage research: A stochastic cluster dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Hoang, Tuan L.; Nazarov, Roman; Kang, Changwoo; Fan, Jiangyuan

    2018-07-01

    Under the multi-ion irradiation conditions present in accelerated material-testing facilities or fission/fusion nuclear reactors, the combined effects of atomic displacements with radiation products may induce complex synergies in the structural materials. However, limited access to multi-ion irradiation facilities and the lack of computational models capable of simulating the evolution of complex defects and their synergies make it difficult to understand the actual physical processes taking place in the materials under these extreme conditions. In this paper, we propose the application of pulsed single/dual-beam irradiation as replacements for the expensive steady triple-beam irradiation to study radiation damages in materials under multi-ion irradiation.

  8. Using Systems Thinking to train future leaders in global health.

    PubMed

    Paxton, Anne; Frost, Laura J

    2017-07-09

    Systems Thinking provides a useful set of concepts and tools that can be used to train students to be effective and innovative global health leaders in an ever-changing and often chaotic world. This paper describes an experiential, multi-disciplinary curriculum that uses Systems Thinking to frame and analyse global health policies and practices. The curriculum uses case studies and hands-on activities to deepen students' understanding of the following concepts: complex adaptive systems, dynamic complexity, inter-relationships, feedback loops, policy resistance, mental models, boundary critique, leverage points, and multi-disciplinary, multi-sectoral, and multi-stakeholder thinking and action. A sample of Systems Thinking tools for analysing global health policies and practices are also introduced.

  9. Multi-enzyme logic network architectures for assessing injuries: digital processing of biomarkers.

    PubMed

    Halámek, Jan; Bocharova, Vera; Chinnapareddy, Soujanya; Windmiller, Joshua Ray; Strack, Guinevere; Chuang, Min-Chieh; Zhou, Jian; Santhosh, Padmanabhan; Ramirez, Gabriela V; Arugula, Mary A; Wang, Joseph; Katz, Evgeny

    2010-12-01

    A multi-enzyme biocatalytic cascade processing simultaneously five biomarkers characteristic of traumatic brain injury (TBI) and soft tissue injury (STI) was developed. The system operates as a digital biosensor based on concerted function of 8 Boolean AND logic gates, resulting in the decision about the physiological conditions based on the logic analysis of complex patterns of the biomarkers. The system represents the first example of a multi-step/multi-enzyme biosensor with the built-in logic for the analysis of complex combinations of biochemical inputs. The approach is based on recent advances in enzyme-based biocomputing systems and the present paper demonstrates the potential applicability of biocomputing for developing novel digital biosensor networks.

  10. Coarse-Grained Molecular Simulation of Epidermal Growth Factor Receptor Protein Tyrosine Kinase Multi-Site Self-Phosphorylation

    PubMed Central

    Koland, John G.

    2014-01-01

    Upon the ligand-dependent dimerization of the epidermal growth factor receptor (EGFR), the intrinsic protein tyrosine kinase (PTK) activity of one receptor monomer is activated, and the dimeric receptor undergoes self-phosphorylation at any of eight candidate phosphorylation sites (P-sites) in either of the two C-terminal (CT) domains. While the structures of the extracellular ligand binding and intracellular PTK domains are known, that of the ∼225-amino acid CT domain is not, presumably because it is disordered. Receptor phosphorylation on CT domain P-sites is critical in signaling because of the binding of specific signaling effector molecules to individual phosphorylated P-sites. To investigate how the combination of conventional substrate recognition and the unique topological factors involved in the CT domain self-phosphorylation reaction lead to selectivity in P-site phosphorylation, we performed coarse-grained molecular simulations of the P-site/catalytic site binding reactions that precede EGFR self-phosphorylation events. Our results indicate that self-phosphorylation of the dimeric EGFR, although generally believed to occur in trans, may well occur with a similar efficiency in cis, with the P-sites of both receptor monomers being phosphorylated to a similar extent. An exception was the case of the most kinase-proximal P-site-992, the catalytic site binding of which occurred exclusively in cis via an intramolecular reaction. We discovered that the in cis interaction of P-site-992 with the catalytic site was facilitated by a cleft between the N-terminal and C-terminal lobes of the PTK domain that allows the short CT domain sequence tethering P-site-992 to the PTK core to reach the catalytic site. Our work provides several new mechanistic insights into the EGFR self-phosphorylation reaction, and demonstrates the potential of coarse-grained molecular simulation approaches for investigating the complexities of self-phosphorylation in molecules such as EGFR (HER/ErbB) family receptors and growth factor receptor PTKs in general. PMID:24453959

  11. Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask

    PubMed Central

    Scheldrup, Melissa; Greenwood, Pamela M.; McKendrick, Ryan; Strohl, Jon; Bikson, Marom; Alam, Mahtab; McKinley, R. Andy; Parasuraman, Raja

    2014-01-01

    There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation—specifically transcranial Direct Current Stimulation (tDCS)—has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical. PMID:25249958

  12. Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

    PubMed

    Scheldrup, Melissa; Greenwood, Pamela M; McKendrick, Ryan; Strohl, Jon; Bikson, Marom; Alam, Mahtab; McKinley, R Andy; Parasuraman, Raja

    2014-01-01

    There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation-specifically transcranial Direct Current Stimulation (tDCS)-has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

  13. Identifying strategic sites for Green-Infrastructures (GI) to manage stormwater in a miscellaneous use urban African watershed

    NASA Astrophysics Data System (ADS)

    Selker, J. S.; Kahsai, S. K.

    2017-12-01

    Green Infrastructure (GI) or Low impact development (LID), is a land use planning and design approach with the objective of mitigating land development impacts to the environment, and is ever more looked to as a way to lessen runoff and pollutant loading to receiving water bodies. Broad-scale approaches for siting GI/LID have been developed for agricultural watersheds, but are rare for urban watersheds, largely due to greater land use complexity. And it is even more challenging when it comes to Urban Africa due to the combination of poor data quality, rapid and unplanned development, and civic institutions unable to reliably carry out regular maintenance. We present a spacio-temporal simulation-based approach to identify an optimal prioritization of sites for GI/LID based on DEM, land use and land cover. Optimization used is a multi-objective optimization tool along with an urban storm water management model (SWMM) to identify the most cost-effective combination of LID/GI. This was applied to an urban watershed in NW Kampala, Lubigi Catchment (notorious for being heavily flooded every year), with a miscellaneous use watershed in Uganda, as a case-study to demonstrate the approach.

  14. Ten Steps to Conducting a Large, Multi-Site, Longitudinal Investigation of Language and Reading in Young Children

    PubMed Central

    Farquharson, Kelly; Murphy, Kimberly A.

    2016-01-01

    Purpose: This paper describes methodological procedures involving execution of a large-scale, multi-site longitudinal study of language and reading comprehension in young children. Researchers in the Language and Reading Research Consortium (LARRC) developed and implemented these procedures to ensure data integrity across multiple sites, schools, and grades. Specifically, major features of our approach, as well as lessons learned, are summarized in 10 steps essential for successful completion of a large-scale longitudinal investigation in early grades. Method: Over 5 years, children in preschool through third grade were administered a battery of 35 higher- and lower-level language, listening, and reading comprehension measures (RCM). Data were collected from children, their teachers, and their parents/guardians at four sites across the United States. Substantial and rigorous effort was aimed toward maintaining consistency in processes and data management across sites for children, assessors, and staff. Conclusion: With appropriate planning, flexibility, and communication strategies in place, LARRC developed and executed a successful multi-site longitudinal research study that will meet its goal of investigating the contribution and role of language skills in the development of children's listening and reading comprehension. Through dissemination of our design strategies and lessons learned, research teams embarking on similar endeavors can be better equipped to anticipate the challenges. PMID:27064308

  15. Site Map | USDA Plant Hardiness Zone Map

    Science.gov Websites

    Acknowledgments & Citation Copyright Map & Data Downloads Map Downloads Geography (GIS) Downloads Multi ; Citation Copyright Map & Data Downloads Map Downloads Geography (GIS) Downloads Multi-ZIP Code Finder

  16. The role of economics in the QUERI program: QUERI Series

    PubMed Central

    Smith, Mark W; Barnett, Paul G

    2008-01-01

    Background The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. Methods We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Results Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Conclusion Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics. PMID:18430199

  17. The role of economics in the QUERI program: QUERI Series.

    PubMed

    Smith, Mark W; Barnett, Paul G

    2008-04-22

    The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics.

  18. Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Chi, Gloria C; Liu, Yongmei; MacDonald, James W; Barr, R Graham; Donohue, Kathleen M; Hensley, Mark D; Hou, Lifang; McCall, Charles E; Reynolds, Lindsay M; Siscovick, David S; Kaufman, Joel D

    2016-12-01

    DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). One-year average ambient fine particulate matter (PM 2.5 ) and oxides of nitrogen (NO X ) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM 2.5 and none were associated with NO X . Cg20455854 had the smallest p-value for the association with PM 2.5 (p = 2.77 × 10 -5 ). mRNA expression profiles of genes near three of the PM 2.5 -associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM 2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.

  19. Recording Approach of Heritage Sites Based on Merging Point Clouds from High Resolution Photogrammetry and Terrestrial Laser Scanning

    NASA Astrophysics Data System (ADS)

    Grussenmeyer, P.; Alby, E.; Landes, T.; Koehl, M.; Guillemin, S.; Hullo, J. F.; Assali, P.; Smigiel, E.

    2012-07-01

    Different approaches and tools are required in Cultural Heritage Documentation to deal with the complexity of monuments and sites. The documentation process has strongly changed in the last few years, always driven by technology. Accurate documentation is closely relied to advances of technology (imaging sensors, high speed scanning, automation in recording and processing data) for the purposes of conservation works, management, appraisal, assessment of the structural condition, archiving, publication and research (Patias et al., 2008). We want to focus in this paper on the recording aspects of cultural heritage documentation, especially the generation of geometric and photorealistic 3D models for accurate reconstruction and visualization purposes. The selected approaches are based on the combination of photogrammetric dense matching and Terrestrial Laser Scanning (TLS) techniques. Both techniques have pros and cons and recent advances have changed the way of the recording approach. The choice of the best workflow relies on the site configuration, the performances of the sensors, and criteria as geometry, accuracy, resolution, georeferencing, texture, and of course processing time. TLS techniques (time of flight or phase shift systems) are widely used for recording large and complex objects and sites. Point cloud generation from images by dense stereo or multi-view matching can be used as an alternative or as a complementary method to TLS. Compared to TLS, the photogrammetric solution is a low cost one, as the acquisition system is limited to a high-performance digital camera and a few accessories only. Indeed, the stereo or multi-view matching process offers a cheap, flexible and accurate solution to get 3D point clouds. Moreover, the captured images might also be used for models texturing. Several software packages are available, whether web-based, open source or commercial. The main advantage of this photogrammetric or computer vision based technology is to get at the same time a point cloud (the resolution depends on the size of the pixel on the object), and therefore an accurate meshed object with its texture. After matching and processing steps, we can use the resulting data in much the same way as a TLS point cloud, but in addition with radiometric information for textures. The discussion in this paper reviews recording and important processing steps as geo-referencing and data merging, the essential assessment of the results, and examples of deliverables from projects of the Photogrammetry and Geomatics Group (INSA Strasbourg, France).

  20. A multi-biomarker approach in cross-transplanted mussels Mytilus galloprovincialis.

    PubMed

    Serafim, Angela; Lopes, Belisandra; Company, Rui; Cravo, Alexandra; Gomes, Tânia; Sousa, Vânia; Bebianno, Maria João

    2011-11-01

    The present work integrates the active biomonitoring (ABM) concept in mussels Mytilus galloprovincialis from the South coast of Portugal transplanted during 28 days between two sites with different sources of contamination, and vice versa, in order to assess biological effects in these mussels. For that purpose a multibiomarker approach was used. The suit of biomarkers indicative of metal contamination were metallothioneins (MT) and the enzyme δ-aminolevulinic acid dehydratase (ALAD), for organic contamination mixed function oxidase system (MFO), glutathione-S-transferase (GST) and acetylcholinesterase (AChE), as oxidative stress biomarkers superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (LPO). These biomarkers were used to determine an index to evaluate the stress levels in these two sites. Site A is strongly influenced by metallic contamination, with higher Cu, Cr and Pb in M. galloprovincialis, as well as higher MT levels, antioxidant enzymes activities and LPO concentrations, and lower ALAD activity. In site B organic compounds (PAHs) are prevalent and native mussels show higher activities of the MFO system components and GST. Transplanted mussels had significant alterations in some biomarkers that reflect the type of contaminants present in each site, which demonstrates the primary role of the environment in determining the physiological characteristics of resident mussels. Therefore the application of ABM using a battery of biomarkers turns out to be a useful approach in sites where usually complex mixtures of contaminants occurs. In this study the biomarkers that better differentiate the impact of different contaminants at each site were MT, CYP450, SOD and CAT.

  1. BASIN-SCALE ASSESSMENTS FOR SUSTAINABLE ECOSYSTEMS (BASE)

    EPA Science Inventory

    The need for multi-media, multi-stressor, and multi-response models for ecological assessment is widely acknowledged. Assessments at this level of complexity have not been conducted, and therefore pilot assessments are required to identify the critical concepts, models, data, and...

  2. Use of focus groups in multi-site, multi-ethnic research projects for women's health: a Study of Women Across the Nation (swan) example.

    PubMed

    Kagawa-Singer, Marjorie; Adler, Shelley R; Mouton, Charles E; Ory, Marcia; Underwood, Lynne G

    2009-01-01

    To outline the lessons learned about the use of focus groups for the multisite, multi-ethnic longitudinal Study of Women Across the Nation (SWAN). Focus groups were designed to identify potential cultural differences in the incidence of symptoms and the meaning of transmenopause among women of diverse cultures, and to identify effective recruitment and retention strategies. Inductive and deductive focus groups for a multi-ethnic study. Seven community research sites across the United States conducted focus groups with six ethnic populations: African American, Chinese American, Japanese American, Mexican American, non-Hispanic white, and Puerto Rican. Community women from each ethnic group of color. A set of four/five focus groups in each ethnic group as the formative stage of the deductive, quantitative SWAN survey. Identification of methodological advantages and challenges to the successful implementation of formative focus groups in a multi-ethnic, multi-site population-based epidemiologic study. We provide recommendations from our lessons learned to improve the use of focus groups in future studies with multi-ethnic populations. Mixed methods using inductive and deductive approaches require the scientific integrity of both research paradigms. Adequate resources and time must be budgeted as essential parts of the overall strategy from the outset of study. Inductive cross-cultural researchers should be key team members, beginning with inception through each subsequent design phase to increase the scientific validity, generalizability, and comparability of the results across diverse ethnic groups, to assure the relevance, validity and applicability of the findings to the multicultural population of focus.

  3. Cwf16p Associating with the Nineteen Complex Ensures Ordered Exon Joining in Constitutive Pre-mRNA Splicing in Fission Yeast

    PubMed Central

    Sasaki-Haraguchi, Noriko; Ikuyama, Takeshi; Yoshii, Shogo; Takeuchi-Andoh, Tomoko; Frendewey, David; Tani, Tokio

    2015-01-01

    Exons are ligated in an ordered manner without the skipping of exons in the constitutive splicing of pre-mRNAs with multiple introns. To identify factors ensuring ordered exon joining in constitutive pre-mRNA splicing, we previously screened for exon skipping mutants in Schizosaccharomyces pombe using a reporter plasmid, and characterized three exon skipping mutants named ods1 (ordered splicing 1), ods2, and ods3, the responsible genes of which encode Prp2/U2AF59, U2AF23, and SF1, respectively. They form an SF1-U2AF59-U2AF23 complex involved in recognition of the branch and 3′ splice sites in pre-mRNA. In the present study, we identified a fourth ods mutant, ods4, which was isolated in an exon-skipping screen. The ods4 + gene encodes Cwf16p, which interacts with the NineTeen Complex (NTC), a complex thought to be involved in the first catalytic step of the splicing reaction. We isolated two multi-copy suppressors for the ods4-1 mutation, Srp2p, an SR protein essential for pre-mRNA splicing, and Tif213p, a translation initiation factor, in S. pombe. The overexpression of Srp2p suppressed the exon-skipping phenotype of all ods mutants, whereas Tif213p suppressed only ods4-1, which has a mutation in the translational start codon of the cwf16 gene. We also showed that the decrease in the transcriptional elongation rate induced by drug treatment suppressed exon skipping in ods4-1. We propose that Cwf16p/NTC participates in the early recognition of the branch and 3′ splice sites and cooperates with the SF1-U2AF59-U2AF23 complex to maintain ordered exon joining. PMID:26302002

  4. Binding interaction of ramipril with bovine serum albumin (BSA): Insights from multi-spectroscopy and molecular docking methods.

    PubMed

    Shi, Jie-Hua; Pan, Dong-Qi; Jiang, Min; Liu, Ting-Ting; Wang, Qi

    2016-11-01

    The binding interaction between a typical angiotensin-converting enzyme inhibitor (ACEI), ramipril, and a transport protein, bovine serum albumin (BSA), was studied in vitro using UV-vis absorption spectroscopy, steady-state fluorescence spectroscopic titration, synchronous fluorescence spectroscopy, three dimensional fluorescence spectroscopy, circular dichroism and molecular docking under the imitated physiological conditions (pH=7.4). The experimental results suggested that the intrinsic fluorescence of BSA was quenched by ramipril thought a static quenching mechanism, indicating that the stable ramipril-BSA complex was formed by the intermolecular interaction. The number of binding sites (n) and binding constant of ramipril-BSA complex were about 1 and 3.50×10 4 M -1 at 298K, respectively, suggesting that there was stronger binding interaction of ramipril with BSA. The thermodynamic parameters together with molecular docking study revealed that both van der Waal's forces and hydrogen bonding interaction dominated the formation of the ramipril-BSA complex and the binding interaction of BSA with ramipril is enthalpy-driven processes due to |ΔH°|>|TΔS°| and ΔG°<0. The spatial distance between ramipril and BSA was calculated to be 3.56nm based on Förster's non-radiative energy transfer theory. The results of the competitive displacement experiments and molecular docking confirmed that ramipril inserted into the subdomain IIA (site I) of BSA, resulting in a slight change in the conformation of BSA but BSA still retained its secondary structure α-helicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin-dependent membrane organizing proteins.

    PubMed

    Serricchio, Mauro; Vissa, Adriano; Kim, Peter K; Yip, Christopher M; McQuibban, G Angus

    2018-04-01

    The mitochondrial glycerophospholipid cardiolipin plays important roles in mitochondrial biology. Most notably, cardiolipin directly binds to mitochondrial proteins and helps assemble and stabilize mitochondrial multi-protein complexes. Despite their importance for mitochondrial health, how the proteins involved in cardiolipin biosynthesis are organized and embedded in mitochondrial membranes has not been investigated in detail. Here we show that human PGS1 and CLS1 are constituents of large protein complexes. We show that PGS1 forms oligomers and associates with CLS1 and PTPMT1. Using super-resolution microscopy, we observed well-organized nanoscale structures formed by PGS1. Together with the observation that cardiolipin and CLS1 are not required for PGS1 to assemble in the complex we predict the presence of a PGS1-centered cardiolipin-synthesizing scaffold within the mitochondrial inner membrane. Using an unbiased proteomic approach we found that PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS components MIC60 and MIC19. We further mapped the protein-protein interaction sites between PGS1 and itself, CLS1, MIC60 and PHB. Overall, this study provides evidence for the presence of a cardiolipin synthesis structure that transiently interacts with cardiolipin-dependent protein complexes. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. A multiscale analysis of coral reef topographic complexity using lidar-derived bathymetry

    USGS Publications Warehouse

    Zawada, D.G.; Brock, J.C.

    2009-01-01

    Coral reefs represent one of the most irregular substrates in the marine environment. This roughness or topographic complexity is an important structural characteristic of reef habitats that affects a number of ecological and environmental attributes, including species diversity and water circulation. Little is known about the range of topographic complexity exhibited within a reef or between different reef systems. The objective of this study was to quantify topographic complexity for a 5-km x 5-km reefscape along the northern Florida Keys reef tract, over spatial scales ranging from meters to hundreds of meters. The underlying dataset was a 1-m spatial resolution, digital elevation model constructed from lidar measurements. Topographic complexity was quantified using a fractal algorithm, which provided a multi-scale characterization of reef roughness. The computed fractal dimensions (D) are a measure of substrate irregularity and are bounded between values of 2 and 3. Spatial patterns in D were positively correlated with known reef zonation in the area. Landward regions of the study site contain relatively smooth (D ??? 2.35) flat-topped patch reefs, which give way to rougher (D ??? 2.5), deep, knoll-shaped patch reefs. The seaward boundary contains a mixture of substrate features, including discontinuous shelf-edge reefs, and exhibits a corresponding range of roughness values (2.28 ??? D ??? 2.61). ?? 2009 Coastal Education and Research Foundation.

  7. Multi-stage decoding for multi-level block modulation codes

    NASA Technical Reports Server (NTRS)

    Lin, Shu

    1991-01-01

    In this paper, we investigate various types of multi-stage decoding for multi-level block modulation codes, in which the decoding of a component code at each stage can be either soft-decision or hard-decision, maximum likelihood or bounded-distance. Error performance of codes is analyzed for a memoryless additive channel based on various types of multi-stage decoding, and upper bounds on the probability of an incorrect decoding are derived. Based on our study and computation results, we find that, if component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. In particular, we find that the difference in performance between the suboptimum multi-stage soft-decision maximum likelihood decoding of a modulation code and the single-stage optimum decoding of the overall code is very small: only a fraction of dB loss in SNR at the probability of an incorrect decoding for a block of 10(exp -6). Multi-stage decoding of multi-level modulation codes really offers a way to achieve the best of three worlds, bandwidth efficiency, coding gain, and decoding complexity.

  8. An ACOR-Based Multi-Objective WSN Deployment Example for Lunar Surveying.

    PubMed

    López-Matencio, Pablo

    2016-02-06

    Wireless sensor networks (WSNs) can gather in situ real data measurements and work unattended for long periods, even in remote, rough places. A critical aspect of WSN design is node placement, as this determines sensing capacities, network connectivity, network lifetime and, in short, the whole operational capabilities of the WSN. This paper proposes and studies a new node placement algorithm that focus on these aspects. As a motivating example, we consider a network designed to describe the distribution of helium-3 (³He), a potential enabling element for fusion reactors, on the Moon. ³He is abundant on the Moon's surface, and knowledge of its distribution is essential for future harvesting purposes. Previous data are inconclusive, and there is general agreement that on-site measurements, obtained over a long time period, are necessary to better understand the mechanisms involved in the distribution of this element on the Moon. Although a mission of this type is extremely complex, it allows us to illustrate the main challenges involved in a multi-objective WSN placement problem, i.e., selection of optimal observation sites and maximization of the lifetime of the network. To tackle optimization, we use a recent adaptation of the ant colony optimization (ACOR) metaheuristic, extended to continuous domains. Solutions are provided in the form of a Pareto frontier that shows the optimal equilibria. Moreover, we compared our scheme with the four-directional placement (FDP) heuristic, which was outperformed in all cases.

  9. Low-voltage cross-sectional EBIC for characterisation of GaN-based light emitting devices.

    PubMed

    Moldovan, Grigore; Kazemian, Payam; Edwards, Paul R; Ong, Vincent K S; Kurniawan, Oka; Humphreys, Colin J

    2007-01-01

    Electron beam induced current (EBIC) characterisation can provide detailed information on the influence of crystalline defects on the diffusion and recombination of minority carriers in semiconductors. New developments are required for GaN light emitting devices, which need a cross-sectional approach to provide access to their complex multi-layered structures. A sample preparation approach based on low-voltage Ar ion milling is proposed here and shown to produce a flat cross-section with very limited surface recombination, which enables low-voltage high resolution EBIC characterisation. Dark defects are observed in EBIC images and correlation with cathodoluminescence images identify them as threading dislocations. Emphasis is placed on one-dimensional quantification which is used to show that junction delineation with very good spatial resolution can be achieved, revealing significant roughening of this GaN p-n junction. Furthermore, longer minority carrier diffusion lengths along the c-axis are found at dislocation sites, in both p-GaN and the multi-quantum well (MQW) region. This is attributed to gettering of point defects at threading dislocations in p-GaN and higher escape rate from quantum wells at dislocation sites in the MQW region, respectively. These developments show considerable promise for the use of low-voltage cross-sectional EBIC in the characterisation of point and extended defects in GaN-based devices and it is suggested that this technique will be particularly useful for degradation analysis.

  10. A simulation study of scene confusion factors in sensing soil moisture from orbital radar

    NASA Technical Reports Server (NTRS)

    Ulaby, F. T. (Principal Investigator); Dobson, M. C.; Moezzi, S.; Roth, F. T.

    1983-01-01

    Simulated C-band radar imagery for a 124-km by 108-km test site in eastern Kansas is used to classify soil moisture. Simulated radar resolutions are 100 m by 100 m, 1 km by 1km, and 3 km by 3 km. Distributions of actual near-surface soil moisture are established daily for a 23-day accounting period using a water budget model. Within the 23-day period, three orbital radar overpasses are simulated roughly corresponding to generally moist, wet, and dry soil moisture conditions. The radar simulations are performed by a target/sensor interaction model dependent upon a terrain model, land-use classification, and near-surface soil moisture distribution. The accuracy of soil-moisture classification is evaluated for each single-date radar observation and also for multi-date detection of relative soil moisture change. In general, the results for single-date moisture detection show that 70% to 90% of cropland can be correctly classified to within +/- 20% of the true percent of field capacity. For a given radar resolution, the expected classification accuracy is shown to be dependent upon both the general soil moisture condition and also the geographical distribution of land-use and topographic relief. An analysis of cropland, urban, pasture/rangeland, and woodland subregions within the test site indicates that multi-temporal detection of relative soil moisture change is least sensitive to classification error resulting from scene complexity and topographic effects.

  11. Modeling of BN Lifetime Prediction of a System Based on Integrated Multi-Level Information

    PubMed Central

    Wang, Xiaohong; Wang, Lizhi

    2017-01-01

    Predicting system lifetime is important to ensure safe and reliable operation of products, which requires integrated modeling based on multi-level, multi-sensor information. However, lifetime characteristics of equipment in a system are different and failure mechanisms are inter-coupled, which leads to complex logical correlations and the lack of a uniform lifetime measure. Based on a Bayesian network (BN), a lifetime prediction method for systems that combine multi-level sensor information is proposed. The method considers the correlation between accidental failures and degradation failure mechanisms, and achieves system modeling and lifetime prediction under complex logic correlations. This method is applied in the lifetime prediction of a multi-level solar-powered unmanned system, and the predicted results can provide guidance for the improvement of system reliability and for the maintenance and protection of the system. PMID:28926930

  12. Modeling of BN Lifetime Prediction of a System Based on Integrated Multi-Level Information.

    PubMed

    Wang, Jingbin; Wang, Xiaohong; Wang, Lizhi

    2017-09-15

    Predicting system lifetime is important to ensure safe and reliable operation of products, which requires integrated modeling based on multi-level, multi-sensor information. However, lifetime characteristics of equipment in a system are different and failure mechanisms are inter-coupled, which leads to complex logical correlations and the lack of a uniform lifetime measure. Based on a Bayesian network (BN), a lifetime prediction method for systems that combine multi-level sensor information is proposed. The method considers the correlation between accidental failures and degradation failure mechanisms, and achieves system modeling and lifetime prediction under complex logic correlations. This method is applied in the lifetime prediction of a multi-level solar-powered unmanned system, and the predicted results can provide guidance for the improvement of system reliability and for the maintenance and protection of the system.

  13. A second level of the Saint Petersburg skyline

    NASA Astrophysics Data System (ADS)

    Krasnopolsky, Andrey; Bolotin, Sergey

    2018-03-01

    The article considers the history of the residential development in Saint Petersburg and states corresponding landmark dates. In recent years, changes in the altitude range of the residential development are noted, the influence of this factor on the formation of the city's silhouette is assessed. Reasons for such changes are identified. Attractiveness of high-rise residential complexes for living is assessed. Conclusions are made of tendencies in further housing construction development in terms of its altitude range. It is noted that it is possible to locate multi-storied buildings in the periphery of the city, taking into account specific visual characteristics of the construction site and silhouette of erected buildings; as for central districts, strict regulations regarding the altitude range are needed.

  14. In conversation: high school students talk to students about tobacco use and prevention strategies.

    PubMed

    Plano Clark, Vicki L; Miller, Dana L; Creswell, John W; McVea, Kristine; McEntarffer, Rob; Harter, Lynn M; Mickelson, William T

    2002-11-01

    The purpose of this multi-site qualitative study is to explore how adolescents talk about tobacco use. Sixty-six students in four high schools became co-researchers and led focus group interviews with 205 fellow students. From the interviews, the authors develop a story line that reports how adolescents begin smoking, how smoking becomes a pervasive influence, how attitudes form about smoking, what it means to be a smoker, and, ultimately, student suggestions for tobacco use prevention. Embedded within this story line are complex questions and contradictions. We explore whether peers really are influential, if the media is important, whether smoking is a matter of personal choice, if schools actually promote tobacco use, and whether adolescents can quit smoking.

  15. Transcriptional and chromatin regulation during fasting – The genomic era

    PubMed Central

    Goldstein, Ido; Hager, Gordon L.

    2015-01-01

    An elaborate metabolic response to fasting is orchestrated by the liver and is heavily reliant upon transcriptional regulation. In response to hormones (glucagon, glucocorticoids) many transcription factors (TFs) are activated and regulate various genes involved in metabolic pathways aimed at restoring homeostasis: gluconeogenesis, fatty acid oxidation, ketogenesis and amino acid shuttling. We summarize the recent discoveries regarding fasting-related TFs with an emphasis on genome-wide binding patterns. Collectively, the summarized findings reveal a large degree of co-operation between TFs during fasting which occurs at motif-rich DNA sites bound by a combination of TFs. These new findings implicate transcriptional and chromatin regulation as major determinants of the response to fasting and unravels the complex, multi-TF nature of this response. PMID:26520657

  16. 22Lo741: A Nineteenth Century Multipurpose Light Industrial Site in Lowndes County, Mississippi.

    DTIC Science & Technology

    1983-05-01

    R136 554 22L0741: A NINETEENTH CENTURY MULTIPURPOSE LIGHT 1/3 INDUSTRIAL SITE IN LOWND.-(U) MICHIGAN STATE UNIV EAST LANSING ANTHROPOLOGY DIV N J...Tombigbee River Multi- Resource District, Tennessee-Tombigbee Waterway, Alabama and SMssissippi. This relates specifically to the settlement system ...Multi- Resource District and the explanation of their location and individual development. With regard to the economic and distribution systems the

  17. Multi-hazard risk assessment applied to hydraulic fracturing operations

    NASA Astrophysics Data System (ADS)

    Garcia-Aristizabal, Alexander; Gasparini, Paolo; Russo, Raffaella; Capuano, Paolo

    2017-04-01

    Without exception, the exploitation of any energy resource produces impacts and intrinsically bears risks. Therefore, to make sound decisions about future energy resource exploitation, it is important to clearly understand the potential environmental impacts in the full life-cycle of an energy development project, distinguishing between the specific impacts intrinsically related to exploiting a given energy resource and those shared with the exploitation of other energy resources. Technological advances as directional drilling and hydraulic fracturing have led to a rapid expansion of unconventional resources (UR) exploration and exploitation; as a consequence, both public health and environmental concerns have risen. The main objective of a multi-hazard risk assessment applied to the development of UR is to assess the rate (or the likelihood) of occurrence of incidents and the relative potential impacts on surrounding environment, considering different hazards and their interactions. Such analyses have to be performed considering the different stages of development of a project; however, the discussion in this paper is mainly focused on the analysis applied to the hydraulic fracturing stage of a UR development project. The multi-hazard risk assessment applied to the development of UR poses a number of challenges, making of this one a particularly complex problem. First, a number of external hazards might be considered as potential triggering mechanisms. Such hazards can be either of natural origin or anthropogenic events caused by the same industrial activities. Second, failures might propagate through the industrial elements, leading to complex scenarios according to the layout of the industrial site. Third, there is a number of potential risk receptors, ranging from environmental elements (as the air, soil, surface water, or groundwater) to local communities and ecosystems. The multi-hazard risk approach for this problem is set by considering multiple hazards (and their possible interactions) as possible sources of system's perturbation that might drive to the development of an incidental event. Given the complexity of the problem, we adopt a multi-level approach: first, perform a qualitative analysis oriented to the identification of a wide range of possible scenarios; this process is based on a review of potential impacts in different risk receptors reported in literature, which is condensed in a number of causal diagrams created for different stages of a UR development project. Second, the most important scenarios for quantitative multi-hazard risk analyses are selected for further quantification. This selection is based on the identification of major risks, i.e., those related with the occurrence of low probability/high impact extreme events. The general framework for the quantitative multi-hazard risk analysis is represented using a so-called bow-tie structure. It is composed of a fault tree on the left hand side of the graphic plot, identifying the possible events causing the critical (or top) event, and an event tree on the right-hand side showing the possible consequences of the critical event. This work was supported under SHEER: "Shale Gas Exploration and Exploitation Induced Risks" project n.640896, funded from Horizon 2020 - R&I Framework Programme, call H2020-LCE-2014-1

  18. Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy.

    PubMed

    Murthy, Vaibhav; Dacus, Dalton; Gamez, Monica; Hu, Changkun; Wendel, Sebastian O; Snow, Jazmine; Kahn, Andrew; Walterhouse, Stephen H; Wallace, Nicholas A

    2018-06-08

    The repair of double-stranded breaks (DSBs) in DNA is a highly coordinated process, necessitating the formation and resolution of multi-protein repair complexes. This process is regulated by a myriad of proteins that promote the association and disassociation of proteins to these lesions. Thanks in large part to the ability to perform functional screens of a vast library of proteins, there is a greater appreciation of the genes necessary for the double-strand DNA break repair. Often knockout or chemical inhibitor screens identify proteins involved in repair processes by using increased toxicity as a marker for a protein that is required for DSB repair. Although useful for identifying novel cellular proteins involved in maintaining genome fidelity, functional analysis requires the determination of whether the protein of interest promotes localization, formation, or resolution of repair complexes. The accumulation of repair proteins can be readily detected as distinct nuclear foci by immunofluorescence microscopy. Thus, association and disassociation of these proteins at sites of DNA damage can be accessed by observing these nuclear foci at representative intervals after the induction of double-strand DNA breaks. This approach can also identify mis-localized repair factor proteins, if repair defects do not simultaneously occur with incomplete delays in repair. In this scenario, long-lasting double-strand DNA breaks can be engineered by expressing a rare cutting endonuclease (e.g., I-SceI) in cells where the recognition site for the said enzyme has been integrated into the cellular genome. The resulting lesion is particularly hard to resolve as faithful repair will reintroduce the enzyme's recognition site, prompting another round of cleavage. As a result, differences in the kinetics of repair are eliminated. If repair complexes are not formed, localization has been impeded. This protocol describes the methodology necessary to identify changes in repair kinetics as well as repair protein localization.

  19. Complexity of line-seru conversion for different scheduling rules and two improved exact algorithms for the multi-objective optimization.

    PubMed

    Yu, Yang; Wang, Sihan; Tang, Jiafu; Kaku, Ikou; Sun, Wei

    2016-01-01

    Productivity can be greatly improved by converting the traditional assembly line to a seru system, especially in the business environment with short product life cycles, uncertain product types and fluctuating production volumes. Line-seru conversion includes two decision processes, i.e., seru formation and seru load. For simplicity, however, previous studies focus on the seru formation with a given scheduling rule in seru load. We select ten scheduling rules usually used in seru load to investigate the influence of different scheduling rules on the performance of line-seru conversion. Moreover, we clarify the complexities of line-seru conversion for ten different scheduling rules from the theoretical perspective. In addition, multi-objective decisions are often used in line-seru conversion. To obtain Pareto-optimal solutions of multi-objective line-seru conversion, we develop two improved exact algorithms based on reducing time complexity and space complexity respectively. Compared with the enumeration based on non-dominated sorting to solve multi-objective problem, the two improved exact algorithms saves computation time greatly. Several numerical simulation experiments are performed to show the performance improvement brought by the two proposed exact algorithms.

  20. The status of US multi-campus colleges and schools of pharmacy.

    PubMed

    Harrison, Lauren C; Congdon, Heather Brennan; DiPiro, Joseph T

    2010-09-10

    To assess the current status of multi-campus colleges and schools of pharmacy within the United States. Data on multi-campus programs, technology, communication, and opinions regarding benefits and challenges were collected from Web sites, e-mail, and phone interviews from all colleges and schools of pharmacy with students in class on more than 1 campus. Twenty schools and colleges of pharmacy (18 public and 2 private) had multi-campus programs; 16 ran parallel campuses and 4 ran sequential campuses. Most programs used synchronous delivery of classes. The most frequently reported reasons for establishing the multi-campus program were to have access to a hospital and/or medical campus and clinical resources located away from the main campus and to increase class size. Effectiveness of distance education technology was most often sited as a challenge. About 20% of colleges and schools of pharmacy have multi-campus programs most often to facilitate access to clinical resources and to increase class size. These programs expand learning opportunities and face challenges related to technology, resources, and communication.

  1. The Status of US Multi-campus Colleges and Schools of Pharmacy

    PubMed Central

    Harrison, Lauren C.; DiPiro, Joseph T.

    2010-01-01

    Objective To assess the current status of multi-campus colleges and schools of pharmacy within the United States. Methods Data on multi-campus programs, technology, communication, and opinions regarding benefits and challenges were collected from Web sites, e-mail, and phone interviews from all colleges and schools of pharmacy with students in class on more than 1 campus. Results Twenty schools and colleges of pharmacy (18 public and 2 private) had multi-campus programs; 16 ran parallel campuses and 4 ran sequential campuses. Most programs used synchronous delivery of classes. The most frequently reported reasons for establishing the multi-campus program were to have access to a hospital and/or medical campus and clinical resources located away from the main campus and to increase class size. Effectiveness of distance education technology was most often sited as a challenge. Conclusion About 20% of colleges and schools of pharmacy have multi-campus programs most often to facilitate access to clinical resources and to increase class size. These programs expand learning opportunities and face challenges related to technology, resources, and communication. PMID:21088729

  2. A Complex Systems Approach to More Resilient Multi-Layered Security Systems

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

    Brown, Nathanael J. K.; Jones, Katherine A.; Bandlow, Alisa

    In July 2012, protestors cut through security fences and gained access to the Y-12 National Security Complex. This was believed to be a highly reliable, multi-layered security system. This report documents the results of a Laboratory Directed Research and Development (LDRD) project that created a consistent, robust mathematical framework using complex systems analysis algorithms and techniques to better understand the emergent behavior, vulnerabilities and resiliency of multi-layered security systems subject to budget constraints and competing security priorities. Because there are several dimensions to security system performance and a range of attacks that might occur, the framework is multi-objective for amore » performance frontier to be estimated. This research explicitly uses probability of intruder interruption given detection (P I) as the primary resilience metric. We demonstrate the utility of this framework with both notional as well as real-world examples of Physical Protection Systems (PPSs) and validate using a well-established force-on-force simulation tool, Umbra.« less

  3. Resolving dual binding conformations of cellulosome cohesin-dockerin complexes using single-molecule force spectroscopy.

    PubMed

    Jobst, Markus A; Milles, Lukas F; Schoeler, Constantin; Ott, Wolfgang; Fried, Daniel B; Bayer, Edward A; Gaub, Hermann E; Nash, Michael A

    2015-10-31

    Receptor-ligand pairs are ordinarily thought to interact through a lock and key mechanism, where a unique molecular conformation is formed upon binding. Contrary to this paradigm, cellulosomal cohesin-dockerin (Coh-Doc) pairs are believed to interact through redundant dual binding modes consisting of two distinct conformations. Here, we combined site-directed mutagenesis and single-molecule force spectroscopy (SMFS) to study the unbinding of Coh:Doc complexes under force. We designed Doc mutations to knock out each binding mode, and compared their single-molecule unfolding patterns as they were dissociated from Coh using an atomic force microscope (AFM) cantilever. Although average bulk measurements were unable to resolve the differences in Doc binding modes due to the similarity of the interactions, with a single-molecule method we were able to discriminate the two modes based on distinct differences in their mechanical properties. We conclude that under native conditions wild-type Doc from Clostridium thermocellum exocellulase Cel48S populates both binding modes with similar probabilities. Given the vast number of Doc domains with predicted dual binding modes across multiple bacterial species, our approach opens up new possibilities for understanding assembly and catalytic properties of a broad range of multi-enzyme complexes.

  4. NUCLEAR FACTOR Y Transcription Factors Have Both Opposing and Additive Roles in ABA-Mediated Seed Germination

    PubMed Central

    Kumimoto, Roderick W.; Siriwardana, Chamindika L.; Gayler, Krystal K.; Risinger, Jan R.; Siefers, Nicholas; Holt, Ben F.

    2013-01-01

    In the model organism Arabidopsis thaliana the heterotrimeric transcription factor NUCLEAR FACTOR Y (NF-Y) has been shown to play multiple roles in facilitating plant growth and development. Although NF-Y itself represents a multi-protein transcriptional complex, recent studies have shown important interactions with other transcription factors, especially those in the bZIP family. Here we add to the growing evidence that NF-Y and bZIP form common complexes to affect many processes. We carried out transcriptional profiling on nf-yc mutants and through subsequent analyses found an enrichment of bZIP binding sites in the promoter elements of misregulated genes. Using NF-Y as bait, yeast two hybrid assays yielded interactions with bZIP proteins that are known to control ABA signaling. Accordingly, we find that plants mutant for several NF-Y subunits show characteristic phenotypes associated with the disruption of ABA signaling. While previous reports have shown additive roles for NF-YC family members in photoperiodic flowering, we found that they can have opposing roles in ABA signaling. Collectively, these results demonstrated the importance and complexity of NF-Y in the integration of environmental and hormone signals. PMID:23527203

  5. Facebook Advertising Across an Engagement Spectrum: A Case Example for Public Health Communication.

    PubMed

    Platt, Tevah; Platt, Jodyn; Thiel, Daniel B; Kardia, Sharon L R

    2016-05-30

    The interpersonal, dialogic features of social networking sites have untapped potential for public health communication. We ran a Facebook advertising campaign to raise statewide awareness of Michigan's newborn screening and biobanking programs. We ran a Facebook advertising campaign to stimulate public engagement on the complex and sensitive issue of Michigan's newborn screening and biobank programs. We ran an 11-week, US $15,000 Facebook advertising campaign engaging Michigan Facebook users aged 18-64 years about the state's newborn screening and population biobank programs, and we used a novel "engagement spectrum" framework to contextualize and evaluate engagement outcomes ranging from observation to multi-way conversation. The campaign reached 1.88 million Facebook users, yielding a range of engagement outcomes across ad sets that varied by objective, content, budget, duration, and bid type. Ad sets yielded 9009 page likes (US $4125), 15,958 website clicks (US $5578), and 12,909 complete video views to 100% (US $3750). "Boosted posts" yielded 528 comments and 35,966 page post engagements (US $1500). Overall, the campaign led to 452 shares and 642 comments, including 176 discussing newborn screening and biobanking. Facebook advertising campaigns can efficiently reach large populations and achieve a range of engagement outcomes by diversifying ad types, bid types, and content. This campaign provided a population-based approach to communication that also increased transparency on a sensitive and complex topic by creating a forum for multi-way interaction.

  6. Inside the "African cattle complex": animal burials in the holocene central Sahara.

    PubMed

    di Lernia, Savino; Tafuri, Mary Anne; Gallinaro, Marina; Alhaique, Francesca; Balasse, Marie; Cavorsi, Lucia; Fullagar, Paul D; Mercuri, Anna Maria; Monaco, Andrea; Perego, Alessandro; Zerboni, Andrea

    2013-01-01

    Cattle pastoralism is an important trait of African cultures. Ethnographic studies describe the central role played by domestic cattle within many societies, highlighting its social and ideological value well beyond its mere function as 'walking larder'. Historical depth of this African legacy has been repeatedly assessed in an archaeological perspective, mostly emphasizing a continental vision. Nevertheless, in-depth site-specific studies, with a few exceptions, are lacking. Despite the long tradition of a multi-disciplinary approach to the analysis of pastoral systems in Africa, rarely do early and middle Holocene archaeological contexts feature in the same area the combination of settlement, ceremonial and rock art features so as to be multi-dimensionally explored: the Messak plateau in the Libyan central Sahara represents an outstanding exception. Known for its rich Pleistocene occupation and abundant Holocene rock art, the region, through our research, has also shown to preserve the material evidence of a complex ritual dated to the Middle Pastoral (6080-5120 BP or 5200-3800 BC). This was centred on the frequent deposition in stone monuments of disarticulated animal remains, mostly cattle. Animal burials are known also from other African contexts, but regional extent of the phenomenon, state of preservation of monuments, and associated rock art make the Messak case unique. GIS analysis, excavation data, radiocarbon dating, zooarchaeological and isotopic (Sr, C, O) analyses of animal remains, and botanical information are used to explore this highly formalized ritual and the lifeways of a pastoral community in the Holocene Sahara.

  7. Facebook Advertising Across an Engagement Spectrum: A Case Example for Public Health Communication

    PubMed Central

    Platt, Jodyn; Thiel, Daniel B; Kardia, Sharon L. R

    2016-01-01

    Background The interpersonal, dialogic features of social networking sites have untapped potential for public health communication. We ran a Facebook advertising campaign to raise statewide awareness of Michigan’s newborn screening and biobanking programs. Objective We ran a Facebook advertising campaign to stimulate public engagement on the complex and sensitive issue of Michigan’s newborn screening and biobank programs. Methods We ran an 11-week, US $15,000 Facebook advertising campaign engaging Michigan Facebook users aged 18-64 years about the state’s newborn screening and population biobank programs, and we used a novel “engagement spectrum” framework to contextualize and evaluate engagement outcomes ranging from observation to multi-way conversation. Results The campaign reached 1.88 million Facebook users, yielding a range of engagement outcomes across ad sets that varied by objective, content, budget, duration, and bid type. Ad sets yielded 9009 page likes (US $4125), 15,958 website clicks (US $5578), and 12,909 complete video views to 100% (US $3750). “Boosted posts” yielded 528 comments and 35,966 page post engagements (US $1500). Overall, the campaign led to 452 shares and 642 comments, including 176 discussing newborn screening and biobanking. Conclusions Facebook advertising campaigns can efficiently reach large populations and achieve a range of engagement outcomes by diversifying ad types, bid types, and content. This campaign provided a population-based approach to communication that also increased transparency on a sensitive and complex topic by creating a forum for multi-way interaction. PMID:27244774

  8. Analysis of Multi-Criteria Evaluation Method of Landfill Site Selection for Municipal Solid Waste Management

    NASA Astrophysics Data System (ADS)

    Mohammed, Habiba Ibrahim; Majid, Zulkepli; Yusof, Norhakim Bin; Bello Yamusa, Yamusa

    2018-03-01

    Landfilling remains the most common systematic technique of solid waste disposal in most of the developed and developing countries. Finding a suitable site for landfill is a very challenging task. Landfill site selection process aims to provide suitable areas that will protect the environment and public health from pollution and hazards. Therefore, various factors such as environmental, physical, socio-economic, and geological criteria must be considered before siting any landfill. This makes the site selection process vigorous and tedious because it involves the processing of large amount of spatial data, rules and regulations from different agencies and also policy from decision makers. This allows the incorporation of conflicting objectives and decision maker preferences into spatial decision models. This paper particularly analyzes the multi-criteria evaluation (MCE) method of landfill site selection for solid waste management by means of literature reviews and surveys. The study will help the decision makers and waste management authorities to choose the most effective method when considering landfill site selection.

  9. Multi-stage decoding for multi-level block modulation codes

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Kasami, Tadao

    1991-01-01

    Various types of multistage decoding for multilevel block modulation codes, in which the decoding of a component code at each stage can be either soft decision or hard decision, maximum likelihood or bounded distance are discussed. Error performance for codes is analyzed for a memoryless additive channel based on various types of multi-stage decoding, and upper bounds on the probability of an incorrect decoding are derived. It was found that, if component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. It was found that the difference in performance between the suboptimum multi-stage soft decision maximum likelihood decoding of a modulation code and the single stage optimum decoding of the overall code is very small, only a fraction of dB loss in SNR at the probability of an incorrect decoding for a block of 10(exp -6). Multi-stage decoding of multi-level modulation codes really offers a way to achieve the best of three worlds, bandwidth efficiency, coding gain, and decoding complexity.

  10. Astronomy Village Reaches for New Heights

    NASA Astrophysics Data System (ADS)

    Croft, S. K.; Pompea, S. M.

    2007-12-01

    We are developing a set of complex, multimedia-based instructional modules emphasizing technical and scientific issues related to Giant Segmented Mirror Telescope project. The modules" pedagogy will be open-ended and problem-based to promote development of problem-solving skills. Problem- based-learning modules that emphasize work on open-ended complex real world problems are particularly valuable in illustrating and promoting a perspective on the process of science and engineering. Research in this area shows that these kinds of learning experiences are superior to more conventional student training in terms of gains in student learning. The format for the modules will be based on the award-winning multi-media educational Astronomy Village products that present students with a simulated environment: a mountaintop community surrounded by a cluster of telescopes, satellite receivers, and telecommunication towers. A number of "buildings" are found in the Village, such as a library, a laboratory, and an auditorium. Each building contains an array of information sources and computer simulations. Students navigate through their research with a mentor via imbedded video. The first module will be "Observatory Site Selection." Students will use astronomical data, basic weather information, and sky brightness data to select the best site for an observatory. Students will investigate the six GSMT sites considered by the professional site selection teams. Students will explore weather and basic site issues (e.g., roads and topography) using remote sensing images, computational fluid dynamics results, turbulence profiles, and scintillation of the different sites. Comparison of student problem solving with expert problem solving will also be done as part of the module. As part of a site selection team they will have to construct a case and present it on why they chose a particular site. The second module will address aspects of system engineering and optimization for a GSMT-like telescope. Basic system issues will be addressed and studied. These might include various controls issues and optimization issues such as mirror figure, mirror support stability, and wind loading trade-offs. Using system modeling and system optimization results from existing and early GSMT trade studies, we will create a simulation where students are part of an engineering design and optimization team. They will explore the cost/performance/schedule issues associate with the GSMT design.

  11. Mass spectrometric measurements of the isotopic anatomies of molecules (Invited)

    NASA Astrophysics Data System (ADS)

    Eiler, J. M.; Krumwiede, D.; Schlueter, H.

    2013-12-01

    Site-specific and multiple isotopic substitutions in molecular structures potentially provide an extraordinarily rich set of constraints on their sources, conditions of formation, reaction and transport histories, and perhaps other issues. Examples include carbonate ';clumped isotope' thermometry, clumped isotope measurements of CO2, O2, and, recently, methane, ethane and N2O; site-specific 15N measurements in N2O and 13C and D analyses of fatty acids, sugars, cellulose, food products, and, recently, n-alkanes. Extension of the principles behind these tools to the very large number of isotopologues of complex molecules could potentially lead to new uses of isotope chemistry, similar to proteomics, metabolomics and genomics in their complexity and depth of detail (';isotomics'?). Several technologies are potentially useful for this field, including ';SNIF-NMR', gas source mass spectrometry and IR absorption spectroscopy. However, all well established methods have restrictive limits in the sizes of samples, types of analyzes, and the sorts of isotopologues that can be measured with useful precision. We will present an overview of several emerging instruments and techniques of high-resolution gas source mass spectrometry that may enable study of a large proportion of the isotopologues of a wide range of volatile and semi-volatile compounds, including many organics, with precisions and sample sizes suitable for a range of applications. A variety of isotopologues can be measured by combining information from the Thermo 253 Ultra (a new high resolution, multi-collector gas source mass spectrometer) and the Thermo DFS (a very high resolution single collector, but used here on a novel mode to achieve ~per mil precision ratio measurements), sometimes supplemented by conventional bulk isotopic measurements. It is possible to design methods in which no one of these sources of data meaningfully constrain abundances of specific isotopologues, but their combination fully and precisely constrains a large number. We have assembled a suite of instruments (including the prototype of the Ultra, and a modified version of the DFS that is capable of dual inlet analyses) that make it logistically straightforward to perform such multi-instrument analyses. Examples will be presented documenting the accuracy of these techniques for systems that are independently well known (e.g., isotopologues of methane), and the precision and internal consistency of results for larger, more complex molecules (e.g., a suite of singly and doubly substituted isotopologues of hexane and other moderate-molecular-weight organics).

  12. Multi-Phase Extraction: State-of-the-Practice

    EPA Pesticide Factsheets

    This report describes the state-of-the-practice for multi-phase extraction (MPE) of contaminated soil and groundwater, focusing primarily on the application and use of MPE at sites with halogenated volatile organic compounds (VOCs).

  13. STATIC AND KINETIC SITE-SPECIFIC PROTEIN-DNA PHOTOCROSSLINKING: ANALYSIS OF BACTERIAL TRANSCRIPTION INITIATION COMPLEXES

    PubMed Central

    Naryshkin, Nikolai; Druzhinin, Sergei; Revyakin, Andrei; Kim, Younggyu; Mekler, Vladimir; Ebright, Richard H.

    2009-01-01

    Static site-specific protein-DNA photocrosslinking permits identification of protein-DNA interactions within multiprotein-DNA complexes. Kinetic site-specific protein-DNA photocrosslinking--involving rapid-quench-flow mixing and pulsed-laser irradiation--permits elucidation of pathways and kinetics of formation of protein-DNA interactions within multiprotein-DNA complexes. We present detailed protocols for application of static and kinetic site-specific protein-DNA photocrosslinking to bacterial transcription initiation complexes. PMID:19378179

  14. Design of convolutional tornado code

    NASA Astrophysics Data System (ADS)

    Zhou, Hui; Yang, Yao; Gao, Hongmin; Tan, Lu

    2017-09-01

    As a linear block code, the traditional tornado (tTN) code is inefficient in burst-erasure environment and its multi-level structure may lead to high encoding/decoding complexity. This paper presents a convolutional tornado (cTN) code which is able to improve the burst-erasure protection capability by applying the convolution property to the tTN code, and reduce computational complexity by abrogating the multi-level structure. The simulation results show that cTN code can provide a better packet loss protection performance with lower computation complexity than tTN code.

  15. Defocusing complex short-pulse equation and its multi-dark-soliton solution.

    PubMed

    Feng, Bao-Feng; Ling, Liming; Zhu, Zuonong

    2016-05-01

    In this paper, we propose a complex short-pulse equation of both focusing and defocusing types, which governs the propagation of ultrashort pulses in nonlinear optical fibers. It can be viewed as an analog of the nonlinear Schrödinger (NLS) equation in the ultrashort-pulse regime. Furthermore, we construct the multi-dark-soliton solution for the defocusing complex short-pulse equation through the Darboux transformation and reciprocal (hodograph) transformation. One- and two-dark-soliton solutions are given explicitly, whose properties and dynamics are analyzed and illustrated.

  16. On the use of multi-agent systems for the monitoring of industrial systems

    NASA Astrophysics Data System (ADS)

    Rezki, Nafissa; Kazar, Okba; Mouss, Leila Hayet; Kahloul, Laid; Rezki, Djamil

    2016-03-01

    The objective of the current paper is to present an intelligent system for complex process monitoring, based on artificial intelligence technologies. This system aims to realize with success all the complex process monitoring tasks that are: detection, diagnosis, identification and reconfiguration. For this purpose, the development of a multi-agent system that combines multiple intelligences such as: multivariate control charts, neural networks, Bayesian networks and expert systems has became a necessity. The proposed system is evaluated in the monitoring of the complex process Tennessee Eastman process.

  17. Evaluating Multi-Input/Multi-Output Digital Control Systems

    NASA Technical Reports Server (NTRS)

    Pototzky, Anthony S.; Wieseman, Carol D.; Hoadley, Sherwood T.; Mukhopadhyay, Vivek

    1994-01-01

    Controller-performance-evaluation (CPE) methodology for multi-input/multi-output (MIMO) digital control systems developed. Procedures identify potentially destabilizing controllers and confirm satisfactory performance of stabilizing ones. Methodology generic and used in many types of multi-loop digital-controller applications, including digital flight-control systems, digitally controlled spacecraft structures, and actively controlled wind-tunnel models. Also applicable to other complex, highly dynamic digital controllers, such as those in high-performance robot systems.

  18. Integrating multi-criteria decision analysis for a GIS-based hazardous waste landfill sitting in Kurdistan Province, western Iran

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

    Sharifi, Mozafar; Hadidi, Mosslem; Vessali, Elahe

    2009-10-15

    The evaluation of a hazardous waste disposal site is a complicated process because it requires data from diverse social and environmental fields. These data often involve processing of a significant amount of spatial information which can be used by GIS as an important tool for land use suitability analysis. This paper presents a multi-criteria decision analysis alongside with a geospatial analysis for the selection of hazardous waste landfill sites in Kurdistan Province, western Iran. The study employs a two-stage analysis to provide a spatial decision support system for hazardous waste management in a typically under developed region. The purpose ofmore » GIS was to perform an initial screening process to eliminate unsuitable land followed by utilization of a multi-criteria decision analysis (MCDA) to identify the most suitable sites using the information provided by the regional experts with reference to new chosen criteria. Using 21 exclusionary criteria, as input layers, masked maps were prepared. Creating various intermediate or analysis map layers a final overlay map was obtained representing areas for hazardous waste landfill sites. In order to evaluate different landfill sites produced by the overlaying a landfill suitability index system was developed representing cumulative effects of relative importance (weights) and suitability values of 14 non-exclusionary criteria including several criteria resulting from field observation. Using this suitability index 15 different sites were visited and based on the numerical evaluation provided by MCDA most suitable sites were determined.« less

  19. Integrating multi-criteria decision analysis for a GIS-based hazardous waste landfill sitting in Kurdistan Province, western Iran.

    PubMed

    Sharifi, Mozafar; Hadidi, Mosslem; Vessali, Elahe; Mosstafakhani, Parasto; Taheri, Kamal; Shahoie, Saber; Khodamoradpour, Mehran

    2009-10-01

    The evaluation of a hazardous waste disposal site is a complicated process because it requires data from diverse social and environmental fields. These data often involve processing of a significant amount of spatial information which can be used by GIS as an important tool for land use suitability analysis. This paper presents a multi-criteria decision analysis alongside with a geospatial analysis for the selection of hazardous waste landfill sites in Kurdistan Province, western Iran. The study employs a two-stage analysis to provide a spatial decision support system for hazardous waste management in a typically under developed region. The purpose of GIS was to perform an initial screening process to eliminate unsuitable land followed by utilization of a multi-criteria decision analysis (MCDA) to identify the most suitable sites using the information provided by the regional experts with reference to new chosen criteria. Using 21 exclusionary criteria, as input layers, masked maps were prepared. Creating various intermediate or analysis map layers a final overlay map was obtained representing areas for hazardous waste landfill sites. In order to evaluate different landfill sites produced by the overlaying a landfill suitability index system was developed representing cumulative effects of relative importance (weights) and suitability values of 14 non-exclusionary criteria including several criteria resulting from field observation. Using this suitability index 15 different sites were visited and based on the numerical evaluation provided by MCDA most suitable sites were determined.

  20. Multi-Mode Binding of Cellobiohydrolase Cel7A from Trichoderma reesei to Cellulose

    PubMed Central

    Jalak, Jürgen; Väljamäe, Priit

    2014-01-01

    Enzymatic hydrolysis of recalcitrant polysaccharides like cellulose takes place on the solid-liquid interface. Therefore the adsorption of enzymes to the solid surface is a pre-requisite for catalysis. Here we used enzymatic activity measurements with fluorescent model-substrate 4-methyl-umbelliferyl-β-D-lactoside for sensitive monitoring of the binding of cellobiohydrolase TrCel7A from Trichoderma reesei to bacterial cellulose (BC). The binding at low nanomolar free TrCel7A concentrations was exclusively active site mediated and was consistent with Langmuir's one binding site model with K d and A max values of 2.9 nM and 126 nmol/g BC, respectively. This is the strongest binding observed with non-complexed cellulases and apparently represents the productive binding of TrCel7A to cellulose chain ends on the hydrophobic face of BC microfibril. With increasing free TrCel7A concentrations the isotherm gradually deviated from the Langmuir's one binding site model. This was caused by the increasing contribution of lower affinity binding modes that included both active site mediated binding and non-productive binding with active site free from cellulose chain. The binding of TrCel7A to BC was found to be only partially reversible. Furthermore, the isotherm was dependent on the concentration of BC with more efficient binding observed at lower BC concentrations. The phenomenon can be ascribed to the BC concentration dependent aggregation of BC microfibrils with concomitant reduction of specific surface area. PMID:25265511

  1. Progress on New Hepatitis C Virus Targets: NS2 and NS5A

    NASA Astrophysics Data System (ADS)

    Marcotrigiano, Joseph

    Hepatitis C virus (HCV) is a major global health problem, affecting about 170 million people worldwide. Chronic infection can lead to cirrhosis and liver cancer. The replication machine of HCV is a multi-subunit membrane associated complex, consisting of nonstructural proteins (NS2-5B), which replicate the viral RNA genome. The structures of NS5A and NS2 were recently determined. NS5A is an essential replicase component that also modulates numerous cellular processes ranging from innate immunity to cell growth and survival. The structure reveals a novel protein fold, a new zinc coordination motif, a disulfide bond and a dimer interface. Analysis of molecular surfaces suggests the location of the membrane interaction surface of NS5A, as well as hypothetical protein and RNA binding sites. NS2 is one of two virally encoded proteases that are required for processing the viral polyprotein into the mature nonstructural proteins. NS2 is a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer and the nucleophilic cysteine by the other. The C-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. The structure also reveals possible sites of membrane interaction, a rare cis-proline residue, and highly conserved dimer contacts. The novel features of both structures have changed the current view of HCV polyprotein replication and present new opportunities for antiviral drug design.

  2. Flexible Stoichiometry and Asymmetry of the PIDDosome Core Complex by Heteronuclear NMR Spectroscopy and Mass Spectrometry

    PubMed Central

    Nematollahi, Lily A.; Garza-Garcia, Acely; Bechara, Chérine; Esposito, Diego; Morgner, Nina; Robinson, Carol V.; Driscoll, Paul C.

    2015-01-01

    Homotypic death domain (DD)–DD interactions are important in the assembly of oligomeric signaling complexes such as the PIDDosome that acts as a platform for activation of caspase-2-dependent apoptotic signaling. The structure of the PIDDosome core complex exhibits an asymmetric three-layered arrangement containing five PIDD-DDs in one layer, five RAIDD-DDs in a second layer and an additional two RAIDD-DDs. We addressed complex formation between PIDD-DD and RAIDD-DD in solution using heteronuclear nuclear magnetic resonance (NMR) spectroscopy, nanoflow electrospray ionization mass spectrometry and size-exclusion chromatography with multi-angle light scattering. The DDs assemble into complexes displaying molecular masses in the range 130–158 kDa and RAIDD-DD:PIDD-DD stoichiometries of 5:5, 6:5 and 7:5. These data suggest that the crystal structure is representative of only the heaviest species in solution and that two RAIDD-DDs are loosely attached to the 5:5 core. Two-dimensional 1H,15N-NMR experiments exhibited signal loss upon complexation consistent with the formation of high-molecular-weight species. 13C-Methyl-transverse relaxation optimized spectroscopy measurements of the PIDDosome core exhibit signs of differential line broadening, cross-peak splitting and chemical shift heterogeneity that reflect the presence of non-equivalent sites at interfaces within an asymmetric complex. Experiments using a mutant RAIDD-DD that forms a monodisperse 5:5 complex with PIDD-DD show that the spectroscopic signature derives from the quasi- but non-exact equivalent environments of each DD. Since this characteristic was previously demonstrated for the complex between the DDs of CD95 and FADD, the NMR data for this system are consistent with the formation of a structure homologous to the PIDDosome core. PMID:25528640

  3. Single-site neural tube closure in human embryos revisited.

    PubMed

    de Bakker, Bernadette S; Driessen, Stan; Boukens, Bastiaan J D; van den Hoff, Maurice J B; Oostra, Roelof-Jan

    2017-10-01

    Since the multi-site closure theory was first proposed in 1991 as explanation for the preferential localizations of neural tube defects, the closure of the neural tube has been debated. Although the multi-site closure theory is much cited in clinical literature, single-site closure is most apparent in literature concerning embryology. Inspired by Victor Hamburgers (1900-2001) statement that "our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right", we decided to critically review both theories of neural tube closure. To verify the theories of closure, we studied serial histological sections of 10 mouse embryos between 8.5 and 9.5 days of gestation and 18 human embryos of the Carnegie collection between Carnegie stage 9 (19-21 days) and 13 (28-32 days). Neural tube closure was histologically defined by the neuroepithelial remodeling of the two adjoining neural fold tips in the midline. We did not observe multiple fusion sites in neither mouse nor human embryos. A meta-analysis of case reports on neural tube defects showed that defects can occur at any level of the neural axis. Our data indicate that the human neural tube fuses at a single site and, therefore, we propose to reinstate the single-site closure theory for neural tube closure. We showed that neural tube defects are not restricted to a specific location, thereby refuting the reasoning underlying the multi-site closure theory. Clin. Anat. 30:988-999, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Synthesis and characterization of new unsymmetrical Schiff base Zn (II) and Co (II) complexes and study of their interactions with bovin serum albumin and DNA by spectroscopic techniques.

    PubMed

    Sedighipoor, Maryam; Kianfar, Ali Hossein; Sabzalian, Mohammad R; Abyar, Fatemeh

    2018-06-05

    Two novel tetra-coordinated Cobalt(II) and Zinc (II) chelate series with the general formula of [Co (L)·2H 2 O] (1) and [Zn (L)] (2) [L=N-2-hydroxyacetophenon-N'-2-hydroxynaphthaldehyde-1,2 phenylenediimine)] with biologically active Schiff base ligands were synthesized and recognized by elemental analysis and multi-nuclear spectroscopy (IR and 1 H and 13 C NMR); then, their biological activities including DNA and protein interactions were studied. The interaction of the synthesized compounds with bovine serum albumin (BSA) was investigated via fluorescence spectroscopy, showing the affinity of the complexes for these proteins with relatively high binding constant values and the changed secondary BSA structure in the presence of the complexes. The interaction of these compounds with CT-DNA was considered by UV-Vis technique, emission titration, viscosity measurements, helix melting methods, and circular dichroism (CD) spectroscopy, confirming that the complexes were bound to CT-DNA by the intercalation binding mode. Furthermore, the complexes had the capability to displace the DNA-bound MB, as shown by the competitive studies of these complexes with methylene blue (MB), thereby suggesting the intercalation mode for the competition. Finally, the theoretical studies carried out by the docking method were performed to calculate the binding constants and recognize the binding site of the BSA and DNA by the complexes. In addition, in vitro and in silico studies showed that the compounds were degradable by bacterial and fungal biodegradation activities. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Synthesis and characterization of new unsymmetrical Schiff base Zn (II) and Co (II) complexes and study of their interactions with bovin serum albumin and DNA by spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Sedighipoor, Maryam; Kianfar, Ali Hossein; Sabzalian, Mohammad R.; Abyar, Fatemeh

    2018-06-01

    Two novel tetra-coordinated Cobalt(II) and Zinc (II) chelate series with the general formula of [Co (L)·2H2O] (1) and [Zn (L)] (2) [L = N-2-hydroxyacetophenon-N‧-2-hydroxynaphthaldehyde-1,2 phenylenediimine)] with biologically active Schiff base ligands were synthesized and recognized by elemental analysis and multi-nuclear spectroscopy (IR and 1H and 13C NMR); then, their biological activities including DNA and protein interactions were studied. The interaction of the synthesized compounds with bovine serum albumin (BSA) was investigated via fluorescence spectroscopy, showing the affinity of the complexes for these proteins with relatively high binding constant values and the changed secondary BSA structure in the presence of the complexes. The interaction of these compounds with CT-DNA was considered by UV-Vis technique, emission titration, viscosity measurements, helix melting methods, and circular dichroism (CD) spectroscopy, confirming that the complexes were bound to CT-DNA by the intercalation binding mode. Furthermore, the complexes had the capability to displace the DNA-bound MB, as shown by the competitive studies of these complexes with methylene blue (MB), thereby suggesting the intercalation mode for the competition. Finally, the theoretical studies carried out by the docking method were performed to calculate the binding constants and recognize the binding site of the BSA and DNA by the complexes. In addition, in vitro and in silico studies showed that the compounds were degradable by bacterial and fungal biodegradation activities.

  6. Conserving and Enhancing the Natural Environment: A Guide for Planning, Design, Construction, and Maintenance on New & Existing School Sites.

    ERIC Educational Resources Information Center

    Maryland State Dept. of Education, Baltimore. School Facilities Branch.

    Natural environments on school sites provide considerable multi-disciplinary educational opportunities, many of which are "hands-on" experiences that stimulate learning. This document presents guidelines on conserving and enhancing the natural environment on school sites. It provides guidance for developing the site requirements in…

  7. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Sustainable principles for siting, design and construction... FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable principles for siting, design and construction. [Reserved] ...

  8. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Sustainable principles for siting, design and construction... FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable principles for siting, design and construction. [Reserved] ...

  9. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Sustainable principles for siting, design and construction... FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable principles for siting, design and construction. [Reserved] ...

  10. HPV Vaccine Effective at Multiple Anatomic Sites

    Cancer.gov

    A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l

  11. Spread of plague among black-tailed prairie dogs is associated with colony spatial characteristics

    USGS Publications Warehouse

    Johnson, T.L.; Cully, J.F.; Collinge, S.K.; Ray, C.; Frey, C.M.; Sandercock, B.K.

    2011-01-01

    Sylvatic plague (Yersinia pestis) is an exotic pathogen that is highly virulent in black-tailed prairie dogs (Cynomys ludovicianus) and causes widespread colony losses and individual mortality rates >95%. We investigated colony spatial characteristics that may influence inter-colony transmission of plague at 3 prairie dog colony complexes in the Great Plains. The 4 spatial characteristics we considered include: colony size, Euclidean distance to nearest neighboring colony, colony proximity index, and distance to nearest drainage (dispersal) corridor. We used multi-state mark-recapture models to determine the relationship between these colony characteristics and probability of plague transmission among prairie dog colonies. Annual mapping of colonies and mark-recapture analyses of disease dynamics in natural colonies led to 4 main results: 1) plague outbreaks exhibited high spatial and temporal variation, 2) the site of initiation of epizootic plague may have substantially influenced the subsequent inter-colony spread of plague, 3) the long-term effect of plague on individual colonies differed among sites because of how individuals and colonies were distributed, and 4) colony spatial characteristics were related to the probability of infection at all sites although the relative importance and direction of relationships varied among sites. Our findings suggest that conventional prairie dog conservation management strategies, including promoting large, highly connected colonies, may need to be altered in the presence of plague. ?? 2011 The Wildlife Society.

  12. Stereodivergent synthesis with a programmable molecular machine

    NASA Astrophysics Data System (ADS)

    Kassem, Salma; Lee, Alan T. L.; Leigh, David A.; Marcos, Vanesa; Palmer, Leoni I.; Pisano, Simone

    2017-09-01

    It has been convincingly argued that molecular machines that manipulate individual atoms, or highly reactive clusters of atoms, with Ångström precision are unlikely to be realized. However, biological molecular machines routinely position rather less reactive substrates in order to direct chemical reaction sequences, from sequence-specific synthesis by the ribosome to polyketide synthases, where tethered molecules are passed from active site to active site in multi-enzyme complexes. Artificial molecular machines have been developed for tasks that include sequence-specific oligomer synthesis and the switching of product chirality, a photo-responsive host molecule has been described that is able to mechanically twist a bound molecular guest, and molecular fragments have been selectively transported in either direction between sites on a molecular platform through a ratchet mechanism. Here we detail an artificial molecular machine that moves a substrate between different activating sites to achieve different product outcomes from chemical synthesis. This molecular robot can be programmed to stereoselectively produce, in a sequential one-pot operation, an excess of any one of four possible diastereoisomers from the addition of a thiol and an alkene to an α,β-unsaturated aldehyde in a tandem reaction process. The stereodivergent synthesis includes diastereoisomers that cannot be selectively synthesized through conventional iminium-enamine organocatalysis. We anticipate that future generations of programmable molecular machines may have significant roles in chemical synthesis and molecular manufacturing.

  13. Natal and breeding philopatry of female Steller sea lions in southeastern Alaska.

    PubMed

    Hastings, Kelly K; Jemison, Lauri A; Pendleton, Grey W; Raum-Suryan, Kimberly L; Pitcher, Kenneth W

    2017-01-01

    Information on drivers of dispersal is critical for wildlife conservation but is rare for long-lived marine mammal species with large geographic ranges. We fit multi-state mark-recapture models to resighting data of 369 known-aged Steller sea lion (Eumetopias jubatus) females marked as pups on their natal rookeries in southeastern Alaska from 1994-2005 and monitored from 2001-15. We estimated probabilities of females being first observed parous at their natal site (natal philopatry), and of not moving breeding sites among years (breeding philopatry) at large (> 400 km, all five rookeries in southeastern Alaska) and small (< 4 km, all islands within the largest rookery, Forrester Island Complex, F) spatial scales. At the rookery scale, natal philopatry was moderately high (0.776-0.859) for most rookeries and breeding philopatry was nearly 1, with < 3% of females switching breeding rookeries between years. At more populous islands at F, natal philopatry was 0.500-0.684 versus 0.295-0.437 at less populous islands, and breeding philopatry was 0.919-0.926 versus 0.604-0.858. At both spatial scales, the probability of pupping at a non-natal site increased with population size of, and declined with distance from, the destination site. Natal philopatry of < 1 would increase gene flow, improve population resilience, and promote population recovery after decline in a heterogeneous environment. Very high breeding philopatry suggests that familiarity with neighboring females and knowledge of the breeding site (the topography of pupping sites and nearby foraging locations) may be a critical component to reproductive strategies of sea lions.

  14. Multi-scale approach to the environmental factors effects on spatio-temporal variability of Chironomus salinarius (Diptera: Chironomidae) in a French coastal lagoon

    NASA Astrophysics Data System (ADS)

    Cartier, V.; Claret, C.; Garnier, R.; Fayolle, S.; Franquet, E.

    2010-03-01

    The complexity of the relationships between environmental factors and organisms can be revealed by sampling designs which consider the contribution to variability of different temporal and spatial scales, compared to total variability. From a management perspective, a multi-scale approach can lead to time-saving. Identifying environmental patterns that help maintain patchy distribution is fundamental in studying coastal lagoons, transition zones between continental and marine waters characterised by great environmental variability on spatial and temporal scales. They often present organic enrichment inducing decreased species richness and increased densities of opportunist species like C hironomus salinarius, a common species that tends to swarm and thus constitutes a nuisance for human populations. This species is dominant in the Bolmon lagoon, a French Mediterranean coastal lagoon under eutrophication. Our objective was to quantify variability due to both spatial and temporal scales and identify the contribution of different environmental factors to this variability. The population of C. salinarius was sampled from June 2007 to June 2008 every two months at 12 sites located in two areas of the Bolmon lagoon, at two different depths, with three sites per area-depth combination. Environmental factors (temperature, dissolved oxygen both in sediment and under water surface, sediment organic matter content and grain size) and microbial activities (i.e. hydrolase activities) were also considered as explanatory factors of chironomid densities and distribution. ANOVA analysis reveals significant spatial differences regarding the distribution of chironomid larvae for the area and the depth scales and their interaction. The spatial effect is also revealed for dissolved oxygen (water), salinity and fine particles (area scale), and for water column depth. All factors but water column depth show a temporal effect. Spearman's correlations highlight the seasonal effect (temperature, dissolved oxygen in sediment and water) as well as the effect of microbial activities on chironomid larvae. Our results show that a multi-scale approach identifies patchy distribution, even when there is relative environmental homogeneity.

  15. How can healthcare organizations implement patient-centered care? Examining a large-scale cultural transformation.

    PubMed

    Bokhour, Barbara G; Fix, Gemmae M; Mueller, Nora M; Barker, Anna M; Lavela, Sherri L; Hill, Jennifer N; Solomon, Jeffrey L; Lukas, Carol VanDeusen

    2018-03-07

    Healthcare organizations increasingly are focused on providing care which is patient-centered rather than disease-focused. Yet little is known about how best to transform the culture of care in these organizations. We sought to understand key organizational factors for implementing patient-centered care cultural transformation through an examination of efforts in the US Department of Veterans Affairs. We conducted multi-day site visits at four US Department of Veterans Affairs medical centers designated as leaders in providing patient-centered care. We conducted qualitative semi-structured interviews with 108 employees (22 senior leaders, 42 middle managers, 37 front-line providers and 7 staff). Transcripts of audio recordings were analyzed using a priori codes based on the Consolidated Framework for Implementation Research. We used constant comparison analysis to synthesize codes into meaningful domains. Sites described actions taken to foster patient-centered care in seven domains: 1) leadership; 2) patient and family engagement; 3) staff engagement; 4) focus on innovations; 5) alignment of staff roles and priorities; 6) organizational structures and processes; 7) environment of care. Within each domain, we identified multi-faceted strategies for implementing change. These included efforts by all levels of organizational leaders who modeled patient-centered care in their interactions and fostered willingness to try novel approaches to care amongst staff. Alignment and integration of patient centered care within the organization, particularly surrounding roles, priorities and bureaucratic rules, remained major challenges. Transforming healthcare systems to focus on patient-centered care and better serve the "whole" patient is a complex endeavor. Efforts to transform healthcare culture require robust, multi-pronged efforts at all levels of the organization; leadership is only the beginning. Challenges remain for incorporating patient-centered approaches in the context of competing priorities and regulations. Through actions within each of the domains, organizations may begin to truly transform to patient-driven care.

  16. Multi-criteria GIS-based siting of transfer station for municipal solid waste: The case of Kumasi Metropolitan Area, Ghana.

    PubMed

    Bosompem, Christian; Stemn, Eric; Fei-Baffoe, Bernard

    2016-10-01

    The increase in the quantity of municipal solid waste generated as a result of population growth in most urban areas has resulted in the difficulty of locating suitable land areas to be used as landfills. To curb this, waste transfer stations are used. The Kumasi Metropolitan Area, even though it has an engineered landfill, is faced with the problem of waste collection from the generation centres to the final disposal site. Thus in this study, multi-criteria decision analysis incorporated into a geographic information system was used to determine potential waste transfer station sites. The key result established 11 sites located within six different sub-metros. This result can be used by decision makers for site selection of the waste transfer stations after taking into account other relevant ecological and economic factors. © The Author(s) 2016.

  17. Effects of organizational complexity and resources on construction site risk.

    PubMed

    Forteza, Francisco J; Carretero-Gómez, Jose M; Sesé, Albert

    2017-09-01

    Our research is aimed at studying the relationship between risk level and organizational complexity and resources on constructions sites. Our general hypothesis is that site complexity increases risk, whereas more resources of the structure decrease risk. A Structural Equation Model (SEM) approach was adopted to validate our theoretical model. To develop our study, 957 building sites in Spain were visited and assessed in 2003-2009. All needed data were obtained using a specific tool developed by the authors to assess site risk, structure and resources (Construction Sites Risk Assessment Tool, or CONSRAT). This tool operationalizes the variables to fit our model, specifically, via a site risk index (SRI) and 10 organizational variables. Our random sample is composed largely of small building sites with general high levels of risk, moderate complexity, and low resources on site. The model obtained adequate fit, and results showed empirical evidence that the factors of complexity and resources can be considered predictors of site risk level. Consequently, these results can help companies, managers of construction and regulators to identify which organizational aspects should be improved to prevent risks on sites and consequently accidents. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

  18. Data Mining Algorithms for Classification of Complex Biomedical Data

    ERIC Educational Resources Information Center

    Lan, Liang

    2012-01-01

    In my dissertation, I will present my research which contributes to solve the following three open problems from biomedical informatics: (1) Multi-task approaches for microarray classification; (2) Multi-label classification of gene and protein prediction from multi-source biological data; (3) Spatial scan for movement data. In microarray…

  19. Multi-Agent Strategic Modeling in a Specific Environment

    NASA Astrophysics Data System (ADS)

    Gams, Matjaz; Bezek, Andraz

    Multi-agent modeling in ambient intelligence (AmI) is concerned with the following task [19]: How can external observations of multi-agent systems in the ambient be used to analyze, model, and direct agent behavior? The main purpose is to obtain knowledge about acts in the environment thus enabling proper actions of the AmI systems [1]. Analysis of such systems must thus capture complex world state representation and asynchronous agent activities. Instead of studying basic numerical data, researchers often use more complex data structures, such as rules and decision trees. Some methods are extremely useful when characterizing state space, but lack the ability to clearly represent temporal state changes occurred by agent actions. To comprehend simultaneous agent actions and complex changes of state space, most often a combination of graphical and symbolical representation performs better in terms of human understanding and performance.

  20. Spatial organization of multi-enzyme biocatalytic cascades.

    PubMed

    Quin, M B; Wallin, K K; Zhang, G; Schmidt-Dannert, C

    2017-05-23

    Industrial biocatalysis is an economically attractive option for the production of valuable chemicals. Our repertoire of cheap building blocks and commodity target molecules is vastly enhanced by multi-enzyme biocatalytic cascades. In order to achieve suitable titers in complex novel biocatalytic schemes, spatial organization may become necessary to overcome barriers caused by slow or inhibited enzymes as well as instability of biocatalysts. A number of spatial organization strategies are currently available, which could be integrated in the design of complex cascades. These include fusion proteins, immobilization on solid supports, multi-dimensional scaffolding, and encapsulation within vessels. This review article highlights recent advances in cascade biocatalysis, discusses the role of spatial organization in reaction kinetics, and presents some of the currently employed strategies for spatial organization of multi-enzyme cascades.

  1. Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using electrospray ionization with multi-stage tandem mass spectrometry.

    PubMed

    Johnson, Byron S; Burinsky, David J; Burova, Svetlana A; Davis, Roman; Fitzgerald, Russ N; Matsuoka, Richard T

    2012-05-15

    The 2-aminoaniline scaffold is of significant value to the pharmaceutical industry and is embedded in a number of pharmacophores including 2-aminoanilides and benzimidazoles. A novel application of coordination ion spray mass spectrometry (CIS-MS) for interrogating the silver ion (Ag(+)) complexes of a homologous series of these compounds using multi-stage tandem mass spectrometry is described. Unlike the ubiquitous alkali metal ion complexes, Ag(+) complexes of 2-aminoanilides and benzimidazoles were found to yield [M - H](+) ions in significant abundance via gas-phase elimination of the metal hydride (AgH) resulting in unique product ion cascades. Sample introduction was by liquid chromatography with mass spectrometry analysis performed on a hybrid linear ion trap/orbitrap instrument capable of high-resolution measurements. Rigorous structural characterization by multi-stage tandem mass spectrometry using [M +  H](+), [M - H](-) and [M - H](+) precursor ions derived from ESI and CIS experiments was performed for the homologous series of 2-aminoanilide and benzimidazole compounds. A full tabular comparison of structural information resulting from these product ion cascades was produced. Multi-stage tandem mass spectrometry of [M - H](+) ions resulting from Ag(+) complexes of 2-aminoanilides and benzimidazoles in CIS-MS experiments produced unique product ion cascades that exhibited complementary structural information to that obtained from tandem mass spectrometry of [M  +  H](+) and [M - H](-) ions by electrospray ionization (ESI). These observations may be broadly applicable to other compounds that are observed to form Ag(+) complexes and eliminate AgH. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Selective electrochemical reduction of CO2 to CO with a cobalt chlorin complex adsorbed on multi-walled carbon nanotubes in water.

    PubMed

    Aoi, Shoko; Mase, Kentaro; Ohkubo, Kei; Fukuzumi, Shunichi

    2015-06-25

    Electrocatalytic reduction of CO2 occurred efficiently using a glassy carbon electrode modified with a cobalt(II) chlorin complex adsorbed on multi-walled carbon nanotubes at an applied potential of -1.1 V vs. NHE to yield CO with a Faradaic efficiency of 89% with hydrogen production accounting for the remaining 11% at pH 4.6.

  3. Nonlinear dynamics of the complex multi-scale network

    NASA Astrophysics Data System (ADS)

    Makarov, Vladimir V.; Kirsanov, Daniil; Goremyko, Mikhail; Andreev, Andrey; Hramov, Alexander E.

    2018-04-01

    In this paper, we study the complex multi-scale network of nonlocally coupled oscillators for the appearance of chimera states. Chimera is a special state in which, in addition to the asynchronous cluster, there are also completely synchronous parts in the system. We show that the increase of nodes in subgroups leads to the destruction of the synchronous interaction within the common ring and to the narrowing of the chimera region.

  4. Stability and structural properties of gene regulation networks with coregulation rules.

    PubMed

    Warrell, Jonathan; Mhlanga, Musa

    2017-05-07

    Coregulation of the expression of groups of genes has been extensively demonstrated empirically in bacterial and eukaryotic systems. Such coregulation can arise through the use of shared regulatory motifs, which allow the coordinated expression of modules (and module groups) of functionally related genes across the genome. Coregulation can also arise through the physical association of multi-gene complexes through chromosomal looping, which are then transcribed together. We present a general formalism for modeling coregulation rules in the framework of Random Boolean Networks (RBN), and develop specific models for transcription factor networks with modular structure (including module groups, and multi-input modules (MIM) with autoregulation) and multi-gene complexes (including hierarchical differentiation between multi-gene complex members). We develop a mean-field approach to analyse the dynamical stability of large networks incorporating coregulation, and show that autoregulated MIM and hierarchical gene-complex models can achieve greater stability than networks without coregulation whose rules have matching activation frequency. We provide further analysis of the stability of small networks of both kinds through simulations. We also characterize several general properties of the transients and attractors in the hierarchical coregulation model, and show using simulations that the steady-state distribution factorizes hierarchically as a Bayesian network in a Markov Jump Process analogue of the RBN model. Copyright © 2017. Published by Elsevier Ltd.

  5. Generalized model of electromigration with 1:1 (analyte:selector) complexation stoichiometry: part I. Theory.

    PubMed

    Dubský, Pavel; Müllerová, Ludmila; Dvořák, Martin; Gaš, Bohuslav

    2015-03-06

    The model of electromigration of a multivalent weak acidic/basic/amphoteric analyte that undergoes complexation with a mixture of selectors is introduced. The model provides an extension of the series of models starting with the single-selector model without dissociation by Wren and Rowe in 1992, continuing with the monovalent weak analyte/single-selector model by Rawjee, Williams and Vigh in 1993 and that by Lelièvre in 1994, and ending with the multi-selector overall model without dissociation developed by our group in 2008. The new multivalent analyte multi-selector model shows that the effective mobility of the analyte obeys the original Wren and Row's formula. The overall complexation constant, mobility of the free analyte and mobility of complex can be measured and used in a standard way. The mathematical expressions for the overall parameters are provided. We further demonstrate mathematically that the pH dependent parameters for weak analytes can be simply used as an input into the multi-selector overall model and, in reverse, the multi-selector overall parameters can serve as an input into the pH-dependent models for the weak analytes. These findings can greatly simplify the rationale method development in analytical electrophoresis, specifically enantioseparations. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Characterization of selected cellulolytic activities of multi-enzymatic complex system from Penicillium funiculosum.

    PubMed

    Karboune, Salwa; Geraert, Pierre-André; Kermasha, Selim

    2008-02-13

    The presence of endo-1,4-beta-D-glucanase, cellobiohydrolase, and beta-glucosidase activities in a multi-enzymatic complex system from Penicillium funiculosum was investigated. The interesting feature of these enzymes is their synergistic action for the hydrolysis of the native cellulose into glucose units. Both endo-1,4-beta-D-glucanase and cellobiohydrolase showed broader pH activity profiles, with pH optima of 4.0 and 4.0-5.0, respectively. However, beta-glucosidase activity showed a narrow pH-activity profile, with an optimum pH of 4.5. The different cellulolytic activities were stable in the acidic pH range of 2.5-6.0 and showed a similar optimal temperature of 60 degrees C. Although beta-glucosidase has shown a close catalytic efficiency as that of endo-1,4-beta-D-glucanase, its thermal stability was lower. However, the thermal stability profile of cellobiohydrolase was close to that of endo-1,4-beta-D-glucanase. The results also revealed the presence of high levels of endo-1,3-1,4-beta-D-glucanase, endo-1,3-beta- d-glucanase, and pectinase activities in the multi-enzymatic cellulolytic complex system. Moreover, the investigated multi-enzymatic complex system was effective in degrading the nonstarch polysaccharides of soybean meal.

  7. An Approach for Autonomy: A Collaborative Communication Framework for Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Dufrene, Warren Russell, Jr.

    2005-01-01

    Research done during the last three years has studied the emersion properties of Complex Adaptive Systems (CAS). The deployment of Artificial Intelligence (AI) techniques applied to remote Unmanned Aerial Vehicles has led the author to investigate applications of CAS within the field of Autonomous Multi-Agent Systems. The core objective of current research efforts is focused on the simplicity of Intelligent Agents (IA) and the modeling of these agents within complex systems. This research effort looks at the communication, interaction, and adaptability of multi-agents as applied to complex systems control. The embodiment concept applied to robotics has application possibilities within multi-agent frameworks. A new framework for agent awareness within a virtual 3D world concept is possible where the vehicle is composed of collaborative agents. This approach has many possibilities for applications to complex systems. This paper describes the development of an approach to apply this virtual framework to the NASA Goddard Space Flight Center (GSFC) tetrahedron structure developed under the Autonomous Nano Technology Swarm (ANTS) program and the Super Miniaturized Addressable Reconfigurable Technology (SMART) architecture program. These projects represent an innovative set of novel concepts deploying adaptable, self-organizing structures composed of many tetrahedrons. This technology is pushing current applied Agents Concepts to new levels of requirements and adaptability.

  8. Noninvasive Imaging of Three-dimensional Cardiac Activation Sequence during Pacing and Ventricular Tachycardia

    PubMed Central

    Han, Chengzong; Pogwizd, Steven M.; Killingsworth, Cheryl R.; He, Bin

    2011-01-01

    Background Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. Objective This study aims to rigorously assess the imaging performance of a three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE) induced ventricular tachycardia (VT) in the rabbit heart. Methods Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computer tomography images were obtained to construct geometry model. Results The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72±0.04, and a relative error of 0.30±0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from imaged site of initial activation to pacing site or site of arrhythmias determined from intra-cardiac mapping was ~5mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. Conclusion 3-DCEI can non-invasively delineate important features of focal or multi-focal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequence of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. PMID:21397046

  9. Sensing vascularization of ex-vivo produced oral mucosal equivalent (EVPOME) skin grafts in nude mice using optical spectroscopy

    NASA Astrophysics Data System (ADS)

    Vishwanath, Karthik; Gurjar, Rajan; Kuo, Shiuhyang; Fasi, Anthony; Kim, Roderick; Riccardi, Suzannah; Feinberg, Stephen E.; Wolf, David E.

    2014-03-01

    Repair of soft tissue defects of the lips as seen in complex maxillofacial injuries, requires pre-vascularized multi-tissue composite grafts. Protocols for fabrication of human ex-vivo produced oral mucosal equivalents (EVPOME) composed of epithelial cells and a dermal equivalent are available to create prelaminated flaps for grafting in patients. However, invivo assessment of neovascularization of the buried prelaminated flaps remains clinically challenging. Here, we use diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to non-invasively quantify longitudinal changes in the vessel density and blood-flow within EVPOME grafts implanted in the backs of SCID mice and subsequently to determine the utility of these optical techniques for assessing vascularization of implanted grafts. 20 animals were implanted with EVPOME grafts (1x1x0.05 cm3) in their backs. DRS and DCS measurements were obtained from each animal both atop the graft site and far away from the graft site, at one week post-implantation, each week, for four consecutive weeks. DRS spectra were analyzed using an inverse Monte Carlo model to extract tissue absorption and scattering coefficients, which were then used to extract blood flow information by fitting the experimental DCS traces. There were clear differences in the mean optical parameters (averaged across all mice) at the graft site vs. the off-site measurements. Both the total hemoglobin concentration (from DRS) and the relative blood flow (from DCS) peaked at week 3 at the graft site and declined to the off-site values by week 4. The optical parameters remained relatively constant throughout 4 weeks for the off-site measurements.

  10. A decision support tool for landfill methane generation and gas collection.

    PubMed

    Emkes, Harriet; Coulon, Frédéric; Wagland, Stuart

    2015-09-01

    This study presents a decision support tool (DST) to enhance methane generation at individual landfill sites. To date there is no such tool available to provide landfill decision makers with clear and simplified information to evaluate biochemical processes within a landfill site, to assess performance of gas production and to identify potential remedies to any issues. The current lack in understanding stems from the complexity of the landfill waste degradation process. Two scoring sets for landfill gas production performance are calculated with the tool: (1) methane output score which measures the deviation of the actual methane output rate at each site which the prediction generated by the first order decay model LandGEM; and (2) landfill gas indicators' score, which measures the deviation of the landfill gas indicators from their ideal ranges for optimal methane generation conditions. Landfill gas indicators include moisture content, temperature, alkalinity, pH, BOD, COD, BOD/COD ratio, ammonia, chloride, iron and zinc. A total landfill gas indicator score is provided using multi-criteria analysis to calculate the sum of weighted scores for each indicator. The weights for each indicator are calculated using an analytical hierarchical process. The tool is tested against five real scenarios for landfill sites in UK with a range of good, average and poor landfill methane generation over a one year period (2012). An interpretation of the results is given for each scenario and recommendations are highlighted for methane output rate enhancement. Results demonstrate how the tool can help landfill managers and operators to enhance their understanding of methane generation at a site-specific level, track landfill methane generation over time, compare and rank sites, and identify problems areas within a landfill site. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. iLoc-Animal: a multi-label learning classifier for predicting subcellular localization of animal proteins.

    PubMed

    Lin, Wei-Zhong; Fang, Jian-An; Xiao, Xuan; Chou, Kuo-Chen

    2013-04-05

    Predicting protein subcellular localization is a challenging problem, particularly when query proteins have multi-label features meaning that they may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing methods can only be used to deal with the single-label proteins. Actually, multi-label proteins should not be ignored because they usually bear some special function worthy of in-depth studies. By introducing the "multi-label learning" approach, a new predictor, called iLoc-Animal, has been developed that can be used to deal with the systems containing both single- and multi-label animal (metazoan except human) proteins. Meanwhile, to measure the prediction quality of a multi-label system in a rigorous way, five indices were introduced; they are "Absolute-True", "Absolute-False" (or Hamming-Loss"), "Accuracy", "Precision", and "Recall". As a demonstration, the jackknife cross-validation was performed with iLoc-Animal on a benchmark dataset of animal proteins classified into the following 20 location sites: (1) acrosome, (2) cell membrane, (3) centriole, (4) centrosome, (5) cell cortex, (6) cytoplasm, (7) cytoskeleton, (8) endoplasmic reticulum, (9) endosome, (10) extracellular, (11) Golgi apparatus, (12) lysosome, (13) mitochondrion, (14) melanosome, (15) microsome, (16) nucleus, (17) peroxisome, (18) plasma membrane, (19) spindle, and (20) synapse, where many proteins belong to two or more locations. For such a complicated system, the outcomes achieved by iLoc-Animal for all the aforementioned five indices were quite encouraging, indicating that the predictor may become a useful tool in this area. It has not escaped our notice that the multi-label approach and the rigorous measurement metrics can also be used to investigate many other multi-label problems in molecular biology. As a user-friendly web-server, iLoc-Animal is freely accessible to the public at the web-site .

  12. Identification of a Novel Allosteric Inhibitory Site on Tryptophan Hydroxylase 1 Enabling Unprecedented Selectivity Over all Related Hydroxylases

    PubMed Central

    Petrassi, Mike; Barber, Rob; Be, Celine; Beach, Sarah; Cox, Brian; D’Souza, Anne-Marie; Duggan, Nick; Hussey, Martin; Fox, Roy; Hunt, Peter; Jarai, Gabor; Kosaka, Takatoshi; Oakley, Paul; Patel, Viral; Press, Neil; Rowlands, David; Scheufler, Clemens; Schmidt, Oliver; Srinivas, Honnappa; Turner, Mary; Turner, Rob; Westwick, John; Wolfreys, Alison; Pathan, Nuzhat; Watson, Simon; Thomas, Matthew

    2017-01-01

    Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements – SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition. However, selectivity over non-pathogenic enzyme family members, TPH2, phenylalanine hydroxylase, and tyrosine hydroxylase has hampered therapeutic development. Here we describe the site/sequence, biochemical, and biophysical characterization of a novel allosteric site on TPH1 through which selectivity over TPH2 and related aromatic amino acid hydroxylases is achieved. We demonstrate the mechanism of action by which novel compounds selectively inhibit TPH1 using surface plasma resonance and enzyme competition assays with both tryptophan ligand and BH4 co-factor. We demonstrate 15-fold greater potency within a human carcinoid cell line versus the most potent known TPH1/2 non-specific inhibitor. Lastly, we detail a novel canine in vivo system utilized to determine effective biologic inhibition of newly synthesized 5-HT. These findings are the first to demonstrate TPH1-selective inhibition and may pave the way to a truly effective means to reduce pathologic 5-HT and thereby treat complex remodeling diseases such as PAH. PMID:28529483

  13. Towards large scale multi-target tracking

    NASA Astrophysics Data System (ADS)

    Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

    2014-06-01

    Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

  14. Grain-Size Based Additivity Models for Scaling Multi-rate Uranyl Surface Complexation in Subsurface Sediments

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

    Zhang, Xiaoying; Liu, Chongxuan; Hu, Bill X.

    This study statistically analyzed a grain-size based additivity model that has been proposed to scale reaction rates and parameters from laboratory to field. The additivity model assumed that reaction properties in a sediment including surface area, reactive site concentration, reaction rate, and extent can be predicted from field-scale grain size distribution by linearly adding reaction properties for individual grain size fractions. This study focused on the statistical analysis of the additivity model with respect to reaction rate constants using multi-rate uranyl (U(VI)) surface complexation reactions in a contaminated sediment as an example. Experimental data of rate-limited U(VI) desorption in amore » stirred flow-cell reactor were used to estimate the statistical properties of multi-rate parameters for individual grain size fractions. The statistical properties of the rate constants for the individual grain size fractions were then used to analyze the statistical properties of the additivity model to predict rate-limited U(VI) desorption in the composite sediment, and to evaluate the relative importance of individual grain size fractions to the overall U(VI) desorption. The result indicated that the additivity model provided a good prediction of the U(VI) desorption in the composite sediment. However, the rate constants were not directly scalable using the additivity model, and U(VI) desorption in individual grain size fractions have to be simulated in order to apply the additivity model. An approximate additivity model for directly scaling rate constants was subsequently proposed and evaluated. The result found that the approximate model provided a good prediction of the experimental results within statistical uncertainty. This study also found that a gravel size fraction (2-8mm), which is often ignored in modeling U(VI) sorption and desorption, is statistically significant to the U(VI) desorption in the sediment.« less

  15. Incorporating evolution of transcription factor binding sites into annotated alignments.

    PubMed

    Bais, Abha S; Grossmann, Stefen; Vingron, Martin

    2007-08-01

    Identifying transcription factor binding sites (TFBSs) is essential to elucidate putative regulatory mechanisms. A common strategy is to combine cross-species conservation with single sequence TFBS annotation to yield "conserved TFBSs". Most current methods in this field adopt a multi-step approach that segregates the two aspects. Again, it is widely accepted that the evolutionary dynamics of binding sites differ from those of the surrounding sequence. Hence, it is desirable to have an approach that explicitly takes this factor into account. Although a plethora of approaches have been proposed for the prediction of conserved TFBSs, very few explicitly model TFBS evolutionary properties, while additionally being multi-step. Recently, we introduced a novel approach to simultaneously align and annotate conserved TFBSs in a pair of sequences. Building upon the standard Smith-Waterman algorithm for local alignments, SimAnn introduces additional states for profiles to output extended alignments or annotated alignments. That is, alignments with parts annotated as gaplessly aligned TFBSs (pair-profile hits)are generated. Moreover,the pair- profile related parameters are derived in a sound statistical framework. In this article, we extend this approach to explicitly incorporate evolution of binding sites in the SimAnn framework. We demonstrate the extension in the theoretical derivations through two position-specific evolutionary models, previously used for modelling TFBS evolution. In a simulated setting, we provide a proof of concept that the approach works given the underlying assumptions,as compared to the original work. Finally, using a real dataset of experimentally verified binding sites in human-mouse sequence pairs,we compare the new approach (eSimAnn) to an existing multi-step tool that also considers TFBS evolution. Although it is widely accepted that binding sites evolve differently from the surrounding sequences, most comparative TFBS identification methods do not explicitly consider this.Additionally, prediction of conserved binding sites is carried out in a multi-step approach that segregates alignment from TFBS annotation. In this paper, we demonstrate how the simultaneous alignment and annotation approach of SimAnn can be further extended to incorporate TFBS evolutionary relationships. We study how alignments and binding site predictions interplay at varying evolutionary distances and for various profile qualities.

  16. Plasmonic bio-sensing for the Fenna-Matthews-Olson complex

    NASA Astrophysics Data System (ADS)

    Chen, Guang-Yin; Lambert, Neill; Shih, Yen-An; Liu, Meng-Han; Chen, Yueh-Nan; Nori, Franco

    2017-01-01

    We study theoretically the bio-sensing capabilities of metal nanowire surface plasmons. As a specific example, we couple the nanowire to specific sites (bacteriochlorophyll) of the Fenna-Matthews-Olson (FMO) photosynthetic pigment protein complex. In this hybrid system, we find that when certain sites of the FMO complex are subject to either the suppression of inter-site transitions or are entirely disconnected from the complex, the resulting variations in the excitation transfer rates through the complex can be monitored through the corresponding changes in the scattering spectra of the incident nanowire surface plasmons. We also find that these changes can be further enhanced by changing the ratio of plasmon-site couplings. The change of the Fano lineshape in the scattering spectra further reveals that “site 5” in the FMO complex plays a distinct role from other sites. Our results provide a feasible way, using single photons, to detect mutation-induced, or bleaching-induced, local defects or modifications of the FMO complex, and allows access to both the local and global properties of the excitation transfer in such systems.

  17. The MPLEx Protocol for Multi-omic Analyses of Soil Samples

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

    Nicora, Carrie D.; Burnum-Johnson, Kristin E.; Nakayasu, Ernesto S.

    Mass spectrometry (MS)-based integrated metaproteomic, metabolomic and lipidomic (multi-omic) studies are transforming our ability to understand and characterize microbial communities in environmental and biological systems. These measurements are even enabling enhanced analyses of complex soil microbial communities, which are the most complex microbial systems known to date. Multi-omic analyses, however, do have sample preparation challenges since separate extractions are typically needed for each omic study, thereby greatly amplifying the preparation time and amount of sample required. To address this limitation, a 3-in-1 method for simultaneous metabolite, protein, and lipid extraction (MPLEx) from the exact same soil sample was created bymore » adapting a solvent-based approach. This MPLEx protocol has proven to be simple yet robust for many sample types and even when utilized for limited quantities of complex soil samples. The MPLEx method also greatly enabled the rapid multi-omic measurements needed to gain a better understanding of the members of each microbial community, while evaluating the changes taking place upon biological and environmental perturbations.« less

  18. Model-based MPC enables curvilinear ILT using either VSB or multi-beam mask writers

    NASA Astrophysics Data System (ADS)

    Pang, Linyong; Takatsukasa, Yutetsu; Hara, Daisuke; Pomerantsev, Michael; Su, Bo; Fujimura, Aki

    2017-07-01

    Inverse Lithography Technology (ILT) is becoming the choice for Optical Proximity Correction (OPC) of advanced technology nodes in IC design and production. Multi-beam mask writers promise significant mask writing time reduction for complex ILT style masks. Before multi-beam mask writers become the main stream working tools in mask production, VSB writers will continue to be the tool of choice to write both curvilinear ILT and Manhattanized ILT masks. To enable VSB mask writers for complex ILT style masks, model-based mask process correction (MB-MPC) is required to do the following: 1). Make reasonable corrections for complex edges for those features that exhibit relatively large deviations from both curvilinear ILT and Manhattanized ILT designs. 2). Control and manage both Edge Placement Errors (EPE) and shot count. 3. Assist in easing the migration to future multi-beam mask writer and serve as an effective backup solution during the transition. In this paper, a solution meeting all those requirements, MB-MPC with GPU acceleration, will be presented. One model calibration per process allows accurate correction regardless of the target mask writer.

  19. Expansion of the gateway multisite recombination cloning toolkit.

    PubMed

    Shearin, Harold K; Dvarishkis, Alisa R; Kozeluh, Craig D; Stowers, R Steven

    2013-01-01

    Precise manipulation of transgene expression in genetic model organisms has led to advances in understanding fundamental mechanisms of development, physiology, and genetic disease. Transgene construction is, however, a precondition of transgene expression, and often limits the rate of experimental progress. Here we report an expansion of the modular Gateway MultiSite recombination-cloning platform for high efficiency transgene assembly. The expansion includes two additional destination vectors and entry clones for the LexA binary transcription system, among others. These new tools enhance the expression levels possible with Gateway MultiSite generated transgenes and make possible the generation of LexA drivers and reporters with Gateway MultiSite cloning. In vivo data from transgenic Drosophila functionally validating each novel component are presented and include neuronal LexA drivers, LexAop2 red and green fluorescent synaptic vesicle reporters, TDC2 and TRH LexA, GAL4, and QF drivers, and LexAop2, UAS, and QUAS channelrhodopsin2 T159C reporters.

  20. Sediment Contaminants and Infauna Associated with Recreational Boating Structures in a Multi-Use Marine Park.

    PubMed

    Sim, Vivian X Y; Dafforn, Katherine A; Simpson, Stuart L; Kelaher, Brendan P; Johnston, Emma L

    2015-01-01

    Multi-use marine parks achieve conservation through spatial management of activities. Zoning of marine parks in New South Wales, Australia, includes high conservation areas and special purpose zones (SPZ) where maritime activities are concentrated. Although such measures geographically constrain anthropogenic impacts, we have limited understanding of potential ecological effects. We assessed sediment communities and contaminants adjacent to boating infrastructure (boat ramps, jetties and a marina) in a SPZ from the Clyde Estuary in Batemans Marine Park. Metal concentrations and fines content were elevated at boating structures compared to reference sites. Species richness was higher at sites with boating structures, where capitellid polychaetes and nematodes dominated the communities. Changes associated with boating structures were localised and did not extend beyond breakwalls or to reference sites outside the SPZ. The study highlights the benefits of appropriate zoning in a multi-use marine park and the potential to minimise stress on pristine areas through the application of spatial management.

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