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Sample records for model identifies key

  1. Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

    Science.gov (United States)

    Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

    2014-01-01

    Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

  2. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

    2014-07-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  3. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  4. Using Range-Wide Abundance Modeling to Identify Key Conservation Areas for the Micro-Endemic Bolson Tortoise (Gopherus flavomarginatus.

    Directory of Open Access Journals (Sweden)

    Cinthya A Ureña-Aranda

    Full Text Available A widespread biogeographic pattern in nature is that population abundance is not uniform across the geographic range of species: most occurrence sites have relatively low numbers, whereas a few places contain orders of magnitude more individuals. The Bolson tortoise Gopherus flavomarginatus is endemic to a small region of the Chihuahuan Desert in Mexico, where habitat deterioration threatens this species with extinction. In this study we combined field burrows counts and the approach for modeling species abundance based on calculating the distance to the niche centroid to obtain range-wide abundance estimates. For the Bolson tortoise, we found a robust, negative relationship between observed burrows abundance and distance to the niche centroid, with a predictive capacity of 71%. Based on these results we identified four priority areas for the conservation of this microendemic and threatened tortoise. We conclude that this approach may be a useful approximation for identifying key areas for sampling and conservation efforts in elusive and rare species.

  5. Identifying key processes in the hydrochemistry of a basin through the combined use of factor and regression models

    Indian Academy of Sciences (India)

    Sandow Mark Yidana; Bruce Banoeng-Yakubo; Patrick Asamoah Sakyi

    2012-04-01

    An innovative technique of measuring the intensities of major sources of variation in the hydrochemistry of (ground) water in a basin has been developed. This technique, which is based on the combination of R-mode factor and multiple regression analyses, can be used to measure the degrees of influence of the major sources of variation in the hydrochemistry without measuring the concentrations of the entire set of physico-chemical parameters which are often used to characterize water systems. R-mode factor analysis was applied to the data of 13 physico-chemical parameters and 50 samples in order to determine the major sources of variation in the hydrochemistry of some aquifers in the western region of Ghana. In this study, three sources of variation in the hydrochemistry were distinguished: the dissolution of chlorides and sulfates of the major cations, carbonate mineral dissolution, and silicate mineral weathering. Two key parameters were identified with each of the processes and multiple regression models were developed for each process. These models were tested and found to predict these processes quite accurately, and can be applied anywhere within the terrain. This technique can be reliably applied in areas where logistical constraints limit water sampling for whole basin hydrochemical characterization. Q-mode hierarchical cluster analysis (HCA) applied to the data revealed three major groundwater associations distinguished on the basis of the major causes of variation in the hydrochemistry. The three groundwater types represent Na–HCO3, Ca–HCO3, and Na–Cl groundwater types. Silicate stability diagrams suggest that all these groundwater types are mainly stable in the kaolinite and montmorillonite fields suggesting moderately restricted flow conditions.

  6. IDENTIFYING KEY CONTRIBUTIONS TO INFORMATION SCIENCE,

    Science.gov (United States)

    Several alternative approaches were examined to determine how one might identify some of the key (written) contributions to ’ information science ’. The...references. The unclear selective patterns in current bibliographies in the information science field also present problems. It is suggested that in...identifying key contributions we are far from common agreement on the conceptual, methodological or practical contributions to the information science field

  7. Midwifery-led antenatal care models: mapping a systematic review to an evidence-based quality framework to identify key components and characteristics of care

    OpenAIRE

    Symon, A; J. Pringle; Cheyne, H.; Downe, S.; Hundley, Vanora; Lee, E; Lynn, F; McFadden, A.; McNeill, J.; Renfrew, M. J.; Ross-Davie, M.; Van Teijlingen, Edwin; Whitford, H.; Alderdice, F.

    2016-01-01

    Background: Implementing effective antenatal care models is a key global policy goal. However, the mechanisms of action of these multi-faceted models that would allow widespread implementation are seldom examined and poorly understood. In existing care model analyses there is little distinction between what is done, how it is done, and who does it. A new evidence-informed quality maternal and newborn care (QMNC) framework identifies key characteristics of quality care. This offers the opportu...

  8. A systems toxicology approach identifies Lyn as a key signaling phosphoprotein modulated by mercury in a B lymphocyte cell model

    Energy Technology Data Exchange (ETDEWEB)

    Caruso, Joseph A.; Stemmer, Paul M. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Dombkowski, Alan [Department of Pediatrics, Wayne State University, Detroit, MI (United States); Caruthers, Nicholas J. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States); Rosenspire, Allen J., E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States)

    2014-04-01

    Network and protein–protein interaction analyses of proteins undergoing Hg{sup 2+}-induced phosphorylation and dephosphorylation in Hg{sup 2+}-intoxicated mouse WEHI-231 B cells identified Lyn as the most interconnected node. Lyn is a Src family protein tyrosine kinase known to be intimately involved in the B cell receptor (BCR) signaling pathway. Under normal signaling conditions the tyrosine kinase activity of Lyn is controlled by phosphorylation, primarily of two well known canonical regulatory tyrosine sites, Y-397 and Y-508. However, Lyn has several tyrosine residues that have not yet been determined to play a major role under normal signaling conditions, but are potentially important sites for phosphorylation following mercury exposure. In order to determine how Hg{sup 2+} exposure modulates the phosphorylation of additional residues in Lyn, a targeted MS assay was developed. Initial mass spectrometric surveys of purified Lyn identified 7 phosphorylated tyrosine residues. A quantitative assay was developed from these results using the multiple reaction monitoring (MRM) strategy. WEHI-231 cells were treated with Hg{sup 2+}, pervanadate (a phosphatase inhibitor), or anti-Ig antibody (to stimulate the BCR). Results from these studies showed that the phosphoproteomic profile of Lyn after exposure of the WEHI-231 cells to a low concentration of Hg{sup 2+} closely resembled that of anti-Ig antibody stimulation, whereas exposure to higher concentrations of Hg{sup 2+} led to increases in the phosphorylation of Y-193/Y-194, Y-501 and Y-508 residues. These data indicate that mercury can disrupt a key regulatory signal transduction pathway in B cells and point to phospho-Lyn as a potential biomarker for mercury exposure. - Highlights: • Inorganic mercury (Hg{sup 2+}) induces changes in the WEHI-231 B cell phosphoproteome. • The B cell receptor (BCR) signaling pathway was the pathway most affected by Hg{sup 2+}. • The Src family phosphoprotein kinase Lyn was the

  9. Identifying key odorants from animal feeding operations

    Science.gov (United States)

    Odor emissions from animal agriculutre negatively impact air qualitly in surrounding communities. Current analytical practices are biased against agriculutral odorants and thus inadequate for odor quantification. The purpose of this study was to evaluate two different techniques ability to identify ...

  10. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  11. Generalized Linear Models to Identify Key Hydromorphological and Chemical Variables Determining the Occurrence of Macroinvertebrates in the Guayas River Basin (Ecuador

    Directory of Open Access Journals (Sweden)

    Minar Naomi Damanik-Ambarita

    2016-07-01

    Full Text Available The biotic integrity of the Guayas River basin in Ecuador is at environmental risk due to extensive anthropogenic activities. We investigated the potential impacts of hydromorphological and chemical variables on biotic integrity using macroinvertebrate-based bioassessments. The bioassessment methods utilized included the Biological Monitoring Working Party adapted for Colombia (BMWP-Col and the average score per taxon (ASPT, via an extensive sampling campaign that was completed throughout the river basin at 120 sampling sites. The BMWP-Col classification ranged from very bad to good, and from probable severe pollution to clean water based on the ASPT scores. Generalized linear models (GLMs and sensitivity analysis were used to relate the bioassessment index to hydromorphological and chemical variables. It was found that elevation, nitrate-N, sediment angularity, logs, presence of macrophytes, flow velocity, turbidity, bank shape, land use and chlorophyll were the key environmental variables affecting the BMWP-Col. From the analyses, it was observed that the rivers at the upstream higher elevations of the river basin were in better condition compared to lowland systems and that a higher flow velocity was linked to a better BMWP-Col score. The nitrate concentrations were very low in the entire river basin and did not relate to a negative impact on the macroinvertebrate communities. Although the results of the models provided insights into the ecosystem, cross fold model development and validation also showed that there was a level of uncertainty in the outcomes. However, the results of the models and sensitivity analysis can support water management actions to determine and focus on alterable variables, such as the land use at different elevations, monitoring of nitrate and chlorophyll concentrations, macrophyte presence, sediment transport and bank stability.

  12. A free-access online key to identify Amazonian ferns

    Directory of Open Access Journals (Sweden)

    Gabriela Zuquim

    2017-03-01

    Full Text Available There is urgent need for more data on species distributions in order to improve conservation planning. A crucial but challenging aspect of producing high-quality data is the correct identification of organisms. Traditional printed floras and dichotomous keys are difficult to use for someone not familiar with the technical jargon. In poorly known areas, such as Amazonia, they also become quickly outdated as new species are described or ranges extended. Recently, online tools have allowed developing dynamic, interactive, and accessible keys that make species identification possible for a broader public. In order to facilitate identifying plants collected in field inventories, we developed an internet-based free-access tool to identify Amazonian fern species. We focused on ferns, because they are easy to collect and their edaphic affinities are relatively well known, so they can be used as an indicator group for habitat mapping. Our key includes 302 terrestrial and aquatic entities mainly from lowland Amazonian forests. It is a free-access key, so the user can freely choose which morphological features to use and in which order to assess them. All taxa are richly illustrated, so specimens can be identified by a combination of character choices, visual comparison, and written descriptions. The identification tool was developed in Lucid 3.5 software and it is available at http://keyserver.lucidcentral.org:8080/sandbox/keys.jsp.

  13. Identifying key hospital service quality factors in online health communities.

    Science.gov (United States)

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

    2015-04-07

    The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

  14. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  15. Identifying the Key Concerns of Irish Persons with Intellectual Disability

    Science.gov (United States)

    García Iriarte, Edurne; O'Brien, Patricia; McConkey, Roy; Wolfe, Marie; O'Doherty, Siobhain

    2014-01-01

    Background: Internationally, people with intellectual disability are socially marginalized, and their rights under the United Nations Convention for the Rights of Persons with Disabilities (CRPD) are often ignored. Aims: This paper aims to define the key concerns of adults with an intellectual disability in relation to their participation in…

  16. Soil fauna: key to new carbon models

    Science.gov (United States)

    Filser, Juliane; Faber, Jack H.; Tiunov, Alexei V.; Brussaard, Lijbert; Frouz, Jan; De Deyn, Gerlinde; Uvarov, Alexei V.; Berg, Matty P.; Lavelle, Patrick; Loreau, Michel; Wall, Diana H.; Querner, Pascal; Eijsackers, Herman; José Jiménez, Juan

    2016-11-01

    Soil organic matter (SOM) is key to maintaining soil fertility, mitigating climate change, combatting land degradation, and conserving above- and below-ground biodiversity and associated soil processes and ecosystem services. In order to derive management options for maintaining these essential services provided by soils, policy makers depend on robust, predictive models identifying key drivers of SOM dynamics. Existing SOM models and suggested guidelines for future SOM modelling are defined mostly in terms of plant residue quality and input and microbial decomposition, overlooking the significant regulation provided by soil fauna. The fauna controls almost any aspect of organic matter turnover, foremost by regulating the activity and functional composition of soil microorganisms and their physical-chemical connectivity with soil organic matter. We demonstrate a very strong impact of soil animals on carbon turnover, increasing or decreasing it by several dozen percent, sometimes even turning C sinks into C sources or vice versa. This is demonstrated not only for earthworms and other larger invertebrates but also for smaller fauna such as Collembola. We suggest that inclusion of soil animal activities (plant residue consumption and bioturbation altering the formation, depth, hydraulic properties and physical heterogeneity of soils) can fundamentally affect the predictive outcome of SOM models. Understanding direct and indirect impacts of soil fauna on nutrient availability, carbon sequestration, greenhouse gas emissions and plant growth is key to the understanding of SOM dynamics in the context of global carbon cycling models. We argue that explicit consideration of soil fauna is essential to make realistic modelling predictions on SOM dynamics and to detect expected non-linear responses of SOM dynamics to global change. We present a decision framework, to be further developed through the activities of KEYSOM, a European COST Action, for when mechanistic SOM models

  17. Identifying the Key Weaknesses in Network Security at Colleges.

    Science.gov (United States)

    Olsen, Florence

    2000-01-01

    A new study identifies and ranks the 10 security gaps responsible for most outsider attacks on college computer networks. The list is intended to help campus system administrators establish priorities as they work to increase security. One network security expert urges that institutions utilize multiple security layers. (DB)

  18. Identifying key nodes in multilayer networks based on tensor decomposition

    Science.gov (United States)

    Wang, Dingjie; Wang, Haitao; Zou, Xiufen

    2017-06-01

    The identification of essential agents in multilayer networks characterized by different types of interactions is a crucial and challenging topic, one that is essential for understanding the topological structure and dynamic processes of multilayer networks. In this paper, we use the fourth-order tensor to represent multilayer networks and propose a novel method to identify essential nodes based on CANDECOMP/PARAFAC (CP) tensor decomposition, referred to as the EDCPTD centrality. This method is based on the perspective of multilayer networked structures, which integrate the information of edges among nodes and links between different layers to quantify the importance of nodes in multilayer networks. Three real-world multilayer biological networks are used to evaluate the performance of the EDCPTD centrality. The bar chart and ROC curves of these multilayer networks indicate that the proposed approach is a good alternative index to identify real important nodes. Meanwhile, by comparing the behavior of both the proposed method and the aggregated single-layer methods, we demonstrate that neglecting the multiple relationships between nodes may lead to incorrect identification of the most versatile nodes. Furthermore, the Gene Ontology functional annotation demonstrates that the identified top nodes based on the proposed approach play a significant role in many vital biological processes. Finally, we have implemented many centrality methods of multilayer networks (including our method and the published methods) and created a visual software based on the MATLAB GUI, called ENMNFinder, which can be used by other researchers.

  19. Identifying key conservation threats to Alpine birds through expert knowledge.

    Science.gov (United States)

    Chamberlain, Dan E; Pedrini, Paolo; Brambilla, Mattia; Rolando, Antonio; Girardello, Marco

    2016-01-01

    Alpine biodiversity is subject to a range of increasing threats, but the scarcity of data for many taxa means that it is difficult to assess the level and likely future impact of a given threat. Expert opinion can be a useful tool to address knowledge gaps in the absence of adequate data. Experts with experience in Alpine ecology were approached to rank threat levels for 69 Alpine bird species over the next 50 years for the whole European Alps in relation to ten categories: land abandonment, climate change, renewable energy, fire, forestry practices, grazing practices, hunting, leisure, mining and urbanization. There was a high degree of concordance in ranking of perceived threats among experts for most threat categories. The major overall perceived threats to Alpine birds identified through expert knowledge were land abandonment, urbanization, leisure and forestry, although other perceived threats were ranked highly for particular species groups (renewable energy and hunting for raptors, hunting for gamebirds). For groups of species defined according to their breeding habitat, open habitat species and treeline species were perceived as the most threatened. A spatial risk assessment tool based on summed scores for the whole community showed threat levels were highest for bird communities of the northern and western Alps. Development of the approaches given in this paper, including addressing biases in the selection of experts and adopting a more detailed ranking procedure, could prove useful in the future in identifying future threats, and in carrying out risk assessments based on levels of threat to the whole bird community.

  20. Identifying key conservation threats to Alpine birds through expert knowledge

    Directory of Open Access Journals (Sweden)

    Dan E. Chamberlain

    2016-02-01

    Full Text Available Alpine biodiversity is subject to a range of increasing threats, but the scarcity of data for many taxa means that it is difficult to assess the level and likely future impact of a given threat. Expert opinion can be a useful tool to address knowledge gaps in the absence of adequate data. Experts with experience in Alpine ecology were approached to rank threat levels for 69 Alpine bird species over the next 50 years for the whole European Alps in relation to ten categories: land abandonment, climate change, renewable energy, fire, forestry practices, grazing practices, hunting, leisure, mining and urbanization. There was a high degree of concordance in ranking of perceived threats among experts for most threat categories. The major overall perceived threats to Alpine birds identified through expert knowledge were land abandonment, urbanization, leisure and forestry, although other perceived threats were ranked highly for particular species groups (renewable energy and hunting for raptors, hunting for gamebirds. For groups of species defined according to their breeding habitat, open habitat species and treeline species were perceived as the most threatened. A spatial risk assessment tool based on summed scores for the whole community showed threat levels were highest for bird communities of the northern and western Alps. Development of the approaches given in this paper, including addressing biases in the selection of experts and adopting a more detailed ranking procedure, could prove useful in the future in identifying future threats, and in carrying out risk assessments based on levels of threat to the whole bird community.

  1. Sparse Linear Identifiable Multivariate Modeling

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2011-01-01

    In this paper we consider sparse and identifiable linear latent variable (factor) and linear Bayesian network models for parsimonious analysis of multivariate data. We propose a computationally efficient method for joint parameter and model inference, and model comparison. It consists of a fully...... Bayesian hierarchy for sparse models using slab and spike priors (two-component δ-function and continuous mixtures), non-Gaussian latent factors and a stochastic search over the ordering of the variables. The framework, which we call SLIM (Sparse Linear Identifiable Multivariate modeling), is validated...... and bench-marked on artificial and real biological data sets. SLIM is closest in spirit to LiNGAM (Shimizu et al., 2006), but differs substantially in inference, Bayesian network structure learning and model comparison. Experimentally, SLIM performs equally well or better than LiNGAM with comparable...

  2. A Model of Hierarchical Key Assignment Scheme

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhigang; ZHAO Jing; XU Maozhi

    2006-01-01

    A model of the hierarchical key assignment scheme is approached in this paper, which can be used with any cryptography algorithm. Besides, the optimal dynamic control property of a hierarchical key assignment scheme will be defined in this paper. Also, our scheme model will meet this property.

  3. On the Use of MCDM Technique for Identifying Key Technology: A case of Auto Company

    National Research Council Canada - National Science Library

    Aliakbar Mazlomi; osnah bt. Mohd. Yusuff

    2011-01-01

    .... Moreover, identifying strategic technology is main part of strategydevelopment. This article tries to apply MCDM methods in finding key strategic technologies from identified technologies from in order to provide appropriate technology strategy...

  4. Classification Models for Symmetric Key Cryptosystem Identification

    Directory of Open Access Journals (Sweden)

    Shri Kant

    2012-01-01

    Full Text Available The present paper deals with the basic principle and theory behind prevalent classification models and their judicious application for symmetric key cryptosystem identification. These techniques have been implemented and verified on varieties of known and simulated data sets. After establishing the techniques the problems of cryptosystem identification have been addressed.Defence Science Journal, 2012, 62(1, pp.38-45, DOI:http://dx.doi.org/10.14429/dsj.62.1440

  5. Key Elements of Effective Teaching in the Direct Teaching Model.

    Science.gov (United States)

    Bruning, Roger H.

    Summaries and outlines are presented of key elements in effective teaching identified in research studies by Kounin (1970), Brophy (1973), Brophy and Evertson (1976), Stallings (1974; l975), Berliner (1979), and Good and Grouws (1979). These elements are synthesized in a direct teaching model that delineates the characteristics of effective…

  6. Identifying Determinants of Organizational Development as the Key Developers of Employee Soft Skill

    Directory of Open Access Journals (Sweden)

    Shahjahan Laghari

    2016-10-01

    Full Text Available The purpose of this article is to identify the determinants of organizational development as the key developers of employee soft skills. Various studies have been taken where determinants of organizational development defining soft skills in employees are discussed. However, the current study is different in Pakistani industry context as the link was missing about the determinants of organizational development which in synchronized way help in developing soft skills in employees of firm. This research uses explanatory approach; incorporating secondary data extracted under the light of existing school of thoughts paired with quantification through data collected from respondents in Pakistani corporate sector. Hypotheses are tested using structural equation model (SEM technique. Results This research showed an affirmative link between determinants of organizational development and development of soft skills in employees. Finally, the study proposes enriching insights on few missing links that can be researched and triggered achieving maximized outcomes.

  7. Identifying the key personnel in a nurse-initiated hospital waste reduction program.

    Science.gov (United States)

    McDermott-Levy, Ruth; Fazzini, Carol

    2010-01-01

    Hospitals in the United States generate more than 6600 tons of trash a day and approximately 85% of the waste is nonhazardous solid waste such as food, cardboard, and plastic. Treatment and management of hospital waste can lead to environmental problems for the communities that receive the waste. One health system's shared governance model provided the foundation to develop a nurse-led hospital waste reduction program that focused on point-of-care waste management. Waste reduction program development required working with a variety of departments within and external to the health system. The interdisciplinary approach informed the development of the waste reduction program. This article identifies the key departments that were necessary to include when developing a hospital waste reduction program.

  8. Identifying key radiogenomic associations between DCE-MRI and micro-RNA expressions for breast cancer

    Science.gov (United States)

    Samala, Ravi K.; Chan, Heang-Ping; Hadjiiski, Lubomir; Helvie, Mark A.; Kim, Renaid

    2017-03-01

    Understanding the key radiogenomic associations for breast cancer between DCE-MRI and micro-RNA expressions is the foundation for the discovery of radiomic features as biomarkers for assessing tumor progression and prognosis. We conducted a study to analyze the radiogenomic associations for breast cancer using the TCGA-TCIA data set. The core idea that tumor etiology is a function of the behavior of miRNAs is used to build the regression models. The associations based on regression are analyzed for three study outcomes: diagnosis, prognosis, and treatment. The diagnosis group consists of miRNAs associated with clinicopathologic features of breast cancer and significant aberration of expression in breast cancer patients. The prognosis group consists of miRNAs which are closely associated with tumor suppression and regulation of cell proliferation and differentiation. The treatment group consists of miRNAs that contribute significantly to the regulation of metastasis thereby having the potential to be part of therapeutic mechanisms. As a first step, important miRNA expressions were identified and their ability to classify the clinical phenotypes based on the study outcomes was evaluated using the area under the ROC curve (AUC) as a figure-of-merit. The key mapping between the selected miRNAs and radiomic features were determined using least absolute shrinkage and selection operator (LASSO) regression analysis within a two-loop leave-one-out cross-validation strategy. These key associations indicated a number of radiomic features from DCE-MRI to be potential biomarkers for the three study outcomes.

  9. Identifying and modeling safety hazards

    Energy Technology Data Exchange (ETDEWEB)

    DANIELS,JESSE; BAHILL,TERRY; WERNER,PAUL W.

    2000-03-29

    The hazard model described in this paper is designed to accept data over the Internet from distributed databases. A hazard object template is used to ensure that all necessary descriptors are collected for each object. Three methods for combining the data are compared and contrasted. Three methods are used for handling the three types of interactions between the hazard objects.

  10. Sparse Linear Identifiable Multivariate Modeling

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2011-01-01

    and bench-marked on artificial and real biological data sets. SLIM is closest in spirit to LiNGAM (Shimizu et al., 2006), but differs substantially in inference, Bayesian network structure learning and model comparison. Experimentally, SLIM performs equally well or better than LiNGAM with comparable...

  11. Identifying Key Performance Indicators for Holistic Hospital Management with a Modified DEMATEL Approach.

    Science.gov (United States)

    Si, Sheng-Li; You, Xiao-Yue; Liu, Hu-Chen; Huang, Jia

    2017-08-19

    Performance analysis is an important way for hospitals to achieve higher efficiency and effectiveness in providing services to their customers. The performance of the healthcare system can be measured by many indicators, but it is difficult to improve them simultaneously due to the limited resources. A feasible way is to identify the central and influential indicators to improve healthcare performance in a stepwise manner. In this paper, we propose a hybrid multiple criteria decision making (MCDM) approach to identify key performance indicators (KPIs) for holistic hospital management. First, through integrating evidential reasoning approach and interval 2-tuple linguistic variables, various assessments of performance indicators provided by healthcare experts are modeled. Then, the decision making trial and evaluation laboratory (DEMATEL) technique is adopted to build an interactive network and visualize the causal relationships between the performance indicators. Finally, an empirical case study is provided to demonstrate the proposed approach for improving the efficiency of healthcare management. The results show that "accidents/adverse events", "nosocomial infection", ''incidents/errors", "number of operations/procedures" are significant influential indicators. Also, the indicators of "length of stay", "bed occupancy" and "financial measures" play important roles in performance evaluation of the healthcare organization. The proposed decision making approach could be considered as a reference for healthcare administrators to enhance the performance of their healthcare institutions.

  12. Ebola Virus Infection Modelling and Identifiability Problems

    Directory of Open Access Journals (Sweden)

    Van-Kinh eNguyen

    2015-04-01

    Full Text Available The recent outbreaks of Ebola virus (EBOV infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4, basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently neededto tackle this lethal disease. Mathematical modelling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modelling approach to unravel the interaction between EBOV and the host cells isstill missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells in EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parametersin viral infections kinetics is the key contribution of this work, paving the way for future modelling work on EBOV infection.

  13. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

    Directory of Open Access Journals (Sweden)

    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  14. Identifying same-cell contours in image stacks: a key step in making 3D reconstructions.

    Science.gov (United States)

    Leung, Tony Kin Shun; Veldhuis, Jim H; Krens, S F Gabby; Heisenberg, C P; Brodland, G Wayne

    2011-02-01

    Identification of contours belonging to the same cell is a crucial step in the analysis of confocal stacks and other image sets in which cell outlines are visible, and it is central to the making of 3D cell reconstructions. When the cells are close packed, the contour grouping problem is more complex than that found in medical imaging, for example, because there are multiple regions of interest, the regions are not separable from each other by an identifiable background and regions cannot be distinguished by intensity differences. Here, we present an algorithm that uses three primary metrics-overlap of contour areas in adjacent images, co-linearity of the centroids of these areas across three images in a stack, and cell taper-to assign cells to groups. Decreasing thresholds are used to successively assign contours whose membership is less obvious. In a final step, remaining contours are assigned to existing groups by setting all thresholds to zero and groups having strong hour-glass shapes are partitioned. When applied to synthetic data from isotropic model aggregates, a curved model epithelium in which the long axes of the cells lie at all possible angles to the transection plane, and a confocal image stack, algorithm assignments were between 97 and 100% accurate in sets having at least four contours per cell. The algorithm is not particularly sensitive to the thresholds used, and a single set of parameters was used for all of the tests. The algorithm, which could be extended to time-lapse data, solves a key problem in the translation of image data into cell information.

  15. Identifying Key Factors for Introducing GPS-Based Fleet Management Systems to the Logistics Industry

    Directory of Open Access Journals (Sweden)

    Yi-Chung Hu

    2015-01-01

    Full Text Available The rise of e-commerce and globalization has changed consumption patterns. Different industries have different logistical needs. In meeting needs with different schedules logistics play a key role. Delivering a seamless service becomes a source of competitive advantage for the logistics industry. Global positioning system-based fleet management system technology provides synergy to transport companies and achieves many management goals such as monitoring and tracking commodity distribution, energy saving, safety, and quality. A case company, which is a subsidiary of a very famous food and retail conglomerate and operates the largest shipping line in Taiwan, has suffered from the nonsmooth introduction of GPS-based fleet management systems in recent years. Therefore, this study aims to identify key factors for introducing related systems to the case company. By using DEMATEL and ANP, we can find not only key factors but also causes and effects among key factors. The results showed that support from executives was the most important criterion but it has the worst performance among key factors. It is found that adequate annual budget planning, enhancement of user intention, and collaboration with consultants with high specialty could be helpful to enhance the faith of top executives for successfully introducing the systems to the case company.

  16. A Provably Secure Revocable ID-Based Authenticated Group Key Exchange Protocol with Identifying Malicious Participants

    Directory of Open Access Journals (Sweden)

    Tsu-Yang Wu

    2014-01-01

    Full Text Available The existence of malicious participants is a major threat for authenticated group key exchange (AGKE protocols. Typically, there are two detecting ways (passive and active to resist malicious participants in AGKE protocols. In 2012, the revocable identity- (ID- based public key system (R-IDPKS was proposed to solve the revocation problem in the ID-based public key system (IDPKS. Afterwards, based on the R-IDPKS, Wu et al. proposed a revocable ID-based AGKE (RID-AGKE protocol, which adopted a passive detecting way to resist malicious participants. However, it needs three rounds and cannot identify malicious participants. In this paper, we fuse a noninteractive confirmed computation technique to propose the first two-round RID-AGKE protocol with identifying malicious participants, which is an active detecting way. We demonstrate that our protocol is a provably secure AGKE protocol with forward secrecy and can identify malicious participants. When compared with the recently proposed ID/RID-AGKE protocols, our protocol possesses better performance and more robust security properties.

  17. Iterative key-residues interrogation of a phytase with thermostability increasing substitutions identified in directed evolution.

    Science.gov (United States)

    Shivange, Amol V; Roccatano, Danilo; Schwaneberg, Ulrich

    2016-01-01

    Bacterial phytases have attracted industrial interest as animal feed supplement due to their high activity and sufficient thermostability (required for feed pelleting). We devised an approach named KeySIDE,  an iterative Key-residues interrogation of the wild type with Substitutions Identified in Directed Evolution for improving Yersinia mollaretii phytase (Ymphytase) thermostability by combining key beneficial substitutions and elucidating their individual roles. Directed evolution yielded in a discovery of nine positions in Ymphytase and combined iteratively to identify key positions. The "best" combination (M6: T77K, Q154H, G187S, and K289Q) resulted in significantly improved thermal resistance; the residual activity improved from 35 % (wild type) to 89 % (M6) at 58 °C and 20-min incubation. Melting temperature increased by 3 °C in M6 without a loss of specific activity. Molecular dynamics simulation studies revealed reduced flexibility in the loops located next to helices (B, F, and K) which possess substitutions (Helix-B: T77K, Helix-F: G187S, and Helix-K: K289E/Q). Reduced flexibility in the loops might be caused by strengthened hydrogen bonding network (e.g., G187S and K289E/K289Q) and a salt bridge (T77K). Our results demonstrate a promising approach to design phytases in food research, and we hope that the KeySIDE might become an attractive approach for understanding of structure-function relationships of enzymes.

  18. RNA-Seq transcriptomic analysis with Bag2D software identifies key pathways enhancing lipid yield in a high lipid-producing mutant of the non-model green alga Dunaliella tertiolecta.

    Science.gov (United States)

    Yao, Lina; Tan, Tin Wee; Ng, Yi-Kai; Ban, Kenneth Hon Kim; Shen, Hui; Lin, Huixin; Lee, Yuan Kun

    2015-01-01

    For many years, increasing demands for fossil fuels have met with limited supply. As a potential substitute and renewable source of biofuel feedstock, microalgae have received significant attention. However, few of the current algal species produce high lipid yields to be commercially viable. To discover more high yielding strains, next-generation sequencing technology is used to elucidate lipid synthetic pathways and energy metabolism involved in lipid yield. When subjected to manipulation by genetic and metabolic engineering, enhancement of such pathways may further enhance lipid yield. In this study, transcriptome profiling of a random insertional mutant with enhanced lipid production generated from a non-model marine microalga Dunaliella tertiolecta is presented. D9 mutant has a lipid yield that is 2- to 4-fold higher than that of wild type. Using novel Bag2D-workflow scripts developed and reported here, the non-redundant transcripts from de novo assembly were annotated based on the best hits in five model microalgae, namely Chlamydomonas reinhardtii, Coccomyxa subellipsoidea C-169, Ostreococcus lucimarinus, Volvox carteri, Chlorella variabilis NC64A and a high plant species Arabidopsis thaliana. The assembled contigs (~181 Mb) includes 481,381 contigs, covering 10,185 genes. Pathway analysis showed that a pathway from inositol phosphate metabolism to fatty acid biosynthesis is the most significantly correlated with higher lipid yield in this mutant. Herein, we described a pipeline to analyze RNA-Seq data without pre-existing transcriptomic information. The draft transcriptome of D. tertiolecta was constructed and annotated, which offered useful information for characterizing high lipid-producing mutants. D. tertiolecta mutant was generated with an enhanced photosynthetic efficiency and lipid production. RNA-Seq data of the mutant and wild type were compared, providing biological insights into the expression patterns of contigs associated with energy

  19. Methods of Developing User-Friendly Keys to Identify Green Sea Turtles (Chelonia mydas L. from Photographs

    Directory of Open Access Journals (Sweden)

    Jane R. Lloyd

    2012-01-01

    Full Text Available Identifying individual animals is important in understanding their ecology and behaviour, as well as providing estimates of population sizes for conservation efforts. We produce identification keys from photographs of green sea turtles to identify them while foraging in Akumal Bay, Mexico. We create three keys, which (a minimise the length of the key, (b present the most obvious differential characteristics first, and (c remove the strict dichotomy from key b. Keys were capable of identifying >99% of turtles in >2500 photographs during the six-month study period. The keys differed significantly in success rate for students to identify individual turtles, with key (c being the best with >70% success and correctly being followed further than other keys before making a mistake. User-friendly keys are, therefore, a suitable method for the photographic identification of turtles and could be used for other large marine vertebrates in conservation or behavioural studies.

  20. On linear models and parameter identifiability in experimental biological systems.

    Science.gov (United States)

    Lamberton, Timothy O; Condon, Nicholas D; Stow, Jennifer L; Hamilton, Nicholas A

    2014-10-07

    A key problem in the biological sciences is to be able to reliably estimate model parameters from experimental data. This is the well-known problem of parameter identifiability. Here, methods are developed for biologists and other modelers to design optimal experiments to ensure parameter identifiability at a structural level. The main results of the paper are to provide a general methodology for extracting parameters of linear models from an experimentally measured scalar function - the transfer function - and a framework for the identifiability analysis of complex model structures using linked models. Linked models are composed by letting the output of one model become the input to another model which is then experimentally measured. The linked model framework is shown to be applicable to designing experiments to identify the measured sub-model and recover the input from the unmeasured sub-model, even in cases that the unmeasured sub-model is not identifiable. Applications for a set of common model features are demonstrated, and the results combined in an example application to a real-world experimental system. These applications emphasize the insight into answering "where to measure" and "which experimental scheme" questions provided by both the parameter extraction methodology and the linked model framework. The aim is to demonstrate the tools' usefulness in guiding experimental design to maximize parameter information obtained, based on the model structure.

  1. Global identifiability of linear structural equation models

    CERN Document Server

    Drton, Mathias; Sullivant, Seth

    2010-01-01

    Structural equation models are multivariate statistical models that are defined by specifying noisy functional relationships among random variables. We consider the classical case of linear relationships and additive Gaussian noise terms. We give a necessary and sufficient condition for global identifiability of the model in terms of a mixed graph encoding the linear structural equations and the correlation structure of the error terms. Global identifiability is understood to mean injectivity of the parametrization of the model and is fundamental in particular for applicability of standard statistical methodology.

  2. Identifying and weighting of key performance indicators of knowledge management2.0 in organizations

    Directory of Open Access Journals (Sweden)

    Saeed Khalilazar

    2016-03-01

    Full Text Available Main purpose of this research is identifying and weighting of key performance indicators of knowledge management2.0 in organizations. According to widespread permeation of technology, especially social media in different organizational dimensions and functional view to this phenomenon in knowledge management, performance measurement of this kind of media in order to meet organizational goals seems necessary. KM2.0 key performance indicators in this article has been identified and weighted through Delphi methodology, via questionnaire in three rounds. KM2.0 KPIs which are identified and weighted in this article are applicable in organizations that are eager to implement KM2.0 initiative and they can measure the performance of KM2.0 activities therefore this research is applicable in goal oriented approach. According to the results, KM2.0 participation process consists of 3 stages and 8 steps as mentioned below: First stage which is presence, consists of 3 steps which are registration, visit and download. Second stage which is feedback consists of 3 steps which are conversation, applause and amplification. Finally, third stage which is creation consists of 2 steps which are codification and personalization. Ultimate contribution of this research is identifying and weighting KPIs of KM2.0 in conceptual framework of KM2.0. Based on developing a conceptual framework and participation process in KM2.0 and listing related KPIs as an applicable solution in order to measure and improve the performance of organizational social media, this research has unique innovation among related and other articles.

  3. The Probabilistic Model of Keys Generation of QKD Systems

    CERN Document Server

    Golubchikov, Dmitry

    2010-01-01

    The probabilistic model of keys generation of QKD systems is proposed. The model includes all phases of keys generation starting from photons generation to states detection taking characteristics of fiber-optics components into account. The paper describes the tree of events of QKD systems. Equations are found for estimation of the effectiveness of the process of sifted keys generation as well as for bit-error probability and for the rate of private keys generation.

  4. GuiaTreeKey, a multi-access electronic key to identify tree genera in French Guiana

    Science.gov (United States)

    Engel, Julien; Brousseau, Louise; Baraloto, Christopher

    2016-01-01

    Abstract The tropical rainforest of Amazonia is one of the most species-rich ecosystems on earth, with an estimated 16000 tree species. Due to this high diversity, botanical identification of trees in the Amazon is difficult, even to genus, often requiring the assistance of parataxonomists or taxonomic specialists. Advances in informatics tools offer a promising opportunity to develop user-friendly electronic keys to improve Amazonian tree identification. Here, we introduce an original multi-access electronic key for the identification of 389 tree genera occurring in French Guiana terra-firme forests, based on a set of 79 morphological characters related to vegetative, floral and fruit characters. Its purpose is to help Amazonian tree identification and to support the dissemination of botanical knowledge to non-specialists, including forest workers, students and researchers from other scientific disciplines. The electronic key is accessible with the free access software Xper², and the database is publicly available on figshare: https://figshare.com/s/75d890b7d707e0ffc9bf (doi: 10.6084/m9.figshare.2682550). PMID:27698572

  5. Framework for Identifying Key Environmental Concerns in Marine Renewable Energy Projects- Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, Sharon; Previsic, Mirko; Nelson, Peter; Woo, Sheri

    2010-06-17

    Marine wave and tidal energy technology could interact with marine resources in ways that are not well understood. As wave and tidal energy conversion projects are planned, tested, and deployed, a wide range of stakeholders will be engaged; these include developers, state and federal regulatory agencies, environmental groups, tribal governments, recreational and commercial fishermen, and local communities. Identifying stakeholders’ environmental concerns in the early stages of the industry’s development will help developers address and minimize potential environmental effects. Identifying important concerns will also assist with streamlining siting and associated permitting processes, which are considered key hurdles by the industry in the U.S. today. In September 2008, RE Vision consulting, LLC was selected by the Department of Energy (DoE) to conduct a scenario-based evaluation of emerging hydrokinetic technologies. The purpose of this evaluation is to identify and characterize environmental impacts that are likely to occur, demonstrate a process for analyzing these impacts, identify the “key” environmental concerns for each scenario, identify areas of uncertainty, and describe studies that could address that uncertainty. This process is intended to provide an objective and transparent tool to assist in decision-making for siting and selection of technology for wave and tidal energy development. RE Vision worked with H. T. Harvey & Associates, to develop a framework for identifying key environmental concerns with marine renewable technology. This report describes the results of this study. This framework was applied to varying wave and tidal power conversion technologies, scales, and locations. The following wave and tidal energy scenarios were considered: 4 wave energy generation technologies 3 tidal energy generation technologies 3 sites: Humboldt coast, California (wave); Makapu’u Point, Oahu, Hawaii (wave); and the Tacoma Narrows, Washington (tidal

  6. Key West, Florida Tsunami Forecast Grids for MOST Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Key West, Florida Forecast Model Grids provides bathymetric data strictly for tsunami inundation modeling with the Method of Splitting Tsunami (MOST) model. MOST...

  7. Key West, Florida Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Discrete Event Simulation Modeling and Analysis of Key Leader Engagements

    Science.gov (United States)

    2012-06-01

    SIMULATION MODELING AND ANALYSIS OF KEY LEADER ENGAGEMENTS by Clifford C. Wakeman June 2012 Thesis Co-Advisors: Arnold H. Buss Susan...DATE June 2012 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE Discrete Event Simulation Modeling and Analysis of Key...for public release; distribution is unlimited DISCRETE EVENT SIMULATION MODELING AND ANALYSIS OF KEY LEADER ENGAGEMENTS Clifford C. Wakeman

  9. Orthognathic model surgery with LEGO key-spacer.

    Science.gov (United States)

    Tsang, Alfred Chee-Ching; Lee, Alfred Siu Hong; Li, Wai Keung

    2013-12-01

    A new technique of model surgery using LEGO plates as key-spacers is described. This technique requires less time to set up compared with the conventional plaster model method. It also retains the preoperative setup with the same set of models. Movement of the segments can be measured and examined in detail with LEGO key-spacers.

  10. [Key effect genes responding to nerve injury identified by gene ontology and computer pattern recognition].

    Science.gov (United States)

    Pan, Qian; Peng, Jin; Zhou, Xue; Yang, Hao; Zhang, Wei

    2012-07-01

    In order to screen out important genes from large gene data of gene microarray after nerve injury, we combine gene ontology (GO) method and computer pattern recognition technology to find key genes responding to nerve injury, and then verify one of these screened-out genes. Data mining and gene ontology analysis of gene chip data GSE26350 was carried out through MATLAB software. Cd44 was selected from screened-out key gene molecular spectrum by comparing genes' different GO terms and positions on score map of principal component. Function interferences were employed to influence the normal binding of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite extension. Gene ontology analysis showed that the first genes on score map (marked by red *) mainly distributed in molecular transducer activity, receptor activity, protein binding et al molecular function GO terms. Cd44 is one of six effector protein genes, and attracted us with its function diversity. After adding different reagents into the medium to interfere the normal binding of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite extension were observed. CSC can inhibit neurite extension through binding Cd44 on the neuron membrane. This verifies that important genes in given physiological processes can be identified by gene ontology analysis of gene chip data.

  11. A systems biological approach to identify key transcription factors and their genomic neighborhoods in human sarcomas

    Institute of Scientific and Technical Information of China (English)

    Antti Ylip(a)(a); Olli Yli-Harja; Wei Zhang; Matti Nykter

    2011-01-01

    Identification of genetic signatures is the main objective for many computational oncology studies. The signature usually consists of numerous genes that are differentially expressed between two clinically distinct groups of samples, such as tumor subtypes. Prospectively, many signatures have been found to generalize poorly to other datasets and, thus, have rarely been accepted into clinical use. Recognizing the limited success of traditionally generated signatures, we developed a systems biology-based framework for robust identification of key transcription factors and their genomic regulatory neighborhoods. Application of the framework to study the differences between gastrointestinal stromal tumor (GIST) and leiomyosarcoma (LMS) resulted in the identification of nine transcription factors (SRF, NKX2-5, CCDC6, LEF1, VDR, ZNF250, TRIM63, MAF, and MYC). Functional annotations of the obtained neighborhoods identified the biological processes which the key transcription factors regulate differently between the tumor types. Analyzing the differences in the expression patterns using our approach resulted in a more robust genetic signature and more biological insight into the diseases compared to a traditional genetic signature.

  12. Identifying Regional Key Eco-Space to Maintain Ecological Security Using GIS

    Science.gov (United States)

    Xie, Hualin; Yao, Guanrong; Wang, Peng

    2014-01-01

    Ecological security and environmental sustainability are the foundations of sustainable development. With the acceleration of urbanization, increasing human activities have promoted greater impacts on the eco-spaces that maintain ecological security. Regional key eco-space has become the primary need to maintain environmental sustainability and can offer society with continued ecosystem services. In this paper, considering the security of water resources, biodiversity conservation, disaster avoidance and protection and natural recreation, an integrated index of eco-space importance was established and a method for identifying key eco-space was created using GIS, with Lanzhou City, China as a case study. The results show that the area of core eco-space in the Lanzhou City is approximately 50,908.7 hm2, accounting for 40% of the region’s total area. These areas mainly consist of geological hazard protection zones and the core zones of regional river systems, wetlands, nature reserves, forest parks and scenic spots. The results of this study provide some guidance for the management of ecological security, ecological restoration and environmental sustainability. PMID:24590051

  13. Identifying Regional Key Eco-Space to Maintain Ecological Security Using GIS

    Directory of Open Access Journals (Sweden)

    Hualin Xie

    2014-02-01

    Full Text Available Ecological security and environmental sustainability are the foundations of sustainable development. With the acceleration of urbanization, increasing human activities have promoted greater impacts on the eco-spaces that maintain ecological security. Regional key eco-space has become the primary need to maintain environmental sustainability and can offer society with continued ecosystem services. In this paper, considering the security of water resources, biodiversity conservation, disaster avoidance and protection and natural recreation, an integrated index of eco-space importance was established and a method for identifying key eco-space was created using GIS, with Lanzhou City, China as a case study. The results show that the area of core eco-space in the Lanzhou City is approximately 50,908.7 hm2, accounting for 40% of the region’s total area. These areas mainly consist of geological hazard protection zones and the core zones of regional river systems, wetlands, nature reserves, forest parks and scenic spots. The results of this study provide some guidance for the management of ecological security, ecological restoration and environmental sustainability.

  14. Identifying regional key eco-space to maintain ecological security using GIS.

    Science.gov (United States)

    Xie, Hualin; Yao, Guanrong; Wang, Peng

    2014-02-28

    Ecological security and environmental sustainability are the foundations of sustainable development. With the acceleration of urbanization, increasing human activities have promoted greater impacts on the eco-spaces that maintain ecological security. Regional key eco-space has become the primary need to maintain environmental sustainability and can offer society with continued ecosystem services. In this paper, considering the security of water resources, biodiversity conservation, disaster avoidance and protection and natural recreation, an integrated index of eco-space importance was established and a method for identifying key eco-space was created using GIS, with Lanzhou City, China as a case study. The results show that the area of core eco-space in the Lanzhou City is approximately 50,908.7 hm(2), accounting for 40% of the region's total area. These areas mainly consist of geological hazard protection zones and the core zones of regional river systems, wetlands, nature reserves, forest parks and scenic spots. The results of this study provide some guidance for the management of ecological security, ecological restoration and environmental sustainability.

  15. Identifying IDS Agent Nodes Based on 3-Layered Key Management Framework for MANET

    Directory of Open Access Journals (Sweden)

    Marjan KUCHAKI RAFSANJANI

    2014-02-01

    Full Text Available Nowadays, Mobile Ad Hoc Networks (MANETs have become one of the most important networks in advanced technologies. However, MANETs are more vulnerable than wired and wireless networks to active and passive attacks. So, security and intrusion detection are very important in these networks. In this paper, we have presented a method of identifying IDS agent nodes in MANET. Whereas, IDS agent nodes due to monitoring activities in Intrusion Detection Systems (IDSs need more battery energy than other nodes in the network. In the first step, our method uses a 3-layered key management framework in order to authenticate and then in the second step, nodes with higher battery power from among authorized nodes as IDS agent nodes are considered. Therefore, with this method, some authorized nodes contribute in monitoring activities and the network lifetime will be increased and also communication cost in the 3-layered key management framework is less than other frameworks, thus communication performance will be increased.doi:10.14456/WJST.2014.30

  16. Identifying nonlinear biomechanical models by multicriteria analysis

    Science.gov (United States)

    Srdjevic, Zorica; Cveticanin, Livija

    2012-02-01

    In this study, the methodology developed by Srdjevic and Cveticanin (International Journal of Industrial Ergonomics 34 (2004) 307-318) for the nonbiased (objective) parameter identification of the linear biomechanical model exposed to vertical vibrations is extended to the identification of n-degree of freedom (DOF) nonlinear biomechanical models. The dynamic performance of the n-DOF nonlinear model is described in terms of response functions in the frequency domain, such as the driving-point mechanical impedance and seat-to-head transmissibility function. For randomly generated parameters of the model, nonlinear equations of motion are solved using the Runge-Kutta method. The appropriate data transformation from the time-to-frequency domain is performed by a discrete Fourier transformation. Squared deviations of the response functions from the target values are used as the model performance evaluation criteria, thus shifting the problem into the multicriteria framework. The objective weights of criteria are obtained by applying the Shannon entropy concept. The suggested methodology is programmed in Pascal and tested on a 4-DOF nonlinear lumped parameter biomechanical model. The identification process over the 2000 generated sets of parameters lasts less than 20 s. The model response obtained with the imbedded identified parameters correlates well with the target values, therefore, justifying the use of the underlying concept and the mathematical instruments and numerical tools applied. It should be noted that the identified nonlinear model has an improved accuracy of the biomechanical response compared to the accuracy of a linear model.

  17. Identifying key areas for active interprofessional learning partnerships: A facilitated dialogue.

    Science.gov (United States)

    Steven, Kathryn; Angus, Allyson; Breckenridge, Jenna; Davey, Peter; Tully, Vicki; Muir, Fiona

    2016-11-01

    Student and service user involvement is recognised as an important factor in creating interprofessional education (IPE) opportunities. We used a team-based learning approach to bring together undergraduate health professional students, early career professionals (ECPs), public partners, volunteers, and carers to explore learning partnerships. Influenced by evaluative inquiry, this qualitative study used a free text response to allow participants to give their own opinion. A total of 153 participants (50 public partners and 103 students and professionals representing 11 healthcare professions) took part. Participants were divided into mixed groups of six (n = 25) and asked to identify areas where students, professionals, and public could work together to improve health professional education. Each group documented their discussions by summarising agreed areas and next steps. Responses were collected and transcribed for inductive content analysis. Seven key themes (areas for joint working) were identified: communication, public as partners, standards of conduct, IPE, quality improvement, education, and learning environments. The team-based learning format enabled undergraduate and postgraduate health professionals to achieve consensus with public partners on areas for IPE and collaboration. Some of our results may be context-specific but the approach is generalisable to other areas.

  18. Identifying key parameters to differentiate groundwater flow systems using multifactorial analysis

    Science.gov (United States)

    Menció, Anna; Folch, Albert; Mas-Pla, Josep

    2012-11-01

    SummaryMultivariate techniques are useful in hydrogeological studies to reduce the complexity of large-scale data sets, and provide more understandable insight into the system hydrology. In this study, principal component analysis (PCA) has been used as an exploratory method to identify the key parameters that define distinct flow systems in the Selva basin (NE Spain). In this statistical analysis, all the information obtained in hydrogeological studies (that is, hydrochemical and isotopic data, but also potentiometric data) is used. Additionally, cluster analysis, based on PCA results, allows the associations between samples to be identified, and thus, corroborates the occurrence of different groundwater fluxes. PCA and cluster analysis reveal that two main groundwater flow systems exist in the Selva basin, each with distinct hydrochemical, isotopic, and potentiometric features. Regional groundwater fluxes are associated with high F- contents, and confined aquifer layers; while local fluxes are linked to nitrate polluted unconfined aquifers with a different recharge rates. In agreement with previous hydrogeological studies, these statistical methods stand as valid screening tools to highlight the fingerprint variables that can be used as indicators to facilitate further, more arduous, analytical approaches and a feasible interpretation of the whole data set.

  19. Identifiability of large phylogenetic mixture models.

    Science.gov (United States)

    Rhodes, John A; Sullivant, Seth

    2012-01-01

    Phylogenetic mixture models are statistical models of character evolution allowing for heterogeneity. Each of the classes in some unknown partition of the characters may evolve by different processes, or even along different trees. Such models are of increasing interest for data analysis, as they can capture the variety of evolutionary processes that may be occurring across long sequences of DNA or proteins. The fundamental question of whether parameters of such a model are identifiable is difficult to address, due to the complexity of the parameterization. Identifiability is, however, essential to their use for statistical inference.We analyze mixture models on large trees, with many mixture components, showing that both numerical and tree parameters are indeed identifiable in these models when all trees are the same. This provides a theoretical justification for some current empirical studies, and indicates that extensions to even more mixture components should be theoretically well behaved. We also extend our results to certain mixtures on different trees, using the same algebraic techniques.

  20. Identifying motifs in folktales using topic models

    NARCIS (Netherlands)

    Karsdorp, F.; Bosch, A.P.J. van den

    2013-01-01

    With the undertake of various folktale digitalization initiatives, the need for computational aids to explore these collections is increasing. In this paper we compare Labeled LDA (L-LDA) to a simple retrieval model on the task of identifying motifs in folktales. We show that both methods are well a

  1. Identifiability of Causal Graphs using Functional Models

    CERN Document Server

    Peters, Jonas; Janzing, Dominik; Schoelkopf, Bernhard

    2012-01-01

    This work addresses the following question: Under what assumptions on the data generating process can one infer the causal graph from the joint distribution? The approach taken by conditional independence-based causal discovery methods is based on two assumptions: the Markov condition and faithfulness. It has been shown that under these assumptions the causal graph can be identified up to Markov equivalence (some arrows remain undirected) using methods like the PC algorithm. In this work we propose an alternative by defining Identifiable Functional Model Classes (IFMOCs). As our main theorem we prove that if the data generating process belongs to an IFMOC, one can identify the complete causal graph. To the best of our knowledge this is the first identifiability result of this kind that is not limited to linear functional relationships. We discuss how the IFMOC assumption and the Markov and faithfulness assumptions relate to each other and explain why we believe that the IFMOC assumption can be tested more eas...

  2. Framework for Identifying Key Environmental Concerns in Marine Renewable Energy Projects- Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, Sharon; Previsic, Mirko; Nelson, Peter; Woo, Sheri

    2010-06-17

    Marine wave and tidal energy technology could interact with marine resources in ways that are not well understood. As wave and tidal energy conversion projects are planned, tested, and deployed, a wide range of stakeholders will be engaged; these include developers, state and federal regulatory agencies, environmental groups, tribal governments, recreational and commercial fishermen, and local communities. Identifying stakeholders’ environmental concerns in the early stages of the industry’s development will help developers address and minimize potential environmental effects. Identifying important concerns will also assist with streamlining siting and associated permitting processes, which are considered key hurdles by the industry in the U.S. today. In September 2008, RE Vision consulting, LLC was selected by the Department of Energy (DoE) to conduct a scenario-based evaluation of emerging hydrokinetic technologies. The purpose of this evaluation is to identify and characterize environmental impacts that are likely to occur, demonstrate a process for analyzing these impacts, identify the “key” environmental concerns for each scenario, identify areas of uncertainty, and describe studies that could address that uncertainty. This process is intended to provide an objective and transparent tool to assist in decision-making for siting and selection of technology for wave and tidal energy development. RE Vision worked with H. T. Harvey & Associates, to develop a framework for identifying key environmental concerns with marine renewable technology. This report describes the results of this study. This framework was applied to varying wave and tidal power conversion technologies, scales, and locations. The following wave and tidal energy scenarios were considered: 4 wave energy generation technologies 3 tidal energy generation technologies 3 sites: Humboldt coast, California (wave); Makapu’u Point, Oahu, Hawaii (wave); and the Tacoma Narrows, Washington (tidal

  3. Transcriptome Analysis Identifies Key Candidate Genes Mediating Purple Ovary Coloration in Asiatic Hybrid Lilies

    Science.gov (United States)

    Xu, Leifeng; Yang, Panpan; Yuan, Suxia; Feng, Yayan; Xu, Hua; Cao, Yuwei; Ming, Jun

    2016-01-01

    Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value of the flower is lost. Some cultivars have attractive purple ovaries and fruits which greatly enhance the ornamental value of Asiatic hybrid lilies. However, little is known about the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. To investigate the transcriptional network that governs purple ovary coloration in Asiatic hybrid lilies, we obtained transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic “Tiny Padhye”. Comparative transcriptome analysis revealed 4228 differentially expressed genes. Differential expression analysis revealed that ten unigenes including four CHS genes, one CHI gene, one F3H gene, one F3′H gene, one DFR gene, one UFGT gene, and one 3RT gene were significantly up-regulated in purple ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor determining the distribution of anthocyanins in Asiatic hybrid lily ovaries. Further qPCR results showed unigenes related to anthocyanin biosynthesis were highly expressed in purple ovaries of three purple-ovaried Asiatic hybrid lilies at stages 2 and 3, while they showed an extremely low level of expression in ovaries of three green-ovaried Asiatic hybrid lilies during all developmental stages. In addition, shading treatment significantly decreased pigment accumulation by suppressing the expression of several unigenes related to anthocyanin biosynthesis in ovaries of Asiatic “Tiny Padhye”. Lastly, a total of 15,048 Simple Sequence Repeats (SSRs) were identified in 13,710 sequences, and primer pairs for SSRs were designed. The results could further our understanding of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. PMID:27879624

  4. Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche.

    Directory of Open Access Journals (Sweden)

    Yao-Zhong Liu

    2009-03-01

    Full Text Available For females, menarche is a most significant physiological event. Age at menarche (AAM is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects--all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan, which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR q<0.05. Six most significant SNPs of the gene were selected for validation in three independent replication cohorts. All of the six SNPs were replicated in at least one cohort. In particular, SNPs rs13357391 and rs1859345 were replicated both within and across different ethnic groups in all three cohorts, with p values of 5.09 x 10(-3 and 4.37 x 10(-3, respectively, in the Chinese cohort and combined p values (obtained by Fisher's method of 5.19 x 10(-5 and 1.02 x 10(-4, respectively, in all three replication cohorts. Interestingly, SPOCK can inhibit activation of MMP-2 (matrix metalloproteinase-2, a key factor promoting endometrial menstrual breakdown and onset of menstrual bleeding. Our findings, together with the functional relevance, strongly supported that the SPOCK gene underlies variation of AAM.

  5. The CD10 enzyme is a key player to identify and regulate human mammary stem cells.

    Science.gov (United States)

    Bachelard-Cascales, Elodie; Chapellier, Marion; Delay, Emmanuel; Pochon, Gaetan; Voeltzel, Thibault; Puisieux, Alain; Caron de Fromentel, Claude; Maguer-Satta, Véronique

    2010-06-01

    The major components of the mammary ductal tree are an inner layer of luminal cells, an outer layer of myoepithelial cells, and a basement membrane that separates the ducts from the underlying stroma. Cells in the outer layer express CD10, a zinc-dependent metalloprotease that regulates the growth of the ductal tree during mammary gland development. To define the steps in the human mammary lineage at which CD10 acts, we have developed an in vitro assay for human mammary lineage progression. We show that sorting for CD10 and EpCAM cleanly separates progenitors from differentiated luminal cells and that the CD10-high EpCAM-low population is enriched for early common progenitor and mammosphere-forming cells. We also show that sorting for CD10 enriches sphere-forming cells from other tissue types, suggesting that it may provide a simple tool to identify stem or progenitor populations in tissues for which lineage studies are not currently possible. We demonstrate that the protease activity of CD10 and the adhesion function of beta1-integrin are required to prevent differentiation of mammary progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signaling factors by CD10 are key elements in the niche that maintains the progenitor and stem cell pools in the mammary lineage.

  6. Identifying confounders using additive noise models

    CERN Document Server

    Janzing, Dominik; Mooij, Joris; Schoelkopf, Bernhard

    2012-01-01

    We propose a method for inferring the existence of a latent common cause ('confounder') of two observed random variables. The method assumes that the two effects of the confounder are (possibly nonlinear) functions of the confounder plus independent, additive noise. We discuss under which conditions the model is identifiable (up to an arbitrary reparameterization of the confounder) from the joint distribution of the effects. We state and prove a theoretical result that provides evidence for the conjecture that the model is generically identifiable under suitable technical conditions. In addition, we propose a practical method to estimate the confounder from a finite i.i.d. sample of the effects and illustrate that the method works well on both simulated and real-world data.

  7. Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation.

    Science.gov (United States)

    Servetas, Stephanie L; Carpenter, Beth M; Haley, Kathryn P; Gilbreath, Jeremy J; Gaddy, Jennifer A; Merrell, D Scott

    2016-09-15

    Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, ΔnikR ΔarsS, and Δfur ΔnikR ΔarsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. Despite a paucity of regulatory proteins, adaptation is key to the survival of H. pylori within the stomach. While prior studies have focused on individual regulatory proteins

  8. Dynamic height: A key variable for identifying the spawning habitat of small pelagic fishes

    Science.gov (United States)

    Asch, Rebecca G.; Checkley, David M., Jr.

    2013-01-01

    Small pelagic fishes off southern California exhibit interannual variations in the regions they occupy. An enhanced understanding of these fluctuations could improve fisheries management and predictions of fish's responses to climate change. We investigated dynamic height as a variable for identifying the spawning habitat of northern anchovy (Engraulis mordax), Pacific sardine (Sardinops sagax), and jack mackerel (Trachurus symmetricus). During cruises between 1998 and 2004, dynamic height was calculated from temperature and salinity profiles, while fish egg concentration was measured with obliquely towed bongo nets and the Continuous, Underway Fish Egg Sampler. Dynamic height ranged between 68 and 108 cm, with values increasing offshore. The greatest probability of encountering anchovy, sardine, and jack mackerel eggs occurred at dynamic heights of 79-83 cm, 84-89 cm, and 89-99 cm, respectively. Four mechanisms were proposed to explain how dynamic height affects egg distribution: (1) dynamic height is a proxy for upper water column temperature and salinity, which are known to influence spawning habitat. (2) Low dynamic heights are indicative of coastal upwelling, which increases primary and secondary productivity. (3) Egg concentration is greater at dynamic heights coincident with geostrophic currents that transport larvae to favorable habitats. (4) Eddies delineated by dynamic height contours retain eggs in productive habitats. To evaluate these mechanisms, a generalized linear model was constructed using dynamic height, temperature, salinity, chlorophyll, zooplankton volume, geostrophic currents, and eddies as independent variables. Dynamic height explained more variance than any other variable in models of sardine and anchovy spawning habitat. Together temperature, salinity, and chlorophyll accounted for 80-95% of the dynamic height effect, emphasizing the importance of the first two mechanisms. However, dynamic height remained statistically significant in the

  9. Key characters for identifying Aedes bahamensis and Aedes albopictus in North America, north of Mexico.

    Science.gov (United States)

    Darsie, R F

    1992-09-01

    Aedes bahamensis, a species recently introduced into southern Florida represents the first member of the subgenus Howardina to be found in the United States. Its separation from all other Nearctic Aedes is the subject of this work, integrating it into the North American mosquito keys (Darsie and Ward 1981). The key revisions presented are expanded to include the other exotic species now found in the United States, Aedes albopictus.

  10. Key performance indicators in hospital based on balanced scorecard model

    Directory of Open Access Journals (Sweden)

    Hamed Rahimi

    2017-01-01

    Full Text Available Introduction: Performance measurement is receiving increasing verification all over the world. Nowadays in a lot of organizations, irrespective of their type or size, performance evaluation is the main concern and a key issue for top administrators. The purpose of this study is to organize suitable key performance indicators (KPIs for hospitals’ performance evaluation based on the balanced scorecard (BSC. Method: This is a mixed method study. In order to identify the hospital’s performance indicators (HPI, first related literature was reviewed and then the experts’ panel and Delphi method were used. In this study, two rounds were needed for the desired level of consensus. The experts rated the importance of the indicators, on a five-point Likert scale. In the consensus calculation, the consensus percentage was calculated by classifying the values 1-3 as not important (0 and 4-5 to (1 as important. Simple additive weighting technique was used to rank the indicators and select hospital’s KPIs. The data were analyzed by Excel 2010 software. Results: About 218 indicators were obtained from a review of selected literature. Through internal expert panel, 77 indicators were selected. Finally, 22 were selected for KPIs of hospitals. Ten indicators were selected in internal process perspective and 5, 4, and 3 indicators in finance, learning and growth, and customer, respectively. Conclusion: This model can be a useful tool for evaluating and comparing the performance of hospitals. However, this model is flexible and can be adjusted according to differences in the target hospitals. This study can be beneficial for hospital administrators and it can help them to change their perspective about performance evaluation.

  11. An evidence-based knowledgebase of metastasis suppressors to identify key pathways relevant to cancer metastasis.

    Science.gov (United States)

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-10-21

    Metastasis suppressor genes (MS genes) are genes that play important roles in inhibiting the process of cancer metastasis without preventing growth of the primary tumor. Identification of these genes and understanding their functions are critical for investigation of cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility MS genes. However, the comprehensive illustration of diverse cellular processes regulated by metastasis suppressors during the metastasis cascade is lacking. Thus, the relationship between MS genes and cancer risk is still unclear. To unveil the cellular complexity of MS genes, we have constructed MSGene (http://MSGene.bioinfo-minzhao.org/), the first literature-based gene resource for exploring human MS genes. In total, we manually curated 194 experimentally verified MS genes and mapped to 1448 homologous genes from 17 model species. Follow-up functional analyses associated 194 human MS genes with epithelium/tissue morphogenesis and epithelia cell proliferation. In addition, pathway analysis highlights the prominent role of MS genes in activation of platelets and coagulation system in tumor metastatic cascade. Moreover, global mutation pattern of MS genes across multiple cancers may reveal common cancer metastasis mechanisms. All these results illustrate the importance of MSGene to our understanding on cell development and cancer metastasis.

  12. A key for identifying faecal smears to detect domestic infestations of triatomine bugs

    Directory of Open Access Journals (Sweden)

    C.J. Schofield

    1986-03-01

    Full Text Available Early detection of residual populations of domestic triatomine bugs that survive insecticide treatment is a key component of successful evaluation and vigilance for Chagas disease control. We have recently demonstrated that sheets of paper, tacked on to the walls of infested houses, can become streaked with the faeces of triatomine bugs and thus reveal thepresence of an infestation. In thispaper, wepresent a simple key to differentiate the faecal streaks of triatomine bugs from those of other domestic arthropods such as cockroaches, ticks and cimicid bedbugs.

  13. Secret Key Generation for a Pairwise Independent Network Model

    CERN Document Server

    Nitinawarat, Sirin; Barg, Alexander; Narayan, Prakash; Reznik, Alex

    2010-01-01

    We consider secret key generation for a "pairwise independent network" model in which every pair of terminals observes correlated sources that are independent of sources observed by all other pairs of terminals. The terminals are then allowed to communicate publicly with all such communication being observed by all the terminals. The objective is to generate a secret key shared by a given subset of terminals at the largest rate possible, with the cooperation of any remaining terminals. Secrecy is required from an eavesdropper that has access to the public interterminal communication. A (single-letter) formula for secret key capacity brings out a natural connection between the problem of secret key generation and a combinatorial problem of maximal packing of Steiner trees in an associated multigraph. An explicit algorithm is proposed for secret key generation based on a maximal packing of Steiner trees in a multigraph; the corresponding maximum rate of Steiner tree packing is thus a lower bound for the secret ...

  14. Identifying Key Topics for the Description of Sexual Behavior in the Danish Population: A Qualitative Study

    DEFF Research Database (Denmark)

    Jørgensen, Marianne Johansson

    abuse and internet dating to be triggers of unsafe sex. Conclusion According to Danish adolescents there were four important key topics which could lead to unsafe sex and these points differed slightly from our expectations. Those points of interest will be included in a sexual behavior questionnaire...

  15. metaModules identifies key functional subnetworks in microbiome-related disease

    NARCIS (Netherlands)

    A. May (Ali); B.W. Brandt (Bernd); M. El-Kebir (Mohammed); G.W. Klau (Gunnar); E. Zaura (Egija); W. Crielaard (Wim); J. Heringa (Jaap); S. Abeln (Sanne)

    2015-01-01

    htmlabstractMotivation: The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods

  16. metaModules identifies key functional subnetworks in microbiome-related disease

    NARCIS (Netherlands)

    May, A.; Brandt, B.W.; El-Kebir, M.; Klau, G.W.; Zaura, E.; Crielaard, W.; Heringa, J.; Abeln, S.

    2016-01-01

    Motivation: The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods provide a systemic

  17. Identifying Key Features of Student Performance in Educational Video Games and Simulations through Cluster Analysis

    Science.gov (United States)

    Kerr, Deirdre; Chung, Gregory K. W. K.

    2012-01-01

    The assessment cycle of "evidence-centered design" (ECD) provides a framework for treating an educational video game or simulation as an assessment. One of the main steps in the assessment cycle of ECD is the identification of the key features of student performance. While this process is relatively simple for multiple choice tests, when…

  18. metaModules identifies key functional subnetworks in microbiome-related disease

    NARCIS (Netherlands)

    May, A.; Brandt, B.W.; El-Kebir, M.; Klau, G.W.; Zaura, E.; Crielaard, W.; Heringa, J.; Abeln, S.

    2015-01-01

    Motivation: The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods pro- vide a systemic

  19. Model of key success factors for Business Intelligence implementation

    Directory of Open Access Journals (Sweden)

    Peter Mesaros

    2016-07-01

    Full Text Available New progressive technologies recorded growth in every area. Information-communication technologies facilitate the exchange of information and it facilitates management of everyday activities in enterprises. Specific modules (such as Business Intelligence facilitate decision-making. Several studies have demonstrated the positive impact of Business Intelligence to decision-making. The first step is to put in place the enterprise. The implementation process is influenced by many factors. This article discusses the issue of key success factors affecting to successful implementation of Business Intelligence. The article describes the key success factors for successful implementation and use of Business Intelligence based on multiple studies. The main objective of this study is to verify the effects and dependence of selected factors and proposes a model of key success factors for successful implementation of Business Intelligence. Key success factors and the proposed model are studied in Slovak enterprises.

  20. The queueing model for quantum key distribution network

    Institute of Scientific and Technical Information of China (English)

    Wen Hao; Han Zheng-Fu; Guo Guang-Can; Hong Pei-Lin

    2009-01-01

    This paper develops a QKD (quantum key distribution)-based queueing model to investigate the data delay on QKD link and network, especially that based on trusted relays. It shows the mean packet delay performance of the QKD system. Furthermore, it proposes a key buffering policy which could effectively improve the delay performance in practice. The results will be helpful for quality of service in practical QKD systems.

  1. Identifiability and identification of a Synthesis Load Model

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A Synthesis Load Model (SLM) including both the power load and the distribution network has been proposed in the references. The identifiability of SLM is analyzed at first, it is concluded that the model parameters are identifiable if one of the resistance, reactance and the ratio of them is known. The conclusion is validated through a simulation example. A strategy for parameter identification of SLM is proposed with the combination of the component based approach and the measurement based approach. During parameter identification, only the key parameters playing very important roles in the dynamics of the load and the system are estimated, while the other parameters playing limited role are set as the default values. The proposed strategy is verified by the field measurements.

  2. Identifying key research objectives to make European forests greener for bats

    Directory of Open Access Journals (Sweden)

    Danilo Russo

    2016-07-01

    Full Text Available Bats are a biodiverse mammal order providing key ecosystem services such as pest suppression, pollination and seed dispersal. Bats are also very sensitive to human actions, and significant declines in many bat populations have been recorded consequently. Many bat species find crucial roosting and foraging opportunities in European forests. Such forests have historically been exploited by humans and are still influenced by harvesting. One of the consequences of this pressure is the loss of key habitat resources, often making forests inhospitable to bats. Despite the legal protection granted to bats across Europe, the impacts of forestry on bats are still often neglected. Because forest exploitation influences forest structure at several spatial scales, economically viable forestry could become more sustainable and even favour bats. We highlight that a positive future for bat conservation that simultaneously benefits forestry is foreseeable, although more applied research is needed to develop sound management. Key future research topics include the detection of factors influencing the carrying capacity of forests, and determining the impacts of forest management and the economic importance of bats in forests. Predictive tools to inform forest managers are much needed, together with greater synergies between forest managers and bat conservationists.

  3. The phenotypic patterns of essential hypertension are the key to identifying "high blood pressure" genes.

    Science.gov (United States)

    Korner, P I

    2010-01-01

    The genes that cause or increase susceptibility to essential hypertension (EH) and related animal models remain unknown. Their identification is unlikely to be realized with current genetic approaches, because of ambiguities in the genotype-phenotype relationships in these polygenic disorders. In turn, the phenotype is not just an aggregate of traits, but needs to be related to specific components of the circulatory control system at different stages of EH. Hence, clues about important genes must come through the phenotype, reversing the order of current approaches. A recent systems analysis has highlighted major differences in circulatory control in the two main syndromes of EH: (1) stress-and-salt-related EH (SSR-EH)--a constrictor hypertension with low blood volume; (2) hypertensive obesity--SSR-EH plus obesity. Each is initiated through sensitization of central synapses linking the cerebral cortex to the hypothalamic defense area. Several mechanisms are probably involved, including cerebellar effects on baroreflexes. The result is a sustained increase in sympathetic neural activity at stimulus levels that have no effect in normal subjects. Subsequent progression of EH is largely through interactions with non-neural mechanisms, including changes in concentration of vascular autacoids (e.g., nitric oxide) and the amplifying effect of structural changes in large resistance vessels. The rising vasoconstriction increases heterogeneity of blood flow, causing rarefaction (decreased microvascular density) and deterioration of vital organs. SSR-EH also increases food intake in response to stress, but only 40% of these individuals develop hypertensive obesity. Their brain ignores the adiposity signals that normally reduce eating. Hyperinsulinemia masks the sympathetic vasoconstriction through its dilator action, raises blood volume, whilst renal nephropathy and other diabetic complications are common. In each syndrome the neural and non-neural determinants of

  4. The changing model of big pharma: impact of key trends.

    Science.gov (United States)

    Gautam, Ajay; Pan, Xiaogang

    2016-03-01

    Recent years have seen exciting breakthroughs in biomedical sciences that are producing truly novel therapeutics for unmet patient needs. However, the pharmaceutical industry is also facing significant barriers in the form of pricing and reimbursement, continued patent expirations and challenging market dynamics. In this article, we have analyzed data from the 1995-2015 period, on key aspects such as revenue distribution, research units, portfolio mix and emerging markets to identify four key trends that help to understand the change in strategic focus, realignment of R&D footprint, the shift from primary care toward specialty drugs and biologics and the growth of emerging markets as major revenue drivers for big pharma.

  5. Identifying key topics for a description of sexual behavior among Danish adolescents: A qualitative study

    DEFF Research Database (Denmark)

    Jørgensen, Marianne Johansson; Maindal, Helle Terkildsen; Olesen, Frede

    Background: Surveying sexual behavior in the general population serves to identify critical points, monitor the effects, and interpret changes in the spread of sexually transmitted infection. Aim: The aim of this qualitative study was to identify points of particular importance to adolescents....... Results: Four major categories of risk behavior were identified: Alcohol consumption is associated with “no condom use”, Nights on the town and meetings in foreign counties or at festivals are associated with one night stands and often lead to unsafe sex, Low self-esteem increases the risk of pushing one......’ sexual behavior in order to initiate and design a behavior surveillance programme in Denmark. Methods: We conducted four semi-structured focus group interviews with a total of 19 sexually experienced adolescents aged 18 to 23. Boys and girls were interviewed separately. Each group contained pupils from...

  6. Identifying Key Performance Indicators for Holistic Hospital Management with a Modified DEMATEL Approach

    National Research Council Canada - National Science Library

    Sheng-Li Si; Xiao-Yue You; Hu-Chen Liu; Jia Huang

    2017-01-01

    ...) for holistic hospital management. First, through integrating evidential reasoning approach and interval 2-tuple linguistic variables, various assessments of performance indicators provided by healthcare experts are modeled...

  7. A multivariate and stochastic approach to identify key variables to rank dairy farms on profitability.

    Science.gov (United States)

    Atzori, A S; Tedeschi, L O; Cannas, A

    2013-05-01

    The economic efficiency of dairy farms is the main goal of farmers. The objective of this work was to use routinely available information at the dairy farm level to develop an index of profitability to rank dairy farms and to assist the decision-making process of farmers to increase the economic efficiency of the entire system. A stochastic modeling approach was used to study the relationships between inputs and profitability (i.e., income over feed cost; IOFC) of dairy cattle farms. The IOFC was calculated as: milk revenue + value of male calves + culling revenue - herd feed costs. Two databases were created. The first one was a development database, which was created from technical and economic variables collected in 135 dairy farms. The second one was a synthetic database (sDB) created from 5,000 synthetic dairy farms using the Monte Carlo technique and based on the characteristics of the development database data. The sDB was used to develop a ranking index as follows: (1) principal component analysis (PCA), excluding IOFC, was used to identify principal components (sPC); and (2) coefficient estimates of a multiple regression of the IOFC on the sPC were obtained. Then, the eigenvectors of the sPC were used to compute the principal component values for the original 135 dairy farms that were used with the multiple regression coefficient estimates to predict IOFC (dRI; ranking index from development database). The dRI was used to rank the original 135 dairy farms. The PCA explained 77.6% of the sDB variability and 4 sPC were selected. The sPC were associated with herd profile, milk quality and payment, poor management, and reproduction based on the significant variables of the sPC. The mean IOFC in the sDB was 0.1377 ± 0.0162 euros per liter of milk (€/L). The dRI explained 81% of the variability of the IOFC calculated for the 135 original farms. When the number of farms below and above 1 standard deviation (SD) of the dRI were calculated, we found that 21

  8. Identifying Key Topics for the Description of Sexual Behavior in the Danish Population: A Qualitative Study

    DEFF Research Database (Denmark)

    Jørgensen, Marianne Johansson

    verbatim and analysed using qualitative description as the research approach. Results We identified four major categories of risk behavior: 1) Alcohol consumption being associated with no condom use. 2) Nights on the town and meetings in foreign counties or at festivals are associated with one night stands...... other countries, but cultural differences may raise additional or other questions in order to describe the important issues sufficiently. To design and initiate a sexual behavior surveillance program in Denmark, the aim of this qualitative study was therefore to identify focus points of special...

  9. Modeling, Simulation and Analysis of Public Key Infrastructure

    Science.gov (United States)

    Liu, Yuan-Kwei; Tuey, Richard; Ma, Paul (Technical Monitor)

    1998-01-01

    Security is an essential part of network communication. The advances in cryptography have provided solutions to many of the network security requirements. Public Key Infrastructure (PKI) is the foundation of the cryptography applications. The main objective of this research is to design a model to simulate a reliable, scalable, manageable, and high-performance public key infrastructure. We build a model to simulate the NASA public key infrastructure by using SimProcess and MatLab Software. The simulation is from top level all the way down to the computation needed for encryption, decryption, digital signature, and secure web server. The application of secure web server could be utilized in wireless communications. The results of the simulation are analyzed and confirmed by using queueing theory.

  10. Identifying key topics for a description of sexual behavior among Danish adolescents: A qualitative study

    DEFF Research Database (Denmark)

    Jørgensen, Marianne Johansson; Maindal, Helle Terkildsen; Olesen, Frede

    . Results: Four major categories of risk behavior were identified: Alcohol consumption is associated with “no condom use”, Nights on the town and meetings in foreign counties or at festivals are associated with one night stands and often lead to unsafe sex, Low self-esteem increases the risk of pushing one...

  11. Identifying key performance indicators in food technology contract R&D

    NARCIS (Netherlands)

    Flipse, S.M.; Sanden, van der M.C.A.; Velden, van der T.; Fortuin, F.T.J.M.; Omta, S.W.F.; Osseweijer, P.

    2013-01-01

    Innovating companies increasingly rely on outsourcing to Contract Research Organisations (CROs) for their Research and Development (R&D), which are largely understudied. This paper presents the outcome of a case study in the field of food technology contract research, identifying context specifi

  12. Identifying key performance indicators in food technology contract R&D

    NARCIS (Netherlands)

    Flipse, S.M.; Sanden, van der M.C.A.; Velden, van der T.; Fortuin, F.T.J.M.; Omta, S.W.F.; Osseweijer, P.

    2013-01-01

    Innovating companies increasingly rely on outsourcing to Contract Research Organisations (CROs) for their Research and Development (R&D), which are largely understudied. This paper presents the outcome of a case study in the field of food technology contract research, identifying context

  13. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    Science.gov (United States)

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  14. Research on Digital Product Modeling Key Technologies of Digital Manufacturing

    Institute of Scientific and Technical Information of China (English)

    DING Guoping; ZHOU Zude; HU Yefa; ZHAO Liang

    2006-01-01

    With the globalization and diversification of the market and the rapid development of Information Technology (IT) and Artificial Intelligence (AI), the digital revolution of manufacturing is coming. One of the key technologies in digital manufacturing is product digital modeling. This paper firstly analyzes the information and features of the product digital model during each stage in the product whole lifecycle, then researches on the three critical technologies of digital modeling in digital manufacturing-product modeling, standard for the exchange of product model data and digital product data management. And the potential signification of the product digital model during the process of digital manufacturing is concluded-product digital model integrates primary features of each stage during the product whole lifecycle based on graphic features, applies STEP as data exchange mechanism, and establishes PDM system to manage the large amount, complicated and dynamic product data to implement the product digital model data exchange, sharing and integration.

  15. Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Liyan Jiang

    2016-04-01

    Full Text Available Small cell lung cancer (SCLC is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62% harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1 DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

  16. A Systems Approach Identifies Essential FOXO3 Functions at Key Steps of Terminal Erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Raymond Liang

    2015-10-01

    Full Text Available Circulating red blood cells (RBCs are essential for tissue oxygenation and homeostasis. Defective terminal erythropoiesis contributes to decreased generation of RBCs in many disorders. Specifically, ineffective nuclear expulsion (enucleation during terminal maturation is an obstacle to therapeutic RBC production in vitro. To obtain mechanistic insights into terminal erythropoiesis we focused on FOXO3, a transcription factor implicated in erythroid disorders. Using an integrated computational and experimental systems biology approach, we show that FOXO3 is essential for the correct temporal gene expression during terminal erythropoiesis. We demonstrate that the FOXO3-dependent genetic network has critical physiological functions at key steps of terminal erythropoiesis including enucleation and mitochondrial clearance processes. FOXO3 loss deregulated transcription of genes implicated in cell polarity, nucleosome assembly and DNA packaging-related processes and compromised erythroid enucleation. Using high-resolution confocal microscopy and imaging flow cytometry we show that cell polarization is impaired leading to multilobulated Foxo3-/- erythroblasts defective in nuclear expulsion. Ectopic FOXO3 expression rescued Foxo3-/- erythroblast enucleation-related gene transcription, enucleation defects and terminal maturation. Remarkably, FOXO3 ectopic expression increased wild type erythroblast maturation and enucleation suggesting that enhancing FOXO3 activity may improve RBCs production. Altogether these studies uncover FOXO3 as a novel regulator of erythroblast enucleation and terminal maturation suggesting FOXO3 modulation might be therapeutic in disorders with defective erythroid maturation.

  17. Characteristics of evolving models of care for arthritis: A key informant study

    Directory of Open Access Journals (Sweden)

    Veinot Paula

    2008-07-01

    Full Text Available Abstract Background The burden of arthritis is increasing in the face of diminishing health human resources to deliver care. In response, innovative models of care delivery are developing to facilitate access to quality care. Most models have developed in response to local needs with limited evaluation. The primary objective of this study is to a examine the range of models of care that deliver specialist services using a medical/surgical specialist and at least one other health care provider and b document the strengths and challenges of the identified models. A secondary objective is to identify key elements of best practice models of care for arthritis. Methods Semi-structured interviews were conducted with a sample of key informants with expertise in arthritis from jurisdictions with primarily publicly-funded health care systems. Qualitative data were analyzed using a constant comparative approach to identify common types of models of care, strengths and challenges of models, and key components of arthritis care. Results Seventy-four key informants were interviewed from six countries. Five main types of models of care emerged. 1 Specialized arthritis programs deliver comprehensive, multidisciplinary team care for arthritis. Two models were identified using health care providers (e.g. nurses or physiotherapists in expanded clinical roles: 2 triage of patients with musculoskeletal conditions to the appropriate services including specialists; and 3 ongoing management in collaboration with a specialist. Two models promoting rural access were 4 rural consultation support and 5 telemedicine. Key informants described important components of models of care including knowledgeable health professionals and patients. Conclusion A range of models of care for arthritis have been developed. This classification can be used as a framework for discussing care delivery. Areas for development include integration of care across the continuum, including primary

  18. Predicting establishment of non-native fishes in Greece: identifying key features

    Directory of Open Access Journals (Sweden)

    Christos Gkenas

    2015-11-01

    Full Text Available Non-native fishes are known to cause economic damage to human society and are considered a major threat to biodiversity loss in freshwater ecosystems. The growing concern about these impacts has driven to an investigation of the biological traits that facilitate the establishment of non-native fish. However, invalid assessment in choosing the appropriate statistical model can lead researchers to ambiguous conclusions. Here, we present a comprehensive comparison of traditional and alternative statistical methods for predicting fish invasions using logistic regression, classification trees, multicorrespondence analysis and random forest analysis to determine characteristics of successful and failed non-native fishes in Hellenic Peninsula through establishment. We defined fifteen categorical predictor variables with biological relevance and measures of human interest. Our study showed that accuracy differed according to the model and the number of factors considered. Among all the models tested, random forest and logistic regression performed best, although all approaches predicted non-native fish establishment with moderate to excellent results. Detailed evaluation among the models corresponded with differences in variables importance, with three biological variables (parental care, distance from nearest native source and maximum size and two variables of human interest (prior invasion success and propagule pressure being important in predicting establishment. The analyzed statistical methods presented have a high predictive power and can be used as a risk assessment tool to prevent future freshwater fish invasions in this region with an imperiled fish fauna.

  19. Identifying key components for an effective case report poster: an observational study.

    Science.gov (United States)

    Willett, Lisa L; Paranjape, Anuradha; Estrada, Carlos

    2009-03-01

    Residents demonstrate scholarly activity by presenting posters at academic meetings. Although recommendations from national organizations are available, evidence identifying which components are most important is not. To develop and test an evaluation tool to measure the quality of case report posters and identify the specific components most in need of improvement. Faculty evaluators reviewed case report posters and provided on-site feedback to presenters at poster sessions of four annual academic general internal medicine meetings. A newly developed ten-item evaluation form measured poster quality for specific components of content, discussion, and format (5-point Likert scale, 1 = lowest, 5 = highest). Evaluation tool performance, including Cronbach alpha and inter-rater reliability, overall poster scores, differences across meetings and evaluators and specific components of the posters most in need of improvement. Forty-five evaluators from 20 medical institutions reviewed 347 posters. Cronbach's alpha of the evaluation form was 0.84 and inter-rater reliability, Spearman's rho 0.49 (p tool provides empirical data to guide trainees as they prepare posters for presentation which may improve poster quality and enhance their scholarly productivity.

  20. Identifying Key Proteins in Hg Methylation Pathways of Desulfovibrio by Global Proteomics, Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Summers, Anne O. [Univ. of Georgia, Athens, GA (United States). Dept. of Microbiology; Miller, Susan M. [Univ. of California, San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry; Wall, Judy [Univ. of Missouri, Columbia, MO (United States). Dept. of Biochemistry; Lipton, Mary [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-06-18

    Elemental mercury, Hg(0) is a contaminant at many DOE sites, especially at Oak Ridge National Laboratory (ORNL) where the spread of spilled Hg and its effects on microbial populations have been monitored for decades. To explore the microbial interactions with Hg, we have devised a global proteomic approach capable of directly detecting Hg-adducts of proteins. This technique developed in the facultative anaerobe, Escherichia coli, allows us to identify the proteins most vulnerable to acute exposure to organomercurials phenyl- and ethyl-mercury (as surrogates for the highly neurotoxic methyl-Hg) (Polacco, et al, 2011). We have found >300 such proteins in all metabolic functional groups and cellular compartments; most are highly conserved and can serve as markers for acute Hg exposure (Zink, et al. 2016, in preparation). We have also discovered that acute Hg exposure severely disrupts thiol, iron and redox homeostases, and electrolyte balance (LaVoie, et al., 2015) Thus, we proposed to bring these techniques to bear on the central problem of identifying the cellular proteins involved in bacterial uptake and methylation of mercury and its release from the cell.

  1. Identifying Key Issues and Potential Solutions for Integrated Arrival, Departure, Surface Operations by Surveying Stakeholder Preferences

    Science.gov (United States)

    Aponso, Bimal; Coppenbarger, Richard A.; Jung, Yoon; Quon, Leighton; Lohr, Gary; O’Connor, Neil; Engelland, Shawn

    2015-01-01

    predictability and suggested several key attributes that were necessary to make the concept successful. The goals and objectives of the planned ATD-2 sub-project will incorporate the results of this stakeholder feedback.

  2. Identifying keys to success in clinical learning: a study of two interprofessional learning environments.

    Science.gov (United States)

    Laksov, Klara Bolander; Boman, Lena Engqvist; Liljedahl, Matilda; Björck, Erik

    2015-03-01

    The aim of this study was to study the intrinsic system behind interprofessional clinical learning environments. Two health care units were selected on the basis of having received a reward for best clinical learning organization. Interviews were carried out with health care staff/clinical supervisors from different professions. The interviews were transcribed and analysed according to qualitative content analysis, and categories and themes were identified. Analysis revealed two different systems of clinical learning environments. In one, the interplay between the structural aspects dominated, and in the other, the interplay between the cultural aspects dominated. An important similarity between the environments was that a defined role for students in the organization and interprofessional teamwork around supervision across professional borders was emphasized.

  3. Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments.

    Science.gov (United States)

    Noto, Jennifer M; Chopra, Abha; Loh, John T; Romero-Gallo, Judith; Piazuelo, M Blanca; Watson, Mark; Leary, Shay; Beckett, Amber C; Wilson, Keith T; Cover, Timothy L; Mallal, Simon; Israel, Dawn A; Peek, Richard M

    2017-09-18

    Helicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease. Whole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed. A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034). These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. A structured elicitation method to identify key direct risk factors for the management of natural resources.

    Science.gov (United States)

    Smith, Michael; Wallace, Ken; Lewis, Loretta; Wagner, Christian

    2015-11-01

    The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators), fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1) the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2) the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making.

  5. Combining ancestral sequence reconstruction with protein design to identify an interface hotspot in a key metabolic enzyme complex.

    Science.gov (United States)

    Holinski, Alexandra; Heyn, Kristina; Merkl, Rainer; Sterner, Reinhard

    2017-02-01

    It is important to identify hotspot residues that determine protein-protein interactions in interfaces of macromolecular complexes. We have applied a combination of ancestral sequence reconstruction and protein design to identify hotspots within imidazole glycerol phosphate synthase (ImGPS). ImGPS is a key metabolic enzyme complex, which links histidine and de novo purine biosynthesis and consists of the cyclase subunit HisF and the glutaminase subunit HisH. Initial fluorescence titration experiments showed that HisH from Zymomonas mobilis (zmHisH) binds with high affinity to the reconstructed HisF from the last universal common ancestor (LUCA-HisF) but not to HisF from Pyrobaculum arsenaticum (paHisF), which differ by 103 residues. Subsequent titration experiments with a reconstructed evolutionary intermediate linking LUCA-HisF and paHisF and inspection of the subunit interface of a contemporary ImGPS allowed us to narrow down the differences crucial for zmHisH binding to nine amino acids of HisF. Homology modeling and in silico mutagenesis studies suggested that at most two of these nine HisF residues are crucial for zmHisH binding. These computational results were verified by experimental site-directed mutagenesis, which finally enabled us to pinpoint a single amino acid residue in HisF that is decisive for high-affinity binding of zmHisH. Our work shows that the identification of protein interface hotspots can be very efficient when reconstructed proteins with different binding properties are included in the analysis. Proteins 2017; 85:312-321. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. On identifiability of certain latent class models.

    NARCIS (Netherlands)

    van Wieringen, W.N.

    2005-01-01

    Blischke [1962. Moment estimators for the parameters of a mixture of two binomial distributions. Ann. Math. Statist. 33, 444-454] studies a mixture of two binomials, a latent class model. In this article we generalize this model to a mixture of two products of binomials. We show when this generalize

  7. Key metrics for HFIR HEU and LEU models

    Energy Technology Data Exchange (ETDEWEB)

    Ilas, Germina [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Betzler, Benjamin R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chandler, David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Renfro, David G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Davidson, Eva E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-10-25

    This report compares key metrics for two fuel design models of the High Flux Isotope Reactor (HFIR). The first model represents the highly enriched uranium (HEU) fuel currently in use at HFIR, and the second model considers a low-enriched uranium (LEU) interim design fuel. Except for the fuel region, the two models are consistent, and both include an experiment loading that is representative of HFIR's current operation. The considered key metrics are the neutron flux at the cold source moderator vessel, the mass of 252Cf produced in the flux trap target region as function of cycle time, the fast neutron flux at locations of interest for material irradiation experiments, and the reactor cycle length. These key metrics are a small subset of the overall HFIR performance and safety metrics. They were defined as a means of capturing data essential for HFIR's primary missions, for use in optimization studies assessing the impact of HFIR's conversion from HEU fuel to different types of LEU fuel designs.

  8. Using the Delphi Technique to Identify Key Elements for Effective and Sustainable Visitor Use Planning Frameworks

    Directory of Open Access Journals (Sweden)

    Jessica P. Fefer

    2016-04-01

    Full Text Available Protected areas around the world receive nearly 800 billion visits/year, with international tourism continuing to increase. While protected areas provide necessary benefits to communities and visitors, the increased visitation may negatively impact the resource and the recreational experience, hence the need to manage visitor use in protected areas around the world. This research focused on obtaining information from experts to document their experiences utilizing one visitor use planning framework: Visitor Experience and Resource Protection (VERP. Using the Delphi Technique, 31 experts from seven regions around the world were asked to identify elements necessary for effective visitor management, as well as elements that facilitated or limited success when using VERP. Elements were categorized and rated in terms of importance. Scoring of the final categories was analyzed using Wilcoxon and Median non-parametric statistical tests. Results suggest that planning challenges stem from limitations in organizational capacity to support a long-term, adaptive management process, inferring that VERP may be sufficiently developed, but implementation capacity may not. The results can be used to refine existing frameworks, and to aid in the development of new recreation frameworks.

  9. Gene expression profiling in Entamoeba histolytica identifies key components in iron uptake and metabolism.

    Directory of Open Access Journals (Sweden)

    Nora Adriana Hernández-Cuevas

    Full Text Available Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron, low-iron medium (around 123 µM iron, iron-deficient medium (around 91 µM iron, and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite.

  10. Gene expression profiling in Entamoeba histolytica identifies key components in iron uptake and metabolism.

    Science.gov (United States)

    Hernández-Cuevas, Nora Adriana; Weber, Christian; Hon, Chung-Chau; Guillen, Nancy

    2014-01-01

    Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron), low-iron medium (around 123 µM iron), iron-deficient medium (around 91 µM iron), and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters) and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite.

  11. Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

    Science.gov (United States)

    Franic, Duska M; Haddock, Sarah M; Tucker, Leslie Tootle; Wooten, Nathan

    2008-01-01

    To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. Cross sectional. Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. Convenience sample of adult pharmacy consumers (n = 175). Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). 26 potential determinant attributes for pharmacy selection. 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.

  12. Identifying key soil cyanobacteria easy to isolate and culture for arid soil restoration

    Science.gov (United States)

    Roncero-Ramos, Beatriz; Ángeles Muñoz-Martín, M.; Chamizo, Sonia; Román, Raúl; Rodriguez-Caballero, Emilio; Mateo, Pilar; Cantón, Yolanda

    2017-04-01

    Drylands represent an important fraction of the Earth land's surface. Low cover of vascular plants characterizes these regions, and the large open areas among plants are often colonized by cyanobacteria, mosses, lichens, algae, bryophytes, bacteria and fungi, known as biocrusts. Because these communities are on or within the soil surface, they contribute to improve physicochemical properties of the uppermost soil layers and have important effects on soil fertility and stability, so they could play an important role on soil restoration. Cyanobacteria appear to be a cross component of biocrusts and they have been demonstrated to enhance water availability, soil fertility (fixing atmospheric C and N), and soil aggregation (thanks to their filamentous morphology and the exopolysaccharides they excrete), and significantly reduce water and wind erosion. Besides, they are able to tolerate high temperatures and UV radiation. All these features convert cyanobacteria in pioneer organisms capable of colonizing degraded soils and may be crucial in facilitating the succession of more developed organisms such as vascular plants. Therefore, the use of native cyanobacteria, already adapted to site environmental conditions, could guarantee a successful restoration approach of degraded soils. However, previous to their application for soil restoration, the most representative species inhabiting these soils should be identified. The objective of this study was to identify (morphologically and genetically) and isolate representative native cyanobacteria species from arid soils in SE Spain, characterized for being easily isolated and cultured with the aim of using them to inoculate degraded arid soil. We selected two study areas in Almería, SE Spain, where biocrust cover most of the open spaces between plants: El Cautivo experimental site located in the Tabernas desert and a limestone quarry located at the southeastern edge of the Gádor massif. The first site is characterized by

  13. Identifying plant traits: a key aspect for suitable species selection in ecological restoration of semiarid slopes

    Science.gov (United States)

    Bochet, Esther; García-Fayos, Patricio

    2017-04-01

    In the context of ecological restoration, one of the greatest challenges for practitioners and scientists is to select suitable species for revegetation purposes. In semiarid environments where restoration projects often fail, little attention has been paid so far to the contribution of plant traits to species success. The objective of this study was to (1) identify plant traits associated with species success on four roadside situations along an erosion-productivity gradient, and (2) to provide an ecological framework for selecting suitable species on the basis of their morphological and functional traits, applied to semiarid environments. We analyzed the association of 10 different plant traits with species success of 296 species surveyed on the four roadside situations in a semiarid region (Valencia, Spain). Plant traits included general plant traits (longevity, woodiness) and more specific root-, seed- and leaf-related traits (root type, sprouting ability, seed mucilage, seed mass, seed susceptibility to removal, specific leaf area and leaf dry matter content). All of them were selected according to the prevailing limiting ecogeomorphological processes acting along the erosion-productivity gradient. We observed strong shifts along the erosion-productivity gradient in the traits associated to species success. At the harshest end of the gradient, the most intensely eroded and driest one, species success was mainly associated to seed resistance to removal by runoff and to resistance to drought. At the opposite end of the gradient, the most productive one, species success was associated to a competitive-ruderal plant strategy (herbaceous successful species with high specific leaf area and low leaf dry matter content). Our study provides an ecologically-based approach for selecting suitable native species on the basis or their morphological and functional traits and supports a differential trait-based selection of species as regards roadslope type and aspect. In

  14. Fragmentation patterns of evergreen oak woodlands in Southwestern Iberia: identifying key spatial indicators.

    Science.gov (United States)

    Costa, Augusta; Madeira, Manuel; Lima Santos, José; Plieninger, Tobias; Seixas, Júlia

    2014-01-15

    Mediterranean evergreen oak woodlands (composed of Quercus suber L. and Quercus rotundifolia Lam.) are becoming increasingly fragmented in the human-modified landscapes of Southwestern Portugal and Spain. Previous studies have largely neglected to assess the spatial changes of oak woodlands in relation to their surrounding landscape matrix, and to characterize and quantify woodland boundaries and edges. The present study aims to fill this gap by analyzing fragmentation patterns of oak woodlands over a 50-year period (1958-2007) in three landscapes. Using archived aerial imagery from 1958, 1995 and 2007, for two consecutive periods (1958-1995 and 1995-2007), we calculated a set of landscape metrics to compare woodland fragmentation over time. Our results indicated a continuous woodland fragmentation characterized by their edge dynamics. From 1958 to 2007, the replacement of open farmland by shrubland and by new afforestation areas in the oak woodland landscape surrounding matrix, led to the highest values for edge contrast length trends of 5.0 and 12.3, respectively. Linear discriminant analysis was performed to delineate fragmented woodland structures and identify metric variables that characterize woodland spatial configuration. The edge contrast length with open farmland showed a strong correlation with F1 (correlations ranging between 0.55 and 0.98) and may be used as a proxy for oak woodland mixedness in landscape matrix. The edge dynamics of oak woodlands may result in different patterns of oak recruitment and therefore, its study may be helpful in highlighting future baselines for the sustainable management of oak woodlands.

  15. Model atmospheres - Tool for identifying interstellar features

    Science.gov (United States)

    Frisch, P. C.; Slojkowski, S. E.; Rodriguez-Bell, T.; York, D.

    1993-01-01

    Model atmosphere parameters are derived for 14 early A stars with rotation velocities, from optical spectra, in excess of 80 km/s. The models are compared with IUE observations of the stars in regions where interstellar lines are expected. In general, with the assumption of solar abundances, excellent fits are obtained in regions longward of 2580 A, and accurate interstellar equivalent widths can be derived using models to establish the continuum. The fits are poorer at shorter wavelengths, particularly at 2026-2062 A, where the stellar model parameters seem inadequate. Features indicating mass flows are evident in stars with known infrared excesses. In gamma TrA, variability in the Mg II lines is seen over the 5-year interval of these data, and also over timescales as short as 26 days. The present technique should be useful in systematic studies of episodic mass flows in A stars and for stellar abundance studies, as well as interstellar features.

  16. Mackinawite and greigite in ancient alkaline hydrothermal chimneys: Identifying potential key catalysts for emergent life

    Science.gov (United States)

    White, Lauren M.; Bhartia, Rohit; Stucky, Galen D.; Kanik, Isik; Russell, Michael J.

    2015-11-01

    One model for the emergence of life posits that ancient, low temperature, submarine alkaline hydrothermal vents, partly composed of iron-sulfides, were capable of catalyzing the synthesis of prebiotic organic molecules from CO2, H2 and CH4. Specifically, hydrothermal mackinawite (FeIIS) and greigite (FeIIFeIII2S4) have been highlighted in previous studies as analogs of the active centers of hydrogenase, ferredoxin, acetyl coenzyme-A synthase and carbon monoxide dehydrogenase featured in the biochemistry of certain autotrophic prokaryotes that occupy the base of the evolutionary tree. Despite the proposed importance of iron sulfide minerals and clusters in the synthesis of abiotic organic molecules, the mechanisms for the formation of these sulfides from solution and their preservation under the anoxic and low temperature (below 100 °C) conditions expected in off-axis submarine alkaline vent systems is not well understood (Bourdoiseau et al., 2011; Rickard and Luther, 2007). To rectify this, single hydrothermal chimneys were precipitated using a unique apparatus to simulate growth at hydrothermal vents of moderate temperature under supposed Hadean ocean-bottom conditions. Iron sulfide phases were observed through Raman spectroscopy at growth temperatures ranging from 40° to 80 °C. Fe(III)-containing mackinawite is confirmed to be present with mackinawite and greigite, supporting an FeIII-mackinawite intermediate mechanism for the transformation of mackinawite to greigite below 100 °C. Raman spectroscopy of the chimneys revealed a maximum yield of greigite at 75 °C. These results suggest abiotic production of catalytically active mackinawite and greigite are possible under early Earth hydrothermal conditions as well as on other wet, rocky worlds geochemically similar to the Earth.

  17. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal

    DEFF Research Database (Denmark)

    Madsen, Heidi Holst; Madsen, Dicte; Gauffriau, Marianne

    2016-01-01

    also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication. The objective is addressed in a literature review and a case study. The literature...... recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation...... review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI), incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed...

  18. Protocol for a thematic synthesis to identify key themes and messages from a palliative care research network.

    LENUS (Irish Health Repository)

    Nicholson, Emma

    2016-10-21

    Research networks that facilitate collaborative research are increasing both regionally and globally and such collaborations contribute greatly to knowledge transfer particularly in health research. The Palliative Care Research Network is an Irish-based network that seeks to create opportunities and engender a collaborative environment to encourage innovative research that is relevant for policy and practice. The current review outlines a methodology to identify cross-cutting messages to identify how dissemination outputs can be optimized to ensure that key messages from this research reaches all knowledge users.

  19. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

    DEFF Research Database (Denmark)

    Menzel, Tobias; Nähse-Kumpf, Viola; Kousholt, Arne Nedergaard;

    2011-01-01

    To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2......, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main...

  20. Selection of key terrain attributes for SOC model

    DEFF Research Database (Denmark)

    Greve, Mogens Humlekrog; Adhikari, Kabindra; Chellasamy, Menaka

    was selected, total 2,514,820 data mining models were constructed by 71 differences grid from 12m to 2304m and 22 attributes, 21 attributes derived by DTM and the original elevation. Relative importance and usage of each attributes in every model were calculated. Comprehensive impact rates of each attribute...... (standh) are the first three key terrain attributes in 5-attributes-model in all resolutions, the rest 2 of 5 attributes are Normal High (NormalH) and Valley Depth (Vall_depth) at the resolution finer than 40m, and Elevation and Channel Base (Chnl_base) coarser than 40m. The models at pixels size at 88m......As an important component of the global carbon pool, soil organic carbon (SOC) plays an important role in the global carbon cycle. SOC pool is the basic information to carry out global warming research, and needs to sustainable use of land resources. Digital terrain attributes are often use...

  1. Key management and encryption under the bounded storage model.

    Energy Technology Data Exchange (ETDEWEB)

    Draelos, Timothy John; Neumann, William Douglas; Lanzone, Andrew J.; Anderson, William Erik

    2005-11-01

    There are several engineering obstacles that need to be solved before key management and encryption under the bounded storage model can be realized. One of the critical obstacles hindering its adoption is the construction of a scheme that achieves reliable communication in the event that timing synchronization errors occur. One of the main accomplishments of this project was the development of a new scheme that solves this problem. We show in general that there exist message encoding techniques under the bounded storage model that provide an arbitrarily small probability of transmission error. We compute the maximum capacity of this channel using the unsynchronized key-expansion as side-channel information at the decoder and provide tight lower bounds for a particular class of key-expansion functions that are pseudo-invariant to timing errors. Using our results in combination with Dziembowski et al. [11] encryption scheme we can construct a scheme that solves the timing synchronization error problem. In addition to this work we conducted a detailed case study of current and future storage technologies. We analyzed the cost, capacity, and storage data rate of various technologies, so that precise security parameters can be developed for bounded storage encryption schemes. This will provide an invaluable tool for developing these schemes in practice.

  2. Development of Groundwater Modeling Capacity in Mongolia: Keys to Success

    Science.gov (United States)

    Anderson, M. T.; Valder, J. F.; Carter, J. M.

    2015-12-01

    Ulaanbaatar, the capital city of Mongolia, is totally dependent on groundwater for its municipal and industrial water supply. Water is drawn from a network of shallow wells in an alluvial aquifer along the Tuul River. Evidence, however, suggests that current water use and especially the projected water demand from a rapidly growing urban population, is not sustainable from existing water sources. In response, the Mongolia Ministry of Environment and the Mongolian Fresh Water Institute requested technical assistance on groundwater modeling through the U.S. Army Corps of Engineers to the U.S. Geological Survey (USGS). Scientists from the USGS-SD Water Science Center provided a workshop to Mongolian water experts on basic principles of groundwater modeling using MODFLOW. The purpose of the workshop was to bring together representatives from the Government of Mongolia, local universities, technical experts, and other key stakeholders to build in-country capacity in hydrogeology and groundwater modeling. A preliminary steady-state groundwater flow model was developed to simulate groundwater conditions in the Tuul River Basin and for use in water use decision-making. The model consisted of 2 layers, 226 rows, and 260 columns with uniform 500 meter grid spacing. The upper model layer represented the alluvial aquifer and the lower layer represented the underlying bedrock, which includes areas characterized by permafrost. Estimated groundwater withdrawal was 180 m3/day, and estimated recharge was 114 mm/yr. The model will be modified and updated by Mongolian scientists as more data are available. Ultimately the model will be used to assist managers in developing a sustainable water supply, for current use and changing climate scenarios. A key to success was developing in-country technical capacity and partnerships with the Mongolian University of Science and Technology, Mongolian Freshwater Institute, a non-profit organization, UNESCO, and the government of Mongolia.

  3. Are animal models relevant to key aspects of human parturition?

    Science.gov (United States)

    Mitchell, Bryan F; Taggart, Michael J

    2009-09-01

    Preterm birth remains the most serious complication of pregnancy and is associated with increased rates of infant death or permanent neurodevelopmental disability. Our understanding of the regulation of parturition remains inadequate. The scientific literature, largely derived from rodent animal models, suggests two major mechanisms regulating the timing of parturition: the withdrawal of the steroid hormone progesterone and a proinflammatory response by the immune system. However, available evidence strongly suggests that parturition in the human has significantly different regulators and mediators from those in most of the animal models. Our objectives are to critically review the data and concepts that have arisen from use of animal models for parturition and to rationalize the use of a new model. Many animal models have contributed to advances in our understanding of the regulation of parturition. However, we suggest that those animals dependent on progesterone withdrawal to initiate parturition clearly have a limitation to their translation to the human. In such models, a linear sequence of events (e.g., luteolysis, progesterone withdrawal, uterine activation, parturition) gives rise to the concept of a "trigger" mechanism. Conversely, we propose that human parturition may arise from the concomitant maturation of several systems in parallel. We have termed this novel concept "modular accumulation of physiological systems" (MAPS). We also emphasize the urgency to determine the precise role of the immune system in the process of parturition in situations other than intrauterine infection. Finally, we accentuate the need to develop a nonprimate animal model whose physiology is more relevant to human parturition. We suggest that the guinea pig displays several key physiological characteristics of gestation that more closely resemble human pregnancy than do currently favored animal models. We conclude that the application of novel concepts and new models are

  4. Secret Key and Private Key Constructions for Simple Multiterminal Source Models

    CERN Document Server

    Ye, Chunxuan

    2010-01-01

    We propose an approach for constructing secret and private keys based on the long-known Slepian-Wolf code, due to Wyner, for correlated sources connected by a virtual additive noise channel. Our work is motivated by results of Csisz\\'ar and Narayan which highlight innate connections between secrecy generation by multiple terminals that observe correlated source signals and Slepian-Wolf near-lossless data compression. Explicit procedures for such constructions and their substantiation are provided. The performance of low density parity check channel codes in devising a new class of secret keys is examined.

  5. The use of social networking platforms for sexual health promotion: identifying key strategies for successful user engagement.

    Science.gov (United States)

    Veale, Hilary J; Sacks-Davis, Rachel; Weaver, Emma Rn; Pedrana, Alisa E; Stoové, Mark A; Hellard, Margaret E

    2015-02-06

    Online social networking platforms such as Facebook and Twitter have grown rapidly in popularity, with opportunities for interaction enhancing their health promotion potential. Such platforms are being used for sexual health promotion but with varying success in reaching and engaging users. We aimed to identify Facebook and Twitter profiles that were able to engage large numbers of users, and to identify strategies used to successfully attract and engage users in sexual health promotion on these platforms. We identified active Facebook (n = 60) and Twitter (n = 40) profiles undertaking sexual health promotion through a previous systematic review, and assessed profile activity over a one-month period. Quantitative measures of numbers of friends and followers (reach) and social media interactions were assessed, and composite scores used to give profiles an 'engagement success' ranking. Associations between host activity, reach and interaction metrics were explored. Content of the top ten ranked Facebook and Twitter profiles was analysed using a thematic framework and compared with five poorly performing profiles to identify strategies for successful user engagement. Profiles that were able to successfully engage large numbers of users were more active and had higher levels of interaction per user than lower-ranked profiles. Strategies used by the top ten ranked profiles included: making regular posts/tweets (median 46 posts or 124 tweets/month for top-ranked profiles versus six posts or six tweets for poorly-performing profiles); individualised interaction with users (85% of top-ranked profiles versus 0% for poorly-performing profiles); and encouraging interaction and conversation by posing questions (100% versus 40%). Uploading multimedia material (80% versus 30%) and highlighting celebrity involvement (70% versus 10%) were also key strategies. Successful online engagement on social networking platforms can be measured through quantitative (user numbers and

  6. A global in vivo Drosophila RNAi screen identifies a key role of ceramide phosphoethanolamine for glial ensheathment of axons.

    Directory of Open Access Journals (Sweden)

    Aniket Ghosh

    Full Text Available Glia are of vital importance for all complex nervous system. One of the many functions of glia is to insulate and provide trophic and metabolic support to axons. Here, using glial-specific RNAi knockdown in Drosophila, we silenced 6930 conserved genes in adult flies to identify essential genes and pathways. Among our screening hits, metabolic processes were highly represented, and genes involved in carbohydrate and lipid metabolic pathways appeared to be essential in glia. One critical pathway identified was de novo ceramide synthesis. Glial knockdown of lace, a subunit of the serine palmitoyltransferase associated with hereditary sensory and autonomic neuropathies in humans, resulted in ensheathment defects of peripheral nerves in Drosophila. A genetic dissection study combined with shotgun high-resolution mass spectrometry of lipids showed that levels of ceramide phosphoethanolamine are crucial for axonal ensheathment by glia. A detailed morphological and functional analysis demonstrated that the depletion of ceramide phosphoethanolamine resulted in axonal defasciculation, slowed spike propagation, and failure of wrapping glia to enwrap peripheral axons. Supplementing sphingosine into the diet rescued the neuropathy in flies. Thus, our RNAi study in Drosophila identifies a key role of ceramide phosphoethanolamine in wrapping of axons by glia.

  7. Transcriptomics profiling of Indian mustard (Brassica juncea) under arsenate stress identifies key candidate genes and regulatory pathways.

    Science.gov (United States)

    Srivastava, Sudhakar; Srivastava, Ashish K; Sablok, Gaurav; Deshpande, Tejaswini U; Suprasanna, Penna

    2015-01-01

    Arsenic (As) is a non-essential element, a groundwater pollutant, whose uptake by plants produces toxic effects. The use of As-contaminated groundwater for irrigation can affect the crop productivity. Realizing the importance of the Brassica juncea as a crop plant in terms of oil-yield, there is a need to unravel mechanistic details of response to As stress and identify key functional genes and pathways. In this research, we studied time-dependent (4-96 h) transcriptome changes in roots and shoots of B. juncea under arsenate [As(V)] stress using Agilent platform. Among the whole transcriptome profiled genes, a total of 1,285 genes showed significant change in expression pattern upon As(V) exposure. The differentially expressed genes were categorized to various signaling pathways including hormones (jasmonate, abscisic acid, auxin, and ethylene) and kinases. Significant effects were also noticed on genes related to sulfur, nitrogen, CHO, and lipid metabolisms along with photosynthesis. Biochemical assays were conducted using specific inhibitors of glutathione and jasmonate biosynthesis, and kinases. The inhibitor studies revealed interconnection among sulfur metabolism, jasmonate, and kinase signaling pathways. In addition, various transposons also constituted a part of the altered transcriptome. Lastly, we profiled a set of key functional up- and down-regulated genes using real-time RT-PCR, which could act as an early indicators of the As stress.

  8. Culture Models to Define Key Mediators of Cancer Matrix Remodeling

    Directory of Open Access Journals (Sweden)

    Emily Suzanne Fuller

    2014-03-01

    Full Text Available High grade serous epithelial ovarian cancer (HG-SOC is one of the most devastating gynecological cancers affecting women worldwide, with a poor survival rate despite clinical treatment advances. HG-SOC commonly metastasizes within the peritoneal cavity, primarily to the mesothelial cells of the omentum which regulate an extracellular matrix (ECM rich in collagens type I, III and IV along with laminin, vitronectin and fibronectin. Cancer cells depend on their ability to penetrate and invade secondary tissue sites to spread, however a detailed understanding of the molecular mechanisms underlying these processes remain largely unknown. Given the high metastatic potential of HG-SOC and the associated poor clinical outcome, it is extremely important to identify the pathways and the components of which that are responsible for the progression of this disease. In-vitro methods of recapitulating human disease processes are the critical first step in such investigations. In this context, establishment of an in-vitro ‘tumor-like’ microenvironment, such as 3D culture, to study early disease and metastasis of human HG-SOC is an important and highly insightful method. In recent years many such methods have been established to investigate the adhesion and invasion of human ovarian cancer cell lines. The aim of this review is to summarize recent developments in ovarian cancer culture systems and their use to investigate clinically relevant findings concerning the key players in driving human HG-SOC.

  9. Valuing snorkeling visits to the Florida Keys with stated and revealed preference models.

    Science.gov (United States)

    Park, Timothy; Bowker, J M; Leeworthy, Vernon R

    2002-07-01

    Coastal coral reefs, especially in the Florida Keys, are declining at a disturbing rate. Marine ecologists and reef scientists have emphasized the importance of establishing nonmarket values of coral reefs to assess the cost effectiveness of coral reef management and remediation programs. The purpose of this paper is to develop a travel cost-contingent valuation model of demand for trips to the Florida Keys focusing on willingness to pay (WTP) to preserve the current water quality and health of the coral reefs. The stated and revealed preference models allow the marginal valuation of recreationists to adjust depending on current and planned trip commitments in valuing nonmarginal policy changes in recreational opportunities. The integrated model incorporates key factors for establishing baseline amenity values for tourist dive sites, including perceptions of reef quality and dive conditions, the role of substitute sites, and the quality and availability of tourist facilities and recreation opportunities. The travel cost and WTP model differ in identifying critical variables and provide insight into the adjustment of trip decisions across alternative destination sites and the valuation of trips. In contrast to the travel cost model, a measure of the availability of substitute sites and total recreation activities does not have a significant impact on WTP valuations reported by snorkelers. Snorkelers engage in a relatively focused set of activities, suggesting that these recreationists may not shift expenditures to other sites or other recreation activities in the Florida Keys when confronted with increased access costs for the snorkeling experience.

  10. A System-Level Throughput Model for Quantum Key Distribution

    Science.gov (United States)

    2015-09-17

    quantum mechanics to generate and distribute shared secret keying material. QKD systems generate and distribute key by progressing through a number of...communicate a seed to prime random number generation to construct a very large matrix used in the calculation of Privacy Amplification. We assume that... generate a desired number of final key bits. RQ7: What are the implications of altering the amount of Alice’s memory allocated for Quantum Exchange

  11. Key influences identified by first year undergraduate nursing students as impacting on the quality of clinical placement: A qualitative study.

    Science.gov (United States)

    Cooper, John; Courtney-Pratt, Helen; Fitzgerald, Mary

    2015-09-01

    Despite the fact that high quality clinical placement is an integral component of pre-registration nursing education for the development of the future nursing workforce, the literature identifies an ongoing struggle to 'get it right'. To examine qualitative data gathered through the Quality Clinical Placements Evaluation project to identify what pre-registration nursing students deemed helpful and not helpful influences on their first year Professional Experience Placement. A total of 553 first year undergraduate nursing students from 2010 to 2012 were enrolled in the programme and all were invited to complete a validated survey to measure the quality of their first clinical placement. A total of 361 completed surveys were returned. This paper examines the data provided through open-ended questions within the survey related to most helpful and least helpful aspects of their clinical experience. An inductive analysis approach using NVIVO allowed inherent areas to emerge from the raw data forming three key themes that influenced the experience of students. Feeling welcomed, individual versus team attitudes, and student expectations of supervising ward nurses were the themes identified that were perceived by the student as important to the success of learning and the quality of the experience overall. The findings echo previous research into the student experience of clinical placement; however the focus regarding the need for students to have a quality relationship with the supervising nurse is an area that warrants further exploration. Furthermore, we argue that students should be purposely engaged in the tertiary sector and provided guidance and strategies related to forming and maintaining relationships with those that supervise their clinical placement, in order to ensure consistent positive experiences. The outcomes from this study suggest that a missing component is teaching undergraduates how to manage relationships in clinical settings. Copyright © 2015

  12. Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Walls Dermot

    2006-09-01

    Full Text Available Abstract The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF remain elusive. Transforming Growth Factor beta 1(TGF-β1 is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549 in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF.

  13. Challenges of Identifying Communities with Shared Semantics in Enterprise Modeling

    NARCIS (Netherlands)

    Hoppenbrouwers, Stijn; Linden, D. van der

    2012-01-01

    In this paper we discuss the use and challenges of identifying communities with shared semantics in Enterprise Modeling. People tend to understand modeling meta-concepts (i.e., a modeling language’s constructs or types) in a certain way and can be grouped by this understanding. Having an insight int

  14. Sufficient conditions for rate-independent hysteresis in autoregressive identified models

    Science.gov (United States)

    Martins, Samir Angelo Milani; Aguirre, Luis Antonio

    2016-06-01

    This paper shows how hysteresis can be described using polynomial models and what are the sufficient conditions to be met by the model in order to have hysteresis. Such conditions are related to the model equilibria, to the forcing function and to certain term clusters in the polynomial models. The main results of the paper are used in the identification and analysis of nonlinear models estimated from data produced by a magneto-rheological damper (MRD) model with Bouc-Wen rate-independent hysteresis. A striking feature of the identified model is its simplicity and this could turn out to be a key factor in controller design.

  15. A Note on the Identifiability of Generalized Linear Mixed Models

    DEFF Research Database (Denmark)

    Labouriau, Rodrigo

    2014-01-01

    I present here a simple proof that, under general regularity conditions, the standard parametrization of generalized linear mixed model is identifiable. The proof is based on the assumptions of generalized linear mixed models on the first and second order moments and some general mild regularity ...... conditions, and, therefore, is extensible to quasi-likelihood based generalized linear models. In particular, binomial and Poisson mixed models with dispersion parameter are identifiable when equipped with the standard parametrization......I present here a simple proof that, under general regularity conditions, the standard parametrization of generalized linear mixed model is identifiable. The proof is based on the assumptions of generalized linear mixed models on the first and second order moments and some general mild regularity...

  16. Identifiability of Model Properties in Over-Parameterized Model Classes

    DEFF Research Database (Denmark)

    Jaeger, Manfred

    2013-01-01

    in the data. In this paper we make some initial steps to extend and adapt basic concepts of computational learnability and statistical identifiability to provide a foundation for investigating learnability in such broader contexts. We exemplify the use of the framework in three different applications...

  17. Identifiability of causal effect for a simple causal model

    Institute of Scientific and Technical Information of China (English)

    郑忠国; 张艳艳; 童行伟

    2002-01-01

    Counterfactual model is put forward to discuss the causal inference in the directed acyclic graph and its corresponding identifiability is thus studied with the ancillary information based on conditional independence. It is shown that the assumption of ignorability can be expanded to the assumption of replaceability,under which the causal efiects are identifiable.

  18. Toward Designing a Quantum Key Distribution Network Simulation Model

    Directory of Open Access Journals (Sweden)

    Miralem Mehic

    2016-01-01

    Full Text Available As research in quantum key distribution network technologies grows larger and more complex, the need for highly accurate and scalable simulation technologies becomes important to assess the practical feasibility and foresee difficulties in the practical implementation of theoretical achievements. In this paper, we described the design of simplified simulation environment of the quantum key distribution network with multiple links and nodes. In such simulation environment, we analyzed several routing protocols in terms of the number of sent routing packets, goodput and Packet Delivery Ratio of data traffic flow using NS-3 simulator.

  19. Intravital imaging of SRF and Notch signalling identifies a key role for EZH2 in invasive melanoma cells.

    Science.gov (United States)

    Manning, C S; Hooper, S; Sahai, E A

    2015-08-13

    The acquisition of cell motility is an early step in melanoma metastasis. Here we use intravital imaging of signalling reporter cell-lines combined with genome-wide transcriptional analysis to define signalling pathways and genes associated with melanoma metastasis. Intravital imaging revealed heterogeneous cell behaviour in vivo: <10% of cells were motile and both singly moving cells and streams of cells were observed. Motile melanoma cells had increased Notch- and SRF-dependent transcription. Subsequent genome-wide analysis identified an overlapping set of genes associated with high Notch and SRF activity. We identified EZH2, a histone methyltransferase in the Polycomb repressive complex 2, as a regulator of these genes. Heterogeneity of EZH2 levels is observed in melanoma models, and co-ordinated upregulation of genes positively regulated by EZH2 is associated with melanoma metastasis. EZH2 was also identified as regulating the amelanotic phenotype of motile cells in vivo by suppressing expression of the P-glycoprotein Oca2. Analysis of patient samples confirmed an inverse relationship between EZH2 levels and pigment. EZH2 targeting with siRNA and chemical inhibition reduced invasion in mouse and human melanoma cell lines. The EZH2-regulated genes KIF2C and KIF22 are required for melanoma cell invasion and important for lung colonization. We propose that heterogeneity in EZH2 levels leads to heterogeneous expression of a cohort of genes associated with motile behaviour including KIF2C and KIF22. EZH2-dependent increased expression of these genes promotes melanoma cell motility and early steps in metastasis.

  20. Identifying interacting pairs of sites in infinite range Ising models

    CERN Document Server

    Galves, Antonio; Takahashi, Daniel Yasumasa

    2010-01-01

    We consider Ising models (pairwise interaction Gibbs probability measures) in $\\Z^d$ with an infinite range potential. We address the problem of identifying pairs of interacting sites from a finite sample of independent realisations of the Ising model. The sample contains only the values assigned by the Ising model to a finite set of sites in $\\Z^d$. Our main result is an upperbound for the probability with our estimator to misidentify the pairs of interacting sites in this finite set.

  1. Key elements for implementing comprehensive health care models for persons with HIV: a stakeholder analysis.

    Science.gov (United States)

    Melchior, L A; Panter, A T; Larson, T A; Meredith, K L; Richardson-Nassif, K; Huba, G J

    2000-09-01

    A semistructured interview was conducted with 69 stakeholders in three university-based health care projects that were funded to provide an integrated continuum of care for persons living with HIV/AIDS. Data from the key informant interviews yielded composite indicators of familiarity with the service model, the importance of the elements in the service model, and the perceived quality of services provided by these innovative HIV service demonstration projects. Ratings of service quality were related to ratings of the respondent's knowledge of the service demonstration project, the importance of the various elements in the service continuum, and several indicators of stakeholder characteristics using the data modeling method of Exhaustive CHAID (Chi-squared Automatic Interaction Detector). The groups of stakeholders most likely to give the highest quality or success ratings for these projects are identified. The implications of these findings for developing collaborative and comprehensive service models for persons with HIV/AIDS are discussed.

  2. On the Identifiability of Transmission Dynamic Models for Infectious Diseases.

    Science.gov (United States)

    Lintusaari, Jarno; Gutmann, Michael U; Kaski, Samuel; Corander, Jukka

    2016-03-01

    Understanding the transmission dynamics of infectious diseases is important for both biological research and public health applications. It has been widely demonstrated that statistical modeling provides a firm basis for inferring relevant epidemiological quantities from incidence and molecular data. However, the complexity of transmission dynamic models presents two challenges: (1) the likelihood function of the models is generally not computable, and computationally intensive simulation-based inference methods need to be employed, and (2) the model may not be fully identifiable from the available data. While the first difficulty can be tackled by computational and algorithmic advances, the second obstacle is more fundamental. Identifiability issues may lead to inferences that are driven more by prior assumptions than by the data themselves. We consider a popular and relatively simple yet analytically intractable model for the spread of tuberculosis based on classical IS6110 fingerprinting data. We report on the identifiability of the model, also presenting some methodological advances regarding the inference. Using likelihood approximations, we show that the reproductive value cannot be identified from the data available and that the posterior distributions obtained in previous work have likely been substantially dominated by the assumed prior distribution. Further, we show that the inferences are influenced by the assumed infectious population size, which generally has been kept fixed in previous work. We demonstrate that the infectious population size can be inferred if the remaining epidemiological parameters are already known with sufficient precision.

  3. Similarity transformation approach to identifiability analysis of nonlinear compartmental models.

    Science.gov (United States)

    Vajda, S; Godfrey, K R; Rabitz, H

    1989-04-01

    Through use of the local state isomorphism theorem instead of the algebraic equivalence theorem of linear systems theory, the similarity transformation approach is extended to nonlinear models, resulting in finitely verifiable sufficient and necessary conditions for global and local identifiability. The approach requires testing of certain controllability and observability conditions, but in many practical examples these conditions prove very easy to verify. In principle the method also involves nonlinear state variable transformations, but in all of the examples presented in the paper the transformations turn out to be linear. The method is applied to an unidentifiable nonlinear model and a locally identifiable nonlinear model, and these are the first nonlinear models other than bilinear models where the reason for lack of global identifiability is nontrivial. The method is also applied to two models with Michaelis-Menten elimination kinetics, both of considerable importance in pharmacokinetics, and for both of which the complicated nature of the algebraic equations arising from the Taylor series approach has hitherto defeated attempts to establish identifiability results for specific input functions.

  4. PrEP for key populations in combination HIV prevention in Nairobi: a mathematical modelling study.

    Science.gov (United States)

    Cremin, Ide; McKinnon, Lyle; Kimani, Joshua; Cherutich, Peter; Gakii, Gloria; Muriuki, Festus; Kripke, Katharine; Hecht, Robert; Kiragu, Michael; Smith, Jennifer; Hinsley, Wes; Gelmon, Lawrence; Hallett, Timothy B

    2017-05-01

    The HIV epidemic in the population of Nairobi as a whole is in decline, but a concentrated sub-epidemic persists in key populations. We aimed to identify an optimal portfolio of interventions to reduce HIV incidence for a given budget and to identify the circumstances in which pre-exposure prophylaxis (PrEP) could be used in Nairobi, Kenya. A mathematical model was developed to represent HIV transmission in specific key populations (female sex workers, male sex workers, and men who have sex with men [MSM]) and among the wider population of Nairobi. The scale-up of existing interventions (condom promotion, antiretroviral therapy, and male circumcision) for key populations and the wider population as have occurred in Nairobi is represented. The model includes a detailed representation of a PrEP intervention and is calibrated to prevalence and incidence estimates specific to key populations and the wider population. In the context of a declining epidemic overall but with a large sub-epidemic in MSM and male sex workers, an optimal prevention portfolio for Nairobi should focus on condom promotion for male sex workers and MSM in particular, followed by improved antiretroviral therapy retention, earlier antiretroviral therapy, and male circumcision as the budget allows. PrEP for male sex workers could enter an optimal portfolio at similar levels of spending to when earlier antiretroviral therapy is included; however, PrEP for MSM and female sex workers would be included only at much higher budgets. If PrEP for male sex workers cost as much as US$500, average annual spending on the interventions modelled would need to be less than $3·27 million for PrEP for male sex workers to be excluded from an optimal portfolio. Estimated costs per infection averted when providing PrEP to all female sex workers regardless of their risk of infection, and to high-risk female sex workers only, are $65 160 (95% credible interval [CrI] $43 520-$90 250) and $10 920 (95% CrI $4700

  5. On the Identifiability of the Post-Nonlinear Causal Model

    CERN Document Server

    Zhang, Kun

    2012-01-01

    By taking into account the nonlinear effect of the cause, the inner noise effect, and the measurement distortion effect in the observed variables, the post-nonlinear (PNL) causal model has demonstrated its excellent performance in distinguishing the cause from effect. However, its identifiability has not been properly addressed, and how to apply it in the case of more than two variables is also a problem. In this paper, we conduct a systematic investigation on its identifiability in the two-variable case. We show that this model is identifiable in most cases; by enumerating all possible situations in which the model is not identifiable, we provide sufficient conditions for its identifiability. Simulations are given to support the theoretical results. Moreover, in the case of more than two variables, we show that the whole causal structure can be found by applying the PNL causal model to each structure in the Markov equivalent class and testing if the disturbance is independent of the direct causes for each va...

  6. Identifiability analysis of the CSTR river water quality model.

    Science.gov (United States)

    Chen, J; Deng, Y

    2006-01-01

    Conceptual river water quality models are widely known to lack identifiability. The causes for that can be due to model structure errors, observational errors and less frequent samplings. Although significant efforts have been directed towards better identification of river water quality models, it is not clear whether a given model is structurally identifiable. Information is also limited regarding the contribution of different unidentifiability sources. Taking the widely applied CSTR river water quality model as an example, this paper presents a theoretical proof that the CSTR model is indeed structurally identifiable. Its uncertainty is thus dominantly from observational errors and less frequent samplings. Given the current monitoring accuracy and sampling frequency, the unidentifiability from sampling frequency is found to be more significant than that from observational errors. It is also noted that there is a crucial sampling frequency between 0.1 and 1 day, over which the simulated river system could be represented by different illusions and the model application could be far less reliable.

  7. Exploring key factors in online shopping with a hybrid model.

    Science.gov (United States)

    Chen, Hsiao-Ming; Wu, Chia-Huei; Tsai, Sang-Bing; Yu, Jian; Wang, Jiangtao; Zheng, Yuxiang

    2016-01-01

    Nowadays, the web increasingly influences retail sales. An in-depth analysis of consumer decision-making in the context of e-business has become an important issue for internet vendors. However, factors affecting e-business are complicated and intertwined. To stimulate online sales, understanding key influential factors and causal relationships among the factors is important. To gain more insights into this issue, this paper introduces a hybrid method, which combines the Decision Making Trial and Evaluation Laboratory (DEMATEL) with the analytic network process, called DANP method, to find out the driving factors that influence the online business mostly. By DEMATEL approach the causal graph showed that "online service" dimension has the highest degree of direct impact on other dimensions; thus, the internet vendor is suggested to made strong efforts on service quality throughout the online shopping process. In addition, the study adopted DANP to measure the importance of key factors, among which "transaction security" proves to be the most important criterion. Hence, transaction security should be treated with top priority to boost the online businesses. From our study with DANP approach, the comprehensive information can be visually detected so that the decision makers can spotlight on the root causes to develop effectual actions.

  8. Data Mining and Pattern Recognition Models for Identifying Inherited Diseases

    DEFF Research Database (Denmark)

    Iddamalgoda, Lahiru; Das, Partha S; Aponso, Achala;

    2016-01-01

    Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately...... prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods...

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

    Science.gov (United States)

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

    2016-10-01

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

  10. Key Elements of the Tutorial Support Management Model

    Science.gov (United States)

    Lynch, Grace; Paasuke, Philip

    2011-01-01

    In response to an exponential growth in enrolments the "Tutorial Support Management" (TSM) model has been adopted by Open Universities Australia (OUA) after a two-year project on the provision of online tutor support in first year, online undergraduate units. The essential focus of the TSM model was the development of a systemic approach…

  11. Parameter Identifiability of Ship Manoeuvring Modeling Using System Identification

    Directory of Open Access Journals (Sweden)

    Weilin Luo

    2016-01-01

    Full Text Available To improve the feasibility of system identification in the prediction of ship manoeuvrability, several measures are presented to deal with the parameter identifiability in the parametric modeling of ship manoeuvring motion based on system identification. Drift of nonlinear hydrodynamic coefficients is explained from the point of view of regression analysis. To diminish the multicollinearity in a complicated manoeuvring model, difference method and additional signal method are employed to reconstruct the samples. Moreover, the structure of manoeuvring model is simplified based on correlation analysis. Manoeuvring simulation is performed to demonstrate the validity of the measures proposed.

  12. Key Challenges and Potential Urban Modelling Opportunities in ...

    African Journals Online (AJOL)

    Chris Wray

    monitoring and guiding urban spatial planning and development. ... and social system functions, urban modelling has evolved from simple ... careful long-term planning aligned with the national vision and other strategic perspectives' (GPC,.

  13. Swift residue-screening identifies key N-glycosylated asparagines sufficient for surface expression of neuroglycoprotein Lingo-1.

    Science.gov (United States)

    Zhong, Xiaotian; Pocas, Jennifer; Liu, Yan; Wu, Paul W; Mosyak, Lidia; Somers, Will; Kriz, Ron

    2009-03-18

    Advances in genomics and proteomics have generated the needs for the efficient identification of key residues for structure and function of target proteins. Here we report the utilization of a new residue-screening approach, which combines a mammalian high-throughput transient expression system with a PCR-based expression cassette, for the study of the post-translational modification. Applying this approach results in a quick identification of essential N-glycosylation sites of a heavily glycosylated neuroglycoprotein Lingo-1, which are sufficient for the support of its surface expression. These key N-glycosylated sites uniquely locate on the concave surface of the elongated arc-shape structure of the leucine-rich repeat domain. The swift residue-screening approach may provide a new strategy for structural and functional analysis.

  14. The shell model approach: Key to hadron structure

    Energy Technology Data Exchange (ETDEWEB)

    Lipkin, H.J. (Weizmann Inst. of Science, Rehovoth (Israel). Dept. of Nuclear Physics)

    1989-08-14

    A shell model approach leads to a simple constituent quark model for hadron structure in which mesons and baryons consist only of constituent quarks. Hadron masses are the sums of the constituent quark effective masses and a hyperfine interaction inversely proportional to the product of these same masses. Hadron masses and magnetic moments are related by the assumption that the same effective mass parameter appears in the additive mass term, the hyperfine interaction, and the quark magnetic moment, both in mesons and baryons. The analysis pinpoints the physical assumptions needed for each relation and gives two new mass relations. Application to weak decays and recent polarized EMC data confirms conclusions previously obtained that the current quark contribution to the spin structure of the proton vanishes, but without need for the questionable assumption of SU(3) symmetry relating hyperon decays and proton structure. SU(3) symmetry breaking is clarified. 24 refs.

  15. Scattering as a key to improved room acoustic computer modelling

    DEFF Research Database (Denmark)

    Rindel, Jens Holger; Christensen, Claus Lynge

    1996-01-01

    It has been known for a long time that surface scattering plays a very important role in room acoustics. With room acoustic computer models like ODEON it is possible to study the influence of scattering coefficients, which can be assigned to the surfaces of the room. In the latest version...... of the program an additional effect has been modelled, namely the attenuation of sound due to diffraction, which is particularly pronounced for small surfaces, low frequencies and long reflecting paths. The present paper describes a parameter study of how to optimize the choice of the number of rays...... room acoustic parameters. Results from two different halls have shown that a relative low number of rays are sufficient for reliable and stable calculation results. The optimum value of the transition order is two or three. The inclusion of diffraction effect leads to clearly improved results....

  16. A model for revocation forecasting in public-key infrastructures

    OpenAIRE

    Hernández Gañan, Carlos; Mata Diaz, Jorge; Muñoz Tapia, José Luis; Esparza Martín, Óscar; Alins Delgado, Juan José

    2015-01-01

    One of the hardest tasks of a certification infrastructure is to manage revocation. This process consists in collecting and making the revocation status of certificates available to users. Research on this topic has focused on the trade-offs that different revocation mechanisms offer. Much less effort has been conducted to understand and model real-world revocation processes. For this reason, in this paper, we present a novel analysis of real-world collected revocation data and we propose a r...

  17. IDENTIFYING THE PARAMETERS OF THE MATHEMATICAL EXPENDITURE SYSTEM MODEL

    Directory of Open Access Journals (Sweden)

    ANA-PETRINA PĂUN

    2013-10-01

    Full Text Available This chapter describes an optimum regulation model for the public expenditures system in Romania. The aim of this work is to design an optimal control system of public expenditures in Romania. It contains an offline identification of the total public expenditures system in Romania for a timespan of 15 years. The total public expenditures system is a MISO type one (Multiple Input – Single Output and is identified by the use of the lowest foursquare applied on an OE (Output Error type model.

  18. Accessing key steps of human tumor progression in vivo by using an avian embryo model

    Science.gov (United States)

    Hagedorn, Martin; Javerzat, Sophie; Gilges, Delphine; Meyre, Aurélie; de Lafarge, Benjamin; Eichmann, Anne; Bikfalvi, Andreas

    2005-02-01

    Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening. angiogenesis | animal model alternatives | glioblastoma

  19. Identifying gene regulatory network rewiring using latent differential graphical models.

    Science.gov (United States)

    Tian, Dechao; Gu, Quanquan; Ma, Jian

    2016-09-30

    Gene regulatory networks (GRNs) are highly dynamic among different tissue types. Identifying tissue-specific gene regulation is critically important to understand gene function in a particular cellular context. Graphical models have been used to estimate GRN from gene expression data to distinguish direct interactions from indirect associations. However, most existing methods estimate GRN for a specific cell/tissue type or in a tissue-naive way, or do not specifically focus on network rewiring between different tissues. Here, we describe a new method called Latent Differential Graphical Model (LDGM). The motivation of our method is to estimate the differential network between two tissue types directly without inferring the network for individual tissues, which has the advantage of utilizing much smaller sample size to achieve reliable differential network estimation. Our simulation results demonstrated that LDGM consistently outperforms other Gaussian graphical model based methods. We further evaluated LDGM by applying to the brain and blood gene expression data from the GTEx consortium. We also applied LDGM to identify network rewiring between cancer subtypes using the TCGA breast cancer samples. Our results suggest that LDGM is an effective method to infer differential network using high-throughput gene expression data to identify GRN dynamics among different cellular conditions.

  20. Monitor key parameters of winter wheat using Crop model

    Science.gov (United States)

    Jibo, Yue; Haikuan, Feng; Xiudong, Qi

    2016-11-01

    Estimation of biomass, canopy cover and yield is very important to agricultural decision Precision Farming. During the winter wheat growing season of 2013/2014, field measurements were conducted at Yangling District, Shaanxi Province at the jointing stage, heading stage and filling stage. AquaCrop model and Particle swarm optimization algorithm was used to find the global optimal simulation when the intermediate variable was the biomass. Through the simulation for each of the experimental data, biomass, canopy coverage and soil moisture were verification by ground measurements. Based on 8 sets of data, the simulation accuracy was calculated. The RMSE, nRMSE, MAE and R2 between simulation and measured biomass were 1.06 ton/ha, 11.92%, 0.90 ton/ha and 0.92. The RMSE, nRMSE, MAE and R2 between simulation and measured canopy cover were 8.92%, 9.84%, 7.84% and 0.66, respectively. The simulation results show that the AquaCrop model can help the decision making of winter wheat field in arid areas.

  1. USING THE PARETO DIAGRAM AND FMEA (FAILURE MODE AND EFFECTS ANALYSIS TO IDENTIFY KEY DEFECTS IN A PRODUCT

    Directory of Open Access Journals (Sweden)

    Michał ZASADZIEŃ

    2014-10-01

    Full Text Available The article presents the results of studies conducted in a company manufacturing aluminium forgings for the automotive industry. The aim of the research was to identify the defects which form during the production process as well as the locations and causes of their occurrence. Selected quality management tools were used in the process. Based on the FMEA and the costs generated by the identified defects, a hierarchy of them was created for the company along with a proposal of improvements in case of the most significant ones in order to reduce their number and increase the detection efficiency.

  2. Rock thermal conductivity as key parameter for geothermal numerical models

    Science.gov (United States)

    Di Sipio, Eloisa; Chiesa, Sergio; Destro, Elisa; Galgaro, Antonio; Giaretta, Aurelio; Gola, Gianluca; Manzella, Adele

    2013-04-01

    The geothermal energy applications are undergoing a rapid development. However, there are still several challenges in the successful exploitation of geothermal energy resources. In particular, a special effort is required to characterize the thermal properties of the ground along with the implementation of efficient thermal energy transfer technologies. This paper focuses on understanding the quantitative contribution that geosciences can receive from the characterization of rock thermal conductivity. The thermal conductivity of materials is one of the main input parameters in geothermal modeling since it directly controls the steady state temperature field. An evaluation of this thermal property is required in several fields, such as Thermo-Hydro-Mechanical multiphysics analysis of frozen soils, designing ground source heat pumps plant, modeling the deep geothermal reservoirs structure, assessing the geothermal potential of subsoil. Aim of this study is to provide original rock thermal conductivity values useful for the evaluation of both low and high enthalpy resources at regional or local scale. To overcome the existing lack of thermal conductivity data of sedimentary, igneous and metamorphic rocks, a series of laboratory measurements has been performed on several samples, collected in outcrop, representative of the main lithologies of the regions included in the VIGOR Project (southern Italy). Thermal properties tests were carried out both in dry and wet conditions, using a C-Therm TCi device, operating following the Modified Transient Plane Source method.Measurements were made at standard laboratory conditions on samples both water saturated and dehydrated with a fan-forced drying oven at 70 ° C for 24 hr, for preserving the mineral assemblage and preventing the change of effective porosity. Subsequently, the samples have been stored in an air-conditioned room while bulk density, solid volume and porosity were detected. The measured thermal conductivity

  3. Identifying potential strategies in the key sectors of China’s food chain to implement sustainable phosphorus management

    NARCIS (Netherlands)

    Li, Guohua; Huang, Gaoqiang; Li, Haigang; Ittersum, van M.K.; Leffelaar, P.A.; Zhang, Fusuo

    2016-01-01

    High extraction of phosphate reserves and low phosphorus utilization efficiency in the food chain in China result in large P losses and serious environmental pollution. The P fertilizer industry, soil P surplus, livestock manure P and wastewater P recycling have been identified as the priority

  4. Key Affective Behaviors of Students as Identified by a Select Group of Secondary School Teachers Using the SCANS Categories.

    Science.gov (United States)

    McNabb, Jeffrey G.

    1997-01-01

    Secondary teachers (n=58, 40% response) identified student behaviors for the five affective areas of the Secretary's Commission on Achieving Necessary Skills (SCANS) report (responsibility, self-esteem, sociability, self-management, integrity/honesty). The list of behaviors could provide a foundation for secondary schools implementing…

  5. Compartmental analysis of dynamic nuclear medicine data: models and identifiability

    Science.gov (United States)

    Delbary, Fabrice; Garbarino, Sara; Vivaldi, Valentina

    2016-12-01

    Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how nonlinear regularization schemes can be applied to obtain numerical estimates of the tracer coefficients in the case of nuclear medicine data corresponding to brain, liver and kidney physiology.

  6. Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gaora Peadar Ó

    2010-10-01

    Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

  7. Empirical model of the composition of the Venus ionosphere Repeatable characteristics and key features not modeled

    Science.gov (United States)

    Taylor, H. A., Jr.; Mayr, H. G.; Niemann, H. B.; Larson, J.

    1985-01-01

    In-situ measurements of positive ion composition of the ionosphere of Venus are combined in an empirical model which is a key element for the Venus International Reference Atmosphere (VIRA) model. The ion data are obtained from the Pioneer Venus Orbiter Ion Mass Spectrometer (OIMS) which obtained daily measurements beginning in December 1978 and extending to July 1980 when the uncontrolled rise of satellite periapsis height precluded further measurements in the main body of the ionosphere. For this period, measurements of 12 ion species are sorted into altitude and local time bins with altitude extending from 150 to 1000 km. The model results exhibit the appreciable nightside ionosphere found at Venus, the dominance of atomic oxygen ions in the dayside upper ionosphere and the increase in prominence of atomic oxygen and deuterium ions on the nightside. Short term variations, such as the abrupt changes observed in the ionopause, cannot be represented in the model.

  8. Re-orienting a remote acute care model towards a primary health care approach: key enablers.

    Science.gov (United States)

    Carroll, Vicki; Reeve, Carole A; Humphreys, John S; Wakerman, John; Carter, Maureen

    2015-01-01

    The objective of this study was to identify the key enablers of change in re-orienting a remote acute care model to comprehensive primary healthcare delivery. The setting of the study was a 12-bed hospital in Fitzroy Crossing, Western Australia. Individual key informant, in-depth interviews were completed with five of six identified senior leaders involved in the development of the Fitzroy Valley Health Partnership. Interviews were recorded and transcripts were thematically analysed by two investigators for shared views about the enabling factors strengthening primary healthcare delivery in a remote region of Australia. Participants described theestablishment of a culturally relevant primary healthcare service, using a community-driven, 'bottom up' approach characterised by extensive community participation. The formal partnership across the government and community controlled health services was essential, both to enable change to occur and to provide sustainability in the longer term. A hierarchy of major themes emerged. These included community participation, community readiness and desire for self-determination; linkages in the form of a government community controlled health service partnership; leadership; adequate infrastructure; enhanced workforce supply; supportive policy; and primary healthcare funding. The strong united leadership shown by the community and the health service enabled barriers to be overcome and it maximised the opportunities provided by government policy changes. The concurrent alignment around a common vision enabled implementation of change. The key principle learnt from this study is the importance of community and health service relationships and local leadership around a shared vision for the re-orientation of community health services.

  9. Identifying Student and Teacher Difficulties in Interpreting Atomic Spectra Using a Quantum Model of Emission and Absorption of Radiation

    Science.gov (United States)

    Savall-Alemany, Francisco; Domènech-Blanco, Josep Lluís; Guisasola, Jenaro; Martínez-Torregrosa, Joaquín

    2016-01-01

    Our study sets out to identify the difficulties that high school students, teachers, and university students encounter when trying to explain atomic spectra. To do so, we identify the key concepts that any quantum model for the emission and absorption of electromagnetic radiation must include to account for the gas spectra and we then design two…

  10. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal - a case study from health science.

    Science.gov (United States)

    Madsen, Heidi Holst; Madsen, Dicte; Gauffriau, Marianne

    2016-01-01

    Unique identifiers (UID) are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case with publications from the health sciences. We evaluate the matching process based on information about coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match keys. We analyze this information to detect errors, if any, in the matching process. As an example we also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication.  The objective is addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI), incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication. The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of UIDs may become

  11. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal – a case study from health science

    Science.gov (United States)

    Madsen, Heidi Holst; Madsen, Dicte; Gauffriau, Marianne

    2016-01-01

    Unique identifiers (UID) are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case with publications from the health sciences. We evaluate the matching process based on information about coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match keys. We analyze this information to detect errors, if any, in the matching process. As an example we also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication.  The objective is addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI), incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication. The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of UIDs may become

  12. RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

    Science.gov (United States)

    Ariani, Andrea; Di Baccio, Daniela; Romeo, Stefania; Lombardi, Lara; Andreucci, Andrea; Lux, Alexander; Horner, David Stephen; Sebastiani, Luca

    2015-01-01

    Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE) genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated) and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO) terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1) probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS) that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

  13. RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

    Directory of Open Access Journals (Sweden)

    Andrea Ariani

    Full Text Available Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1 probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

  14. Identifying rock blocks based on hierarchical rock-mass structure model

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Rock-masses are divided into many closed blocks by deterministic and stochastic discontinuities and engineering interfaces in complex rock-mass engineering. Determining the sizes, shapes, and adjacent relations of blocks is important for stability analysis of fractured rock masses. Here we propose an algorithm for identifying spatial blocks based on a hierarchical 3D Rock-mass Structure Model (RSM). First, a model is built composed of deterministic discontinuities, engineering interfaces, and the earth’s surface, and the deterministic blocks surrounded by these interfaces are traced. Then, in each deter-ministic block, a network model of stochastic discontinuities is built and the stochastic blocks are traced. Building a unitary wire frame that connects all interfaces seamlessly is the key for our algorithm to identify the above two kinds of blocks. Using this algorithm, geometric models can be built for block theory, discrete element method, and discontinuous deformation analysis.

  15. A new process sensitivity index to identify important system processes under process model and parametric uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Heng [Pacific Northwest National Laboratory, Richland Washington USA; Ye, Ming [Department of Scientific Computing, Florida State University, Tallahassee Florida USA; Walker, Anthony P. [Environmental Sciences Division and Climate Change Science Institute, Oak Ridge National Laboratory, Oak Ridge Tennessee USA; Chen, Xingyuan [Pacific Northwest National Laboratory, Richland Washington USA

    2017-04-01

    Hydrological models are always composed of multiple components that represent processes key to intended model applications. When a process can be simulated by multiple conceptual-mathematical models (process models), model uncertainty in representing the process arises. While global sensitivity analysis methods have been widely used for identifying important processes in hydrologic modeling, the existing methods consider only parametric uncertainty but ignore the model uncertainty for process representation. To address this problem, this study develops a new method to probe multimodel process sensitivity by integrating the model averaging methods into the framework of variance-based global sensitivity analysis, given that the model averaging methods quantify both parametric and model uncertainty. A new process sensitivity index is derived as a metric of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and model parameters. For demonstration, the new index is used to evaluate the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that converting precipitation to recharge, and the geology process is also simulated by two models of different parameterizations of hydraulic conductivity; each process model has its own random parameters. The new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.

  16. Sleeping Beauty mouse models identify candidate genes involved in gliomagenesis.

    Science.gov (United States)

    Vyazunova, Irina; Maklakova, Vilena I; Berman, Samuel; De, Ishani; Steffen, Megan D; Hong, Won; Lincoln, Hayley; Morrissy, A Sorana; Taylor, Michael D; Akagi, Keiko; Brennan, Cameron W; Rodriguez, Fausto J; Collier, Lara S

    2014-01-01

    Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma.

  17. Identifying and modeling the structural discontinuities of human interactions

    Science.gov (United States)

    Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

    2017-04-01

    The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales.

  18. Integrated Analysis of DNA Methylation and mRNA Expression Profiles to Identify Key Genes in Severe Oligozoospermia

    Directory of Open Access Journals (Sweden)

    Zhiming Li

    2017-05-01

    Full Text Available Severe oligozoospermia (SO is a complex disorder, whose etiology is the combined effect of genetic factors and epigenetic conditions. In this study, we examined DNA methylation and mRNA expression status in a set of testicular tissues of SO patients (n = 3, and compared methylated data with those derived from obstructive azoospermia (OA patients (n = 3 with normal spermatogenesis phenotype. We identified 1,960 differentially methylated CpG sites showing significant alterations in SO vs. OA using the Illumina Infinium HumanMethylation450 bead array. By integrating above DNA methylation data and mRNA expression results, we totally identified 72 methylated CpG sites located in 65 genes with anti-correlation between DNA methylation and mRNA expression. Integrated pathways analysis indicates that these genes are involved in response to hormone stimulus, activation of protein kinase activity, and apoptotic process, among others. We also observed some genes with inversely correlated difference is novel in male infertility field, including PTPRN2, EPHX1, SERPINB9, SLIT3, etc. Our results lay a groundwork for further biological study of SO. Moreover, we generated a workflow for integrated analysis of DNA methylation and mRNA expression, which is expandable to other study types.

  19. RNA-Seq analysis identifies key genes associated with haustorial development in the root hemiparasite Santalum album

    Directory of Open Access Journals (Sweden)

    Xinhua eZhang

    2015-09-01

    Full Text Available Santalum album (sandalwood is one of the economically important plant species in the Santalaceae for its production of highly valued perfume oils. Sandalwood is also a hemiparasitic tree that obtains some of its water and simple nutrients by tapping into other plants through haustoria which are highly specialized organs in parasitic angiosperms. However, an understanding of the molecular mechanisms involved in haustorium development is limited. In this study, RNA sequencing (RNA-seq analyses were performed to identify changes in gene expression and metabolic pathways associated with the development of the S. album haustorium. A total of 56,011 non-redundant contigs with a mean contig size of 618 bp were obtained by de novo assembly of the transcriptome of haustoria and non-haustorial seedling roots. A substantial number of the identified differentially expressed genes were involved in cell wall metabolism and protein metabolism, as well as mitochondrial electron transport functions. Phytohormone-mediated regulation might play an important role during haustorial development. Especially, auxin signaling is likely to be essential for haustorial initiation, and genes related to cytokinin and gibberellin biosynthesis and metabolism are involved in haustorial development. Our results suggest that genes encoding nodulin-like proteins may be important for haustorial morphogenesis in S. album. The obtained sequence data will become a rich resource for future research in this interesting species. This information improves our understanding of haustorium development in root hemiparasitic species and will allow further exploration of the detailed molecular mechanisms underlying plant parasitism.

  20. From spatially variable streamflow to distributed hydrological models: Analysis of key modeling decisions

    Science.gov (United States)

    Fenicia, Fabrizio; Kavetski, Dmitri; Savenije, Hubert H. G.; Pfister, Laurent

    2016-02-01

    This paper explores the development and application of distributed hydrological models, focusing on the key decisions of how to discretize the landscape, which model structures to use in each landscape element, and how to link model parameters across multiple landscape elements. The case study considers the Attert catchment in Luxembourg—a 300 km2 mesoscale catchment with 10 nested subcatchments that exhibit clearly different streamflow dynamics. The research questions are investigated using conceptual models applied at hydrologic response unit (HRU) scales (1-4 HRUs) on 6 hourly time steps. Multiple model structures are hypothesized and implemented using the SUPERFLEX framework. Following calibration, space/time model transferability is tested using a split-sample approach, with evaluation criteria including streamflow prediction error metrics and hydrological signatures. Our results suggest that: (1) models using geology-based HRUs are more robust and capture the spatial variability of streamflow time series and signatures better than models using topography-based HRUs; this finding supports the hypothesis that, in the Attert, geology exerts a stronger control than topography on streamflow generation, (2) streamflow dynamics of different HRUs can be represented using distinct and remarkably simple model structures, which can be interpreted in terms of the perceived dominant hydrologic processes in each geology type, and (3) the same maximum root zone storage can be used across the three dominant geological units with no loss in model transferability; this finding suggests that the partitioning of water between streamflow and evaporation in the study area is largely independent of geology and can be used to improve model parsimony. The modeling methodology introduced in this study is general and can be used to advance our broader understanding and prediction of hydrological behavior, including the landscape characteristics that control hydrologic response, the

  1. Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis

    Science.gov (United States)

    Yoshimi, N; Futamura, T; Bergen, S E; Iwayama, Y; Ishima, T; Sellgren, C; Ekman, C J; Jakobsson, J; Pålsson, E; Kakumoto, K; Ohgi, Y; Yoshikawa, T; Landén, M; Hashimoto, K

    2016-01-01

    Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD. PMID:26782057

  2. An Identifiable State Model To Describe Light Intensity Influence on Microalgae Growth.

    Science.gov (United States)

    Bernardi, A; Perin, G; Sforza, E; Galvanin, F; Morosinotto, T; Bezzo, F

    2014-04-23

    Despite the high potential as feedstock for the production of fuels and chemicals, the industrial cultivation of microalgae still exhibits many issues. Yield in microalgae cultivation systems is limited by the solar energy that can be harvested. The availability of reliable models representing key phenomena affecting algae growth may help designing and optimizing effective production systems at an industrial level. In this work the complex influence of different light regimes on seawater alga Nannochloropsis salina growth is represented by first principles models. Experimental data such as in vivo fluorescence measurements are employed to develop the model. The proposed model allows description of all growth curves and fluorescence data in a reliable way. The model structure is assessed and modified in order to guarantee the model identifiability and the estimation of its parametric set in a robust and reliable way.

  3. A Simple Model for Identifying Critical Structures in Atrial Fibrillation

    CERN Document Server

    Christensen, Kim; Peters, Nicholas S

    2014-01-01

    Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wavefront propagation on a structure mimicking the branching network architecture of heart muscle and show how AF emerges spontaneously as age-related parameters change. We identify regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia. This analytical result allows us to locate the transition in parameter space and highlights that the transition from regular to fibrillatory behaviour is a finite-size effect present in systems of any size. These clinically testable predictions might inform ablation therapies and arrhythmic risk assessment.

  4. Solution scanning as a key policy tool: identifying management interventions to help maintain and enhance regulating ecosystem services

    Directory of Open Access Journals (Sweden)

    William J. Sutherland

    2014-06-01

    Full Text Available The major task of policy makers and practitioners when confronted with a resource management problem is to decide on the potential solution(s to adopt from a range of available options. However, this process is unlikely to be successful and cost effective without access to an independently verified and comprehensive available list of options. There is currently burgeoning interest in ecosystem services and quantitative assessments of their importance and value. Recognition of the value of ecosystem services to human well-being represents an increasingly important argument for protecting and restoring the natural environment, alongside the moral and ethical justifications for conservation. As well as understanding the benefits of ecosystem services, it is also important to synthesize the practical interventions that are capable of maintaining and/or enhancing these services. Apart from pest regulation, pollination, and global climate regulation, this type of exercise has attracted relatively little attention. Through a systematic consultation exercise, we identify a candidate list of 296 possible interventions across the main regulating services of air quality regulation, climate regulation, water flow regulation, erosion regulation, water purification and waste treatment, disease regulation, pest regulation, pollination and natural hazard regulation. The range of interventions differs greatly between habitats and services depending upon the ease of manipulation and the level of research intensity. Some interventions have the potential to deliver benefits across a range of regulating services, especially those that reduce soil loss and maintain forest cover. Synthesis and applications: Solution scanning is important for questioning existing knowledge and identifying the range of options available to researchers and practitioners, as well as serving as the necessary basis for assessing cost effectiveness and guiding implementation strategies. We

  5. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma.

    Science.gov (United States)

    Kannan, Kasthuri; Inagaki, Akiko; Silber, Joachim; Gorovets, Daniel; Zhang, Jianan; Kastenhuber, Edward R; Heguy, Adriana; Petrini, John H; Chan, Timothy A; Huse, Jason T

    2012-10-01

    The molecular foundations of lower-grade gliomas (LGGs)-astrocytoma, oligodendroglioma, and oligoastrocytoma-remain less well characterized than those of their fully malignant counterpart, glioblastoma. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) likely represent initiating pathogenic events. However, while IDH mutations appear to dramatically alter cellular epigenomic landscapes, definitive downstream transformative mechanisms have not been characterized. It remains likely, therefore, that additional genomic abnormalities collaborate with IDH mutation to drive oncogenesis in LGG. We performed whole exome sequencing in 4 LGGs, followed by focused resequencing in an additional 28, and found a high incidence of mutations in the ATRX gene (α thalassemia/mental retardation syndrome X-linked). ATRX forms a core component of a chromatin remodeling complex active in telomere biology. Mutations in ATRX have been identified in multiple tumor types and appear to cause alternative lengthening of telomeres (ALT), a presumed precursor to genomic instability. In our samples, ATRX mutation was entirely restricted to IDH-mutant tumors, closely correlated with TP53 mutation and astrocytic differentiation, and mutually exclusive with 1p/19q codeletion, the molecular hallmark of oligodendroglioma. Moreover, ATRX mutation was highly enriched in tumors of so-called early progenitor-like transcriptional subclass (~85%), which our prior work has linked to specific cells of origin in the forebrain subventricular zone. Finally, ATRX mutation correlated with ALT, providing a mechanistic link to genomic instability. In summary, our findings both identify ATRX mutation as a defining molecular determinant for a large subset of IDH-mutant gliomas and have direct implications on pathogenic mechanisms across the wide spectrum of LGGs.

  6. Identifiability of Gaussian Structural Equation Models with Same Error Variances

    CERN Document Server

    Peters, Jonas

    2012-01-01

    We consider structural equation models (SEMs) in which variables can be written as a function of their parents and noise terms (the latter are assumed to be jointly independent). Corresponding to each SEM, there is a directed acyclic graph (DAG) G_0 describing the relationships between the variables. In Gaussian SEMs with linear functions, the graph can be identified from the joint distribution only up to Markov equivalence classes (assuming faithfulness). It has been shown, however, that this constitutes an exceptional case. In the case of linear functions and non-Gaussian noise, the DAG becomes identifiable. Apart from few exceptions the same is true for non-linear functions and arbitrarily distributed additive noise. In this work, we prove identifiability for a third modification: if we require all noise variables to have the same variances, again, the DAG can be recovered from the joint Gaussian distribution. Our result can be applied to the problem of causal inference. If the data follow a Gaussian SEM w...

  7. How to identify the key factors that affect driver perception of accident risk. A comparison between Italian and Spanish driver behavior.

    Science.gov (United States)

    de Oña, Juan; de Oña, Rocio; Eboli, Laura; Forciniti, Carmen; Mazzulla, Gabriella

    2014-12-01

    Road crashes can be caused by different factors, including infrastructure, vehicles, and human variables. Many research studies have focused solely on identifying the key factors that cause road crashes. From these studies, it emerged that human factors have the most relevant impact on accident severity. More specifically, accident severity depends on several factors related directly to the driver, i.e., driving experience, driver's socio-economic characteristics, and driving behavior and attitudes. In this paper, we investigate driver behaviors and attitudes while driving and specifically focus on different methods for identifying the factors that most affect the driver's perception of accident risk. To this end, we designed and conducted a survey in two different European contexts: the city of Cosenza, which is located in the south of Italy, and the city of Granada, which is located in the south of Spain. Samples of drivers were contacted for their opinions on certain aspects of driving rules and attitudes while driving, and different types of questions were addressed to the drivers to assess their judgments of these aspects. Consequently, different methods of data analysis were applied to determine the aspects that heavily influence driver perception of accident risk. An experiment based on the stated preferences (SP) was carried out with the drivers, and the SP data were analyzed using an ordered probit (OP) model. Interesting findings emerged from different analyses of the data and from the comparisons among the data collected in the two different territorial contexts. We found that both Italian and Spanish drivers consider driving in an altered psychophysical state and violating the overtaking rules to be the most risky behaviors.

  8. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions

    Directory of Open Access Journals (Sweden)

    Laura eGomez-Valero

    2011-10-01

    Full Text Available Although best known for its ability to cause severe pneumonia in people whose immune defenses are weakened, Legionella pneumophila and Legionella longbeachae are two species of a large genus of bacteria that are ubiquitous in nature, where they parasitize protozoa. Adaptation to the host environment and exploitation of host cell functions are critical for the success of these intracellular pathogens. The establishment and publication of the complete genome sequences of L. pneumophila and L. longbeachae isolates paved the way for major breakthroughs in understanding the biology of these organisms. In this review we present the knowledge gained from the analyses and comparison of the complete genome sequences of different L. pneumophila and L. longbeachae strains. Emphasis is given on putative virulence and Legionella life cycle related functions, such as the identification of an extended array of eukaryotic-like proteins, many of which have been shown to modulate host cell functions to the pathogen's advantage. Surprisingly, many of the eukaryotic domain proteins identified in L. pneumophila as well as many substrates of the Dot/Icm type IV secretion system essential for intracellular replication are different between these two species, although they cause the same disease. Finally, evolutionary aspects regarding the eukaryotic like proteins in Legionella are discussed.

  9. Identifying and preventing medical errors in patients with limited English proficiency: key findings and tools for the field.

    Science.gov (United States)

    Wasserman, Melanie; Renfrew, Megan R; Green, Alexander R; Lopez, Lenny; Tan-McGrory, Aswita; Brach, Cindy; Betancourt, Joseph R

    2014-01-01

    Since the 1999 Institute of Medicine (IOM) report To Err is Human, progress has been made in patient safety, but few efforts have focused on safety in patients with limited English proficiency (LEP). This article describes the development, content, and testing of two new evidence-based Agency for Healthcare Research and Quality (AHRQ) tools for LEP patient safety. In the content development phase, a comprehensive mixed-methods approach was used to identify common causes of errors for LEP patients, high-risk scenarios, and evidence-based strategies to address them. Based on our findings, Improving Patient Safety Systems for Limited English Proficient Patients: A Guide for Hospitals contains recommendations to improve detection and prevention of medical errors across diverse populations, and TeamSTEPPS Enhancing Safety for Patients with Limited English Proficiency Module trains staff to improve safety through team communication and incorporating interpreters in the care process. The Hospital Guide was validated with leaders in quality and safety at diverse hospitals, and the TeamSTEPPS LEP module was field-tested in varied settings within three hospitals. Both tools were found to be implementable, acceptable to their audiences, and conducive to learning. Further research on the impact of the combined use of the guide and module would shed light on their value as a multifaceted intervention.

  10. Stepwise organization of the β-structure identifies key regions essential for the propagation and cytotoxicity of insulin amyloid fibrils.

    Science.gov (United States)

    Chatani, Eri; Imamura, Hiroshi; Yamamoto, Naoki; Kato, Minoru

    2014-04-11

    Amyloid fibrils are supramolecular assemblies, the deposition of which is associated with many serious diseases including Alzheimer, prion, and Huntington diseases. Several smaller aggregates such as oligomers and protofibrils have been proposed to play a role in early stages of the fibrillation process; however, little is known about how these species contribute to the formation of mature amyloid fibrils with a rigid cross-β structure. Here, we identified a new pathway for the formation of insulin amyloid fibrils at a high concentration of salt in which mature fibrils were formed in a stepwise manner via a prefibrillar intermediate: minute prefibrillar species initially accumulated, followed by the subsequent formation of thicker amyloid fibrils. Fourier transform infrared spectra suggested the sequential formation of two types of β-sheets with different strength hydrogen bonds, one of which was developed concomitantly with the mutual assembly of the prefibrillar intermediate to form mature fibrils. Interestingly, fibril propagation and cellular toxicity appeared only after the later step of structural organization, and a comparison of β-sheet regions between the prefibrillar intermediate and mature fibrils using proteolysis led to the proposal of specific regions essential for manifestation of these properties.

  11. Functional analysis of a zebrafish myd88 mutant identifies key transcriptional components of the innate immune system

    Directory of Open Access Journals (Sweden)

    Michiel van der Vaart

    2013-05-01

    Toll-like receptors (TLRs are an important class of pattern recognition receptors (PRRs that recognize microbial and danger signals. Their downstream signaling upon ligand binding is vital for initiation of the innate immune response. In human and mammalian models, myeloid differentiation factor 88 (MYD88 is known for its central role as an adaptor molecule in interleukin 1 receptor (IL-1R and TLR signaling. The zebrafish is increasingly used as a complementary model system for disease research and drug screening. Here, we describe a zebrafish line with a truncated version of MyD88 as the first zebrafish mutant for a TLR signaling component. We show that this immune-compromised mutant has a lower survival rate under standard rearing conditions and is more susceptible to challenge with the acute bacterial pathogens Edwardsiella tarda and Salmonella typhimurium. Microarray and quantitative PCR analysis revealed that expression of genes for transcription factors central to innate immunity (including NF-ĸB and AP-1 and the pro-inflammatory cytokine Il1b, is dependent on MyD88 signaling during these bacterial infections. Nevertheless, expression of immune genes independent of MyD88 in the myd88 mutant line was sufficient to limit growth of an attenuated S. typhimurium strain. In the case of infection with the chronic bacterial pathogen Mycobacterium marinum, we show that MyD88 signaling has an important protective role during early pathogenesis. During mycobacterial infection, the myd88 mutant shows accelerated formation of granuloma-like aggregates and increased bacterial burden, with associated lower induction of genes central to innate immunity. This zebrafish myd88 mutant will be a valuable tool for further study of the role of IL1R and TLR signaling in the innate immunity processes underlying infectious diseases, inflammatory disorders and cancer.

  12. Statistical study to identify the key factors governing ground water recharge in the watersheds of the arid Central Asia.

    Science.gov (United States)

    Zhu, Binq-Qi; Wang, Yue-Ling

    2016-01-01

    Understanding the source and recharge of ground waters is of great significance to our knowledge in hydrological cycles in arid environments over the world. Northern Xinjiang in northwestern China is a significant repository of information relating to the hydrological evolution and climatic changes in central Asia. In this study, two multivariate statistical techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to assess the ground water recharge and its governing factors, with the principal idea of exploring the above techniques to utilize all available hydrogeochemical variables in the quality assessment, which are not considered in the conventional techniques like Stiff and Piper diagrams. Q-mode HCA and R-mode PCA were combined to partition the water samples into seven major water clusters (C1-C7) and three principal components (PC1-PC3, PC1 salinity, PC2 hydroclimate, PC3 contaminant). The water samples C1 + C4 were classified as recharge area waters (Ca-HCO3 water), C2 + C3 as transitional zone waters (Ca-Mg-HCO3-SO4 water), and C5 + C6 + C7 as discharge area waters (Na-SO4 water). Based on the Q-mode PCA scores, three groups of geochemical processes influencing recharge regimes were identified: geogenic (i.e., caused by natural geochemical processes), geomorphoclimatic (caused by topography and climate), and anthropogenic (caused by ground water contamination). It is proposed that differences in recharge mechanism and ground water evolution, and possible bedrock composition difference, are responsible for the chemical genesis of these waters. These will continue to influence the geochemistry of the northern Xinjiang drainage system for a long time due to its steady tectonics and arid climate. This study proved that the chemistry differentiation of ground water can effectively support the identification of ground water recharge and evolution patterns.

  13. Identifying Spatially Variable Sensitivity of Model Predictions and Calibrations

    Science.gov (United States)

    McKenna, S. A.; Hart, D. B.

    2005-12-01

    Stochastic inverse modeling provides an ensemble of stochastic property fields, each calibrated to measured steady-state and transient head data. These calibrated fields are used as input for predictions of other processes (e.g., contaminant transport, advective travel time). Use of the entire ensemble of fields transfers spatial uncertainty in hydraulic properties to uncertainty in the predicted performance measures. A sampling-based sensitivity coefficient is proposed to determine the sensitivity of the performance measures to the uncertain values of hydraulic properties at every cell in the model domain. The basis of this sensitivity coefficient is the Spearman rank correlation coefficient. Sampling-based sensitivity coefficients are demonstrated using a recent set of transmissivity (T) fields created through a stochastic inverse calibration process for the Culebra dolomite in the vicinity of the WIPP site in southeastern New Mexico. The stochastic inverse models were created using a unique approach to condition a geologically-based conceptual model of T to measured T values via a multiGaussian residual field. This field is calibrated to both steady-state and transient head data collected over an 11 year period. Maps of these sensitivity coefficients provide a means of identifying the locations in the study area to which both the value of the model calibration objective function and the predicted travel times to a regulatory boundary are most sensitive to the T and head values. These locations can be targeted for deployment of additional long-term monitoring resources. Comparison of areas where the calibration objective function and the travel time have high sensitivity shows that these are not necessarily coincident with regions of high uncertainty. The sampling-based sensitivity coefficients are compared to analytically derived sensitivity coefficients at the 99 pilot point locations. Results of the sensitivity mapping exercise are being used in combination

  14. Data publication and dissemination of interactive keys under the open access model

    Science.gov (United States)

    The concepts of publication, citation and dissemination of interactive keys and other online keys are discussed and illustrated by a sample paper published in the present issue (doi: 10.3897/zookeys.21.271). The present model is based on previous experience with several existing examples of publishi...

  15. Simple Model for Identifying Critical Regions in Atrial Fibrillation

    Science.gov (United States)

    Peters, Nicholas S.

    2015-01-01

    Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment. PMID:25635565

  16. An analysis of offshore wind farm SCADA measurements to identify key parameters influencing the magnitude of wake effects

    Science.gov (United States)

    Mittelmeier, N.; Blodau, T.; Steinfeld, G.; Rott, A.; Kühn, M.

    2016-09-01

    Atmospheric conditions have a clear influence on wake effects. Stability classification is usually based on wind speed, turbulence intensity, shear and temperature gradients measured partly at met masts, buoys or LiDARs. The objective of this paper is to find a classification for stability based on wind turbine Supervisory Control and Data Acquisition (SCADA) measurements in order to fit engineering wake models better to the current ambient conditions. Two offshore wind farms with met masts have been used to establish a correlation between met mast stability classification and new aggregated statistical signals based on multiple measurement devices. The significance of these new signals on power production is demonstrated for two wind farms with met masts and validated against data from one further wind farm without a met mast. We found a good correlation between the standard deviation of active power divided by the average power of wind turbines in free flow with the ambient turbulence intensity when the wind turbines were operating in partial load.

  17. Key landscape and biotic indicators of watersheds sensitivity to forest disturbance identified using remote sensing and historical hydrography data

    Science.gov (United States)

    Buma, Brian; Livneh, Ben

    2017-07-01

    Water is one of the most critical resources derived from natural systems. While it has long been recognized that forest disturbances like fire influence watershed streamflow characteristics, individual studies have reported conflicting results with some showing streamflow increases post-disturbance and others decreases, while other watersheds are insensitive to even large disturbance events. Characterizing the differences between sensitive (e.g. where streamflow does change post-disturbance) and insensitive watersheds is crucial to anticipating response to future disturbance events. Here, we report on an analysis of a national-scale, gaged watershed database together with high-resolution forest mortality imagery. A simple watershed response model was developed based on the runoff ratio for watersheds (n = 73) prior to a major disturbance, detrended for variation in precipitation inputs. Post-disturbance deviations from the expected water yield and streamflow timing from expected (based on observed precipitation) were then analyzed relative to the abiotic and biotic characteristics of the individual watershed and observed extent of forest mortality. The extent of the disturbance was significantly related to change in post-disturbance water yield (p water yield. Highly disturbed, arid watersheds with low soil: water contact time are the most likely to see increases, with the magnitude positively correlated with the extent of disturbance. Watersheds dominated by deciduous forest with low bulk density soils typically show reduced yield post-disturbance. Post-disturbance streamflow timing change was associated with climate, forest type, and soil. Snowy coniferous watersheds were generally insensitive to disturbance, whereas finely textured soils with rapid runoff were sensitive. This is the first national scale investigation of streamflow post-disturbance using fused gage and remotely sensed data at high resolution, and gives important insights that can be used to

  18. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    Science.gov (United States)

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  19. Sleeping Beauty mouse models identify candidate genes involved in gliomagenesis.

    Directory of Open Access Journals (Sweden)

    Irina Vyazunova

    Full Text Available Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma.

  20. Sleeping Beauty Mouse Models Identify Candidate Genes Involved in Gliomagenesis

    Science.gov (United States)

    Vyazunova, Irina; Maklakova, Vilena I.; Berman, Samuel; De, Ishani; Steffen, Megan D.; Hong, Won; Lincoln, Hayley; Morrissy, A. Sorana; Taylor, Michael D.; Akagi, Keiko; Brennan, Cameron W.; Rodriguez, Fausto J.; Collier, Lara S.

    2014-01-01

    Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma. PMID:25423036

  1. How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia

    OpenAIRE

    Freeman, Daniel; Dunn, Graham; Murray, Robin M.; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M.; Harrison, Paul J

    2014-01-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis—∆9-tetrahydrocannabinol (THC)—causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled...

  2. Rate Regions of Secret Key Sharing in a New Source Model

    CERN Document Server

    Salimi, Somayeh; Aref, Mohammad Reza

    2010-01-01

    A source model for secret key generation between terminals is considered. Two users, namely users 1 and 2, at one side communicate with another user, namely user 3, at the other side via a public channel where three users can observe i.i.d. outputs of correlated sources. Each of users 1 and 2 intends to share a secret key with user 3 where user 1 acts as a wiretapper for user 2 and vice versa. In this model, two situations are considered: communication from users 1 and 2 to user 3 (the forward key strategy) and from user 3 to users 1 and 2 (the backward key strategy). In both situations, the goal is sharing a secret key between user 1 and user 3 while leaking no effective information about that key to user 2, and simultaneously, sharing another secret key between user 2 and user 3 while leaking no effective information about the latter key to user 1. This model is motivated by wireless communications when considering user 3 as a base station and users 1 and 2 as network users. In this paper, for both the forw...

  3. A step towards considering the spatial heterogeneity of urban key features in urban hydrology flood modelling

    Science.gov (United States)

    Leandro, J.; Schumann, A.; Pfister, A.

    2016-04-01

    Some of the major challenges in modelling rainfall-runoff in urbanised areas are the complex interaction between the sewer system and the overland surface, and the spatial heterogeneity of the urban key features. The former requires the sewer network and the system of surface flow paths to be solved simultaneously. The latter is still an unresolved issue because the heterogeneity of runoff formation requires high detailed information and includes a large variety of feature specific rainfall-runoff dynamics. This paper discloses a methodology for considering the variability of building types and the spatial heterogeneity of land surfaces. The former is achieved by developing a specific conceptual rainfall-runoff model and the latter by defining a fully distributed approach for infiltration processes in urban areas with limited storage capacity dependent on OpenStreetMaps (OSM). The model complexity is increased stepwise by adding components to an existing 2D overland flow model. The different steps are defined as modelling levels. The methodology is applied in a German case study. Results highlight that: (a) spatial heterogeneity of urban features has a medium to high impact on the estimated overland flood-depths, (b) the addition of multiple urban features have a higher cumulative effect due to the dynamic effects simulated by the model, (c) connecting the runoff from buildings to the sewer contributes to the non-linear effects observed on the overland flood-depths, and (d) OSM data is useful in identifying pounding areas (for which infiltration plays a decisive role) and permeable natural surface flow paths (which delay the flood propagation).

  4. Identifying an appropriate measurement modeling approach for the Mini-Mental State Examination.

    Science.gov (United States)

    Rubright, Jonathan D; Nandakumar, Ratna; Karlawish, Jason

    2016-02-01

    The Mini-Mental State Examination (MMSE) is a 30-item, dichotomously scored test of general cognition. A number of benefits could be gained by modeling the MMSE in an item response theory (IRT) framework, as opposed to the currently used classical additive approach. However, the test, which is built from groups of items related to separate cognitive subdomains, may violate a key assumption of IRT: local item independence. This study aimed to identify the most appropriate measurement model for the MMSE: a unidimensional IRT model, a testlet response theory model, or a bifactor model. Local dependence analysis using nationally representative data showed a meaningful violation of the local item independence assumption, indicating multidimensionality. In addition, the testlet and bifactor models displayed superior fit indices over a unidimensional IRT model. Statistical comparisons showed that the bifactor model fit MMSE respondent data significantly better than the other models considered. These results suggest that application of a traditional unidimensional IRT model is inappropriate in this context. Instead, a bifactor model is suggested for future modeling of MMSE data as it more accurately represents the multidimensional nature of the scale. (PsycINFO Database Record

  5. Method of Identifying Key Quality Characteristics in Multistage Manufacturing Process Based on PLSR%基于 PLSR 的多级制造过程关键质量特性识别方法

    Institute of Scientific and Technical Information of China (English)

    王宁; 徐济超; 杨剑锋

    2013-01-01

    To solve the multicollinearity problem between quality characteristics in identifying the key quality characteristics of multistage manufacturing process , the partial least squares regression ( PLSR) method is intro-duced to model and analyze the key quality characteristics identifying model .Firstly, the state space model is applied to model the key quality characteristics identifying model multistage manufacturing process .Then using the PLSR method to solve the multicollinearity problem , we make a model analyse and identify the key quality characteristics.Lastly, the cigarette production process is taken as an example to introduce the method applica -tion.The result shows that this method not only could identify the key quality characteristics in multistage manu-facturing process , but also establish the model of output quality effecting of all levels on the final product quality and their quality characteristics relationship , which reflect the structure of the multistage manufacturing process and causal relationship between quality characteristics at all process levels , providing the basis for quality analysis and control in multistage manufacturing process .%为解决多级制造过程关键质量特性识别中多质量特性之间的相关性问题,将偏最小二乘回归方法( Par-tial Least Squares Regression , PLSR)引入模型构建与分析中。首先应用状态空间方法建立多级制造过程关键质量特性识别模型,进而利用PLSR方法解决质量特性间的多重共线性问题并进行模型分析,识别关键质量特性,最后以卷烟生产过程为例介绍了该方法的应用。实例表明,该方法不仅可以有效识别多级制造过程关键质量特性,而且能够建立各级过程的输出质量对最终产品质量的影响及其质量特性之间相互关系的模型,反映多级生产过程的结构特征和各级过程质量特性之间的因果关系,为多级制造过程质量分析与控制提供依据。

  6. Modeling secondary accidents identified by traffic shock waves.

    Science.gov (United States)

    Junhua, Wang; Boya, Liu; Lanfang, Zhang; Ragland, David R

    2016-02-01

    The high potential for occurrence and the negative consequences of secondary accidents make them an issue of great concern affecting freeway safety. Using accident records from a three-year period together with California interstate freeway loop data, a dynamic method for more accurate classification based on the traffic shock wave detecting method was used to identify secondary accidents. Spatio-temporal gaps between the primary and secondary accident were proven be fit via a mixture of Weibull and normal distribution. A logistic regression model was developed to investigate major factors contributing to secondary accident occurrence. Traffic shock wave speed and volume at the occurrence of a primary accident were explicitly considered in the model, as a secondary accident is defined as an accident that occurs within the spatio-temporal impact scope of the primary accident. Results show that the shock waves originating in the wake of a primary accident have a more significant impact on the likelihood of a secondary accident occurrence than the effects of traffic volume. Primary accidents with long durations can significantly increase the possibility of secondary accidents. Unsafe speed and weather are other factors contributing to secondary crash occurrence. It is strongly suggested that when police or rescue personnel arrive at the scene of an accident, they should not suddenly block, decrease, or unblock the traffic flow, but instead endeavor to control traffic in a smooth and controlled manner. Also it is important to reduce accident processing time to reduce the risk of secondary accident. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 基于网页坐标系的主题信息块判定研究%Exploring the Identifying Key Information with Coordinate System in Webpage

    Institute of Scientific and Technical Information of China (English)

    张力

    2014-01-01

    Applying the theory of VIPS in the coordinate system of Webpage,the way of identifying key information in Webpage is developed.The method focuses on judging the visual focus of people in de-signing or browsing the Webpage,for identifying key information within distributing nine-square grid.At last,with several dissection ratios,News websites are discussed that spatial level of information block and extracting key information block are linked in web pages.%在网页坐标系中运用 VIPS(Vision-based page segmentation)理论,对网页中信息块的重要性进行判定。该方法利用网页创建过程中的设计习惯和人类浏览信息过程中的视觉焦点判定,按九宫格划分页面区域分布并在此基础上识别主题信息,论文最后选取新闻类型网站网页,按不同页面分割比例检测了网页信息块空间层次和主题信息块提取间的关系。

  8. Procedure for identifying models for the heat dynamics of buildings

    DEFF Research Database (Denmark)

    Bacher, Peder; Madsen, Henrik

    This report describes a new method for obtaining detailed information about the heat dynamics of a building using frequent reading of the heat consumption. Such a procedure is considered to be of uttermost importance as a key procedure for using readings from smart meters, which is expected...... to be installed in almost all buildings in the coming years....

  9. Simple Empirical Model for Identifying Rheological Properties of Soft Biological Tissues

    CERN Document Server

    Kobayashi, Yo; Miyashita, Tomoyuki; Fujie, Masakatsu G

    2015-01-01

    Understanding the rheological properties of soft biological tissue is a key issue for mechanical systems used in the healthcare field. We propose a simple empirical model using Fractional Dynamics and Exponential Nonlinearity (FDEN) to identify the rheological properties of soft biological tissue. The model is derived from detailed material measurements using samples isolated from porcine liver. We conducted dynamic viscoelastic and creep tests on liver samples using a rheometer. The experimental results indicated that biological tissue has specific properties: i) power law increases in storage elastic modulus and loss elastic modulus with the same slope; ii) power law gain decrease and constant phase delay in the frequency domain over two decades; iii) log-log scale linearity between time and strain relationships under constant force; and iv) linear and log scale linearity between strain and stress relationships. Our simple FDEN model uses only three dependent parameters and represents the specific propertie...

  10. A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity.

    Science.gov (United States)

    Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

    2016-05-01

    The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition.

  11. Electronic Service Architecture Model Assessment of Conformity to Cloud Computing Key Features

    OpenAIRE

    Stipravietis, P; Žeiris, E; Ziema, M

    2013-01-01

    The research examines electronic service execution possibilities in cloud computing environment and the key features of cloud computing. It also offers a method which allows quantitatively assess the conformity of existing e-service architecture model to cloud computing key features.The method allows evaluating the amount of necessary transformations and their efficiency. The offered solution is verified using the business process administered by Motor Insurance Bureau...

  12. Description of male, pupa and larva of Simulium (Asiosimulium) wanchaii (Diptera: Simuliidae) from Thailand, with keys to identify four species of the subgenus Asiosimulium.

    Science.gov (United States)

    Srisuka, W; Takaoka, H; Saeung, A

    2015-09-01

    The male, pupa and mature larva of Simulium (Asiosimulium) wanchaii Takaoka & Choochote, one of the four species of the small Oriental black fly subgenus Asiosimulium, are described for the first time based on samples collected from Thailand. The male S. (A.) wanchaii is characterized based on the enlarged hind basitarsus and the ventral plate which is much wider than long. The pupa and larva are characterized by the gill with 19 filaments and the deep postgenal cleft, respectively. Keys are provided to identify all the four species of the subgenus Asiosimulium for females, males, pupae and mature larvae.

  13. Identifying western yellow-billed cuckoo breeding habitat with a dual modelling approach

    Science.gov (United States)

    Johnson, Matthew J.; Hatten, James R.; Holmes, Jennifer A.; Shafroth, Patrick B.

    2017-01-01

    The western population of the yellow-billed cuckoo (Coccyzus americanus) was recently listed as threatened under the federal Endangered Species Act. Yellow-billed cuckoo conservation efforts require the identification of features and area requirements associated with high quality, riparian forest habitat at spatial scales that range from nest microhabitat to landscape, as well as lower-suitability areas that can be enhanced or restored. Spatially explicit models inform conservation efforts by increasing ecological understanding of a target species, especially at landscape scales. Previous yellow-billed cuckoo modelling efforts derived plant-community maps from aerial photography, an expensive and oftentimes inconsistent approach. Satellite models can remotely map vegetation features (e.g., vegetation density, heterogeneity in vegetation density or structure) across large areas with near perfect repeatability, but they usually cannot identify plant communities. We used aerial photos and satellite imagery, and a hierarchical spatial scale approach, to identify yellow-billed cuckoo breeding habitat along the Lower Colorado River and its tributaries. Aerial-photo and satellite models identified several key features associated with yellow-billed cuckoo breeding locations: (1) a 4.5 ha core area of dense cottonwood-willow vegetation, (2) a large native, heterogeneously dense forest (72 ha) around the core area, and (3) moderately rough topography. The odds of yellow-billed cuckoo occurrence decreased rapidly as the amount of tamarisk cover increased or when cottonwood-willow vegetation was limited. We achieved model accuracies of 75–80% in the project area the following year after updating the imagery and location data. The two model types had very similar probability maps, largely predicting the same areas as high quality habitat. While each model provided unique information, a dual-modelling approach provided a more complete picture of yellow-billed cuckoo habitat

  14. The building blocks of a 'Liveable Neighbourhood': Identifying the key performance indicators for walking of an operational planning policy in Perth, Western Australia.

    Science.gov (United States)

    Hooper, Paula; Knuiman, Matthew; Foster, Sarah; Giles-Corti, Billie

    2015-11-01

    Planning policy makers are requesting clearer guidance on the key design features required to build neighbourhoods that promote active living. Using a backwards stepwise elimination procedure (logistic regression with generalised estimating equations adjusting for demographic characteristics, self-selection factors, stage of construction and scale of development) this study identified specific design features (n=16) from an operational planning policy ("Liveable Neighbourhoods") that showed the strongest associations with walking behaviours (measured using the Neighbourhood Physical Activity Questionnaire). The interacting effects of design features on walking behaviours were also investigated. The urban design features identified were grouped into the "building blocks of a Liveable Neighbourhood", reflecting the scale, importance and sequencing of the design and implementation phases required to create walkable, pedestrian friendly developments.

  15. Passage Key Inlet, Florida; CMS Modeling and Borrow Site Impact Analysis

    Science.gov (United States)

    2016-06-01

    use of a nested Coastal Modeling System (CMS) model for Passage Key Inlet, which is one of the connections between the Gulf of Mexico and Tampa Bay...XIV-51 June 2016 2 Figure 1. Active USACE Jacksonville District (SAJ) projects in Pinellas, Manatee, and Sarasota Counties, FL. METHOD : The CMS...is a product of the Coastal Inlets Research Program (http://cirp.usace.army.mil) managed at ERDC. CMS is composed of two models, CMS-Flow (Buttolph

  16. Identifying errors in dust models from data assimilation.

    Science.gov (United States)

    Pope, R J; Marsham, J H; Knippertz, P; Brooks, M E; Roberts, A J

    2016-09-16

    Airborne mineral dust is an important component of the Earth system and is increasingly predicted prognostically in weather and climate models. The recent development of data assimilation for remotely sensed aerosol optical depths (AODs) into models offers a new opportunity to better understand the characteristics and sources of model error. Here we examine assimilation increments from Moderate Resolution Imaging Spectroradiometer AODs over northern Africa in the Met Office global forecast model. The model underpredicts (overpredicts) dust in light (strong) winds, consistent with (submesoscale) mesoscale processes lifting dust in reality but being missed by the model. Dust is overpredicted in the Sahara and underpredicted in the Sahel. Using observations of lighting and rain, we show that haboobs (cold pool outflows from moist convection) are an important dust source in reality but are badly handled by the model's convection scheme. The approach shows promise to serve as a useful framework for future model development.

  17. Key-Aspects of Scientific Modeling Exemplified by School Science Models: Some Units for Teaching Contextualized Scientific Methodology

    Science.gov (United States)

    Develaki, Maria

    2016-01-01

    Models and modeling are core elements of scientific methods and consequently also are of key importance for the conception and teaching of scientific methodology. The epistemology of models and its transfer and adaption to nature of science education are not, however, simple themes. We present some conceptual units in which school science models…

  18. The Sender-Excited Secret Key Agreement Model: Capacity and Error Exponents

    CERN Document Server

    Chou, Tzu-Han; Draper, Stark C

    2011-01-01

    We consider fundamental limits of the secret key generation problem when the sources are randomly excited by the sender and there is a noiseless public discussion channel. In many practical communication settings, the sources or channels may be influenced by some parties involved. Similar to recent works on probing capacity and channels with action-dependent states, our system model captures such a scenario. We derive single-letter expressions for the secret key capacity. Our coding strategy involves wiretap channel coding and a key generation scheme. We show that the secret key capacity is composed of both source- and channel-type randomness. By assuming that the eavesdropper receives a degraded version of the legitimate receiver's observation, we also obtain a capacity result that does not involve any auxiliary random variables, and thus it is amenable to numerical evaluation. By evaluating the capacity for several degraded channels, we show that there is a fundamental interplay between the portion of the s...

  19. Key Frame Extraction Using Unsupervised Clustering Based on a Statistical Model

    Institute of Scientific and Technical Information of China (English)

    YANG Shuping; LIN Xinggang

    2005-01-01

    This paper proposes a novel algorithm for extracting key frames to represent video shots. Regarding whether, or how well, a key frame represents a shot, different interpretations have been suggested. We develop our algorithm on the assumption that more important content may demand more attention and may last relatively more frames. Unsupervised clustering is used to divide the frames into clusters within a shot, and then a key frame is selected from each candidate cluster. To make the algorithm independent of video sequences, we employ a statistical model to calculate the clustering threshold. The proposed algorithm can capture the important yet salient content as the key frame. Its robustness and adaptability are validated by experiments with various kinds of video sequences.

  20. Data publication and dissemination of interactive keys under the open access model

    Directory of Open Access Journals (Sweden)

    Lyubomir Penev

    2009-09-01

    Full Text Available The concepts of publication, citation and dissemination of interactive keys and other online keys are discussed and illustrated by a sample paper published in the present issue (doi: 10.3897/zookeys.21.271. The present model is based on previous experience with several existing examples of publishing online keys. However, this model also suggests ways to publish, cite, preserve, disseminate and reuse the original data files to the benefit of the authors, future workers, and society in general. To be regarded as a ''formal scientific publication,'' an online key should satisfy the same criteria of peer review, registration, persistence, bibliographic description, etc., as conventional publications. Keys can be published in a form of either ''static'\\''dynamic'' publications. We define a ''static'' publication as a discrete unit of information preserved in a persistent and unchangeable way on the publisher’s Web site and/or on paper and consequently in conventional/electronic libraries and archives. This contrasts with the nature of the Internet, which allows and tends to encourage updating and improvement on a continuing basis. We call ''dynamic'' a publication of an interactive key on a Web site where its contents can be continuously updated. ''Dynamic'' publications meet some of the criteria of a ''formal scientific publication'' (identification, citation and location, while they lack other important features of it (persistence, archiving, indexing, science metric and citation metric services. Dynamic Web-based interactive keys may benefit from publishing the first version of their underlying datasets in a form of “formal scientific publication”. We define here the minimum set of data files to be published for several different platforms (Intkey, Lucid2, Lucid3, MX to ensure both (1 priority, identification, location and citation of the firstly published work and (2 future use and re-use of the keys.

  1. Password-only authenticated three-party key exchange with provable security in the standard model.

    Science.gov (United States)

    Nam, Junghyun; Choo, Kim-Kwang Raymond; Kim, Junghwan; Kang, Hyun-Kyu; Kim, Jinsoo; Paik, Juryon; Won, Dongho

    2014-01-01

    Protocols for password-only authenticated key exchange (PAKE) in the three-party setting allow two clients registered with the same authentication server to derive a common secret key from their individual password shared with the server. Existing three-party PAKE protocols were proven secure under the assumption of the existence of random oracles or in a model that does not consider insider attacks. Therefore, these protocols may turn out to be insecure when the random oracle is instantiated with a particular hash function or an insider attack is mounted against the partner client. The contribution of this paper is to present the first three-party PAKE protocol whose security is proven without any idealized assumptions in a model that captures insider attacks. The proof model we use is a variant of the indistinguishability-based model of Bellare, Pointcheval, and Rogaway (2000), which is one of the most widely accepted models for security analysis of password-based key exchange protocols. We demonstrated that our protocol achieves not only the typical indistinguishability-based security of session keys but also the password security against undetectable online dictionary attacks.

  2. Password-Only Authenticated Three-Party Key Exchange with Provable Security in the Standard Model

    Directory of Open Access Journals (Sweden)

    Junghyun Nam

    2014-01-01

    Full Text Available Protocols for password-only authenticated key exchange (PAKE in the three-party setting allow two clients registered with the same authentication server to derive a common secret key from their individual password shared with the server. Existing three-party PAKE protocols were proven secure under the assumption of the existence of random oracles or in a model that does not consider insider attacks. Therefore, these protocols may turn out to be insecure when the random oracle is instantiated with a particular hash function or an insider attack is mounted against the partner client. The contribution of this paper is to present the first three-party PAKE protocol whose security is proven without any idealized assumptions in a model that captures insider attacks. The proof model we use is a variant of the indistinguishability-based model of Bellare, Pointcheval, and Rogaway (2000, which is one of the most widely accepted models for security analysis of password-based key exchange protocols. We demonstrated that our protocol achieves not only the typical indistinguishability-based security of session keys but also the password security against undetectable online dictionary attacks.

  3. Modeling and analysis of PM2.5 generation for key factors identification in China

    Science.gov (United States)

    Xia, Dehong; Jiang, Binfan; Xie, Yulei

    2016-06-01

    Recently, the PM2.5 pollution in China has occurred frequently and caused widely concern. In order to identify the key factors for PM2.5 generation, the formation characteristics of PM2.5 would be revealed. A property of electric neutrality of PM2.5 was proposed under the least-energy principle and verified through electricity-charge calculation in this paper. It indicated that PM2.5 is formed by the effect of electromagnetic force, including the effect of ionic bond, hydrogen bond and polarization. According to the analysis of interactive forces among different chemical components, a simulation model is developed for describing the random process of PM2.5 generation. In addition, an orthogonal test with two levels and four factors has been designed and carried out through the proposed model. From the text analysis, PM2.5 would be looser and suspend longer in atmosphere due to Organic Compound (OC) existing (OC can reduce about 67% of PM2.5 density). Considering that NH4+ is the only cation in the main chemical components of PM2.5, it would be vital for anions (such as SO42- and NO3-) to aggregate together for facilitating PM2.5 growing. Therefore, in order to relieve PM2.5 pollution, control strategies for OC and NH4+ would be enhanced by government through improving the quality of oils and solvent products, decreasing the amount of nitrogenous fertilizer utilization, or changing the fertilizing environment from dry condition to wet condition.

  4. Avoiding and identifying errors in health technology assessment models: qualitative study and methodological review.

    Science.gov (United States)

    Chilcott, J; Tappenden, P; Rawdin, A; Johnson, M; Kaltenthaler, E; Paisley, S; Papaioannou, D; Shippam, A

    2010-05-01

    , stepping through skeleton models with experts, ensuring transparency in reporting, adopting standard housekeeping techniques, and ensuring that those parties involved in the model development process have sufficient and relevant training. Clarity and mutual understanding were identified as key issues. However, their current implementation is not framed within an overall strategy for structuring complex problems. Some of the questioning may have biased interviewees responses but as all interviewees were represented in the analysis no rebalancing of the report was deemed necessary. A potential weakness of the literature review was its focus on spreadsheet and program development rather than specifically on model development. It should also be noted that the identified literature concerning programming errors was very narrow despite broad searches being undertaken. Published definitions of overall model validity comprising conceptual model validation, verification of the computer model, and operational validity of the use of the model in addressing the real-world problem are consistent with the views expressed by the HTA community and are therefore recommended as the basis for further discussions of model credibility. Such discussions should focus on risks, including errors of implementation, errors in matters of judgement and violations. Discussions of modelling risks should reflect the potentially complex network of cognitive breakdowns that lead to errors in models and existing research on the cognitive basis of human error should be included in an examination of modelling errors. There is a need to develop a better understanding of the skills requirements for the development, operation and use of HTA models. Interaction between modeller and client in developing mutual understanding of a model establishes that model's significance and its warranty. This highlights that model credibility is the central concern of decision-makers using models so it is crucial that the

  5. Identifying anaerobic digestion models using simultaneous batch experiments

    Energy Technology Data Exchange (ETDEWEB)

    Flotats, X.; Palatsi, J.; Fernandez, B.; Colomer, M. A.; Illa, J.

    2009-07-01

    As in other wastewater treatment processes, anaerobic digestion models have become a valuable tool to increase the understanding of complex biodegradation processes, to teach and to communicate using a common language, to optimize design plants and operating strategies and for trying operators and process engineers. Models require accurate and significant parameter values for being useful. (Author) 2 refs.

  6. Modelling intelligence-led policing to identify its potential

    NARCIS (Netherlands)

    Hengst-Bruggeling, M. den; Graaf, H.A.L.M. de; Scheepstal, P.G.M. van

    2014-01-01

    lntelligence-led policing is a concept of policing that has been applied throughout the world. Despite some encouraging reports, the effect of intelligence-led policing is largely unknown. This paper presents a method with which it is possible to identify intelligence-led policing's potential to

  7. Modelling intelligence-led policing to identify its potential

    NARCIS (Netherlands)

    Hengst-Bruggeling, M. den; Graaf, H.A.L.M. de; Scheepstal, P.G.M. van

    2014-01-01

    lntelligence-led policing is a concept of policing that has been applied throughout the world. Despite some encouraging reports, the effect of intelligence-led policing is largely unknown. This paper presents a method with which it is possible to identify intelligence-led policing's potential to inc

  8. A new notion of soundness in bare public-key model

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yunlei; ZHU Hong

    2003-01-01

    A new notion of soundness in bare public-key (BPK) model is presented. This new notion just lies in between one-time soundness and sequential soundness and its reasonableness is justified in the context of resettable zero-knowledge when resettable zero-knowledge prover is implemented by smart card.

  9. Nine key principles to guide youth mental health: development of service models in New South Wales.

    Science.gov (United States)

    Howe, Deborah; Batchelor, Samantha; Coates, Dominiek; Cashman, Emma

    2014-05-01

    Historically, the Australian health system has failed to meet the needs of young people with mental health problems and mental illness. In 2006, New South Wales (NSW) Health allocated considerable funds to the reform agenda of mental health services in NSW to address this inadequacy. Children and Young People's Mental Health (CYPMH), a service that provides mental health care for young people aged 12-24 years, with moderate to severe mental health problems, was chosen to establish a prototype Youth Mental Health (YMH) Service Model for NSW. This paper describes nine key principles developed by CYPMH to guide the development of YMH Service Models in NSW. A literature review, numerous stakeholder consultations and consideration of clinical best practice were utilized to inform the development of the key principles. Subsequent to their development, the nine key principles were formally endorsed by the Mental Health Program Council to ensure consistency and monitor the progress of YMH services across NSW. As a result, between 2008 and 2012 YMH Services across NSW regularly reported on their activities against each of the nine key principles demonstrating how each principle was addressed within their service. The nine key principles provide mental health services a framework for how to reorient services to accommodate YMH and provide a high-quality model of care. [Corrections added on 29 November 2013, after first online publication: The last two sentences of the Results section have been replaced with "As a result, between 2008 and 2012 YMH Services across NSW regularly reported on their activities against each of the nine key principles demonstrating how each principle was addressed within their service."]. © 2013 Wiley Publishing Asia Pty Ltd.

  10. A Method to Identify Flight Obstacles on Digital Surface Model

    Institute of Scientific and Technical Information of China (English)

    ZHAO Min; LIN Xinggang; SUN Shouyu; WANG Youzhi

    2005-01-01

    In modern low-altitude terrain-following guidance, a constructing method of the digital surface model (DSM) is presented in the paper to reduce the threat to flying vehicles of tall surface features for safe flight. The relationship between an isolated obstacle size and the intervals of vertical- and cross-section in the DSM model is established. The definition and classification of isolated obstacles are proposed, and a method for determining such isolated obstacles in the DSM model is given. The simulation of a typical urban district shows that when the vertical- and cross-section DSM intervals are between 3 m and 25 m, the threat to terrain-following flight at low-altitude is reduced greatly, and the amount of data required by the DSM model for monitoring in real time a flying vehicle is also smaller. Experiments show that the optimal results are for an interval of 12.5 m in the vertical- and cross-sections in the DSM model, with a 1:10 000 DSM scale grade.

  11. Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role in progression and metastasis of colorectal cancer.

    Science.gov (United States)

    Zheng, Ping; Liu, Yong-Xia; Chen, Lin; Liu, Xun-Hua; Xiao, Zheng-Quan; Zhao, Liang; Li, Guang-Qiu; Zhou, Jun; Ding, Yan-Qing; Li, Jian-Ming

    2010-10-01

    To better understand the role of PRL-3 in progression and metastasis of colorectal cancer (CRC), we searched for PRL-3 associated proteins using proteomic methods. We identified 39 PRL-3 associated proteins based on proteomic strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines and CRC tissues indicated that PRL-3 could interact with stathmin. And, both stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells. Moreover, gain-of-function and loss-of-function analyses revealed that stathmin promoted proliferation, cell adhesion, and migration of human CRC cells. Immunohistochemical analysis of 149 colorectal tumor samples showed that overexpression of stathmin was strongly correlated with tumor differentiation (P = 0.035), tumor invasion (P = 0.024), lymph node status (P PRL-3 associated proteins for the first time. The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC.

  12. Using the Theory of Planned Behavior to identify key beliefs underlying chlamydia testing intentions in a sample of young people living in deprived areas.

    Science.gov (United States)

    Booth, Amy R; Norman, Paul; Harris, Peter R; Goyder, Elizabeth

    2015-09-01

    The Theory of Planned Behavior was used to identify the key behavioural, normative and control beliefs underlying intentions to test regularly for chlamydia among young people living in socially and economically deprived areas - a high-risk group for infection. Participants (N = 278, 53% male; mean age 17 years) were recruited from a vocational college situated in an area in the most deprived national quintile (England). Participants completed measures of behavioural, normative and control beliefs, plus intention to test regularly for chlamydia. The behavioural, normative and control beliefs most strongly correlated with intentions to test regularly for chlamydia were beliefs about stopping the spread of infection, partners' behaviour and the availability of testing. These beliefs represent potential targets for interventions to increase chlamydia testing among young people living in deprived areas.

  13. Diurnal Cycle of the North American Monsoon in a Mesoscale Model Simulation: Evolution of Key Parameters in Relation to Precipitation

    Directory of Open Access Journals (Sweden)

    Weizhong Zheng

    2011-04-01

    Full Text Available The diurnal cycle of the North American monsoon is analyzed based on the output from a mesoscale model simulation. Statistically significant diurnal cycle in precipitation is identified, with heavy precipitation—essentially convective—dominating in local afternoons. Temporal evolution of key parameters in relation to precipitation is investigated, based on which a sequence of the dynamic/thermodynamic processes underlying precipitation development is proposed. Particularly, the afternoon peak in precipitation is found preceded by enhanced static instability and low-level convergence.

  14. Content-Based Search on a Database of Geometric Models: Identifying Objects of Similar Shape

    Energy Technology Data Exchange (ETDEWEB)

    XAVIER, PATRICK G.; HENRY, TYSON R.; LAFARGE, ROBERT A.; MEIRANS, LILITA; RAY, LAWRENCE P.

    2001-11-01

    The Geometric Search Engine is a software system for storing and searching a database of geometric models. The database maybe searched for modeled objects similar in shape to a target model supplied by the user. The database models are generally from CAD models while the target model may be either a CAD model or a model generated from range data collected from a physical object. This document describes key generation, database layout, and search of the database.

  15. AIDS policy modeling for the 21st century: an overview of key issues.

    Science.gov (United States)

    Rauner, M S; Brandeau, M L

    2001-09-01

    Decisions about HIV prevention and treatment programs are based on factors such as program costs and health benefits, social and ethical issues, and political considerations. AIDS policy models--that is, models that evaluate the monetary and non-monetary consequences of decisions about HIV/AIDS interventions--can play a role in helping policy makers make better decisions. This paper provides an overview of the key issues related to developing useful AIDS policy models. We highlight issues of importance for researchers in the field of AIDS policy modeling as well as for policy makers. These include geographic area, setting, target groups, interventions, affordability and effectiveness of interventions, type and time horizon of policy model, and type of economic analysis. This paper is not intended to be an exhaustive review of the AIDS policy modeling literature, although many papers from the literature are discussed as examples; rather, we aim to convey the composition, achievements, and challenges of AIDS policy modeling.

  16. An ecohydraulic model to identify and monitor moapa dace habitat

    Science.gov (United States)

    Hatten, James R.; Batt, Thomas R.; Scoppettone, Gayton G.; Dixon, Christopher J.

    2013-01-01

    Moapa dace (Moapa coriacea) is a critically endangered thermophilic minnow native to the Muddy River ecosystem in southeastern Nevada, USA. Restricted to temperatures between 26.0 and 32.0°C, these fish are constrained to the upper two km of the Muddy River and several small tributaries fed by warm springs. Habitat alterations, nonnative species invasion, and water withdrawals during the 20th century resulted in a drastic decline in the dace population and in 1979 the Moapa Valley National Wildlife Refuge (Refuge) was created to protect them. The goal of our study was to determine the potential effects of reduced surface flows that might result from groundwater pumping or water diversions on Moapa dace habitat inside the Refuge. We accomplished our goal in several steps. First, we conducted snorkel surveys to determine the locations of Moapa dace on three warm-spring tributaries of the Muddy River. Second, we conducted hydraulic simulations over a range of flows with a two-dimensional hydrodynamic model. Third, we developed a set of Moapa dace habitat models with logistic regression and a geographic information system. Fourth, we estimated Moapa dace habitat over a range of flows (plus or minus 30% of base flow). Our spatially explicit habitat models achieved classification accuracies between 85% and 91%, depending on the snorkel survey and creek. Water depth was the most significant covariate in our models, followed by substrate, Froude number, velocity, and water temperature. Hydraulic simulations showed 2-11% gains in dace habitat when flows were increased by 30%, and 8-32% losses when flows were reduced by 30%. To ensure the health and survival of Moapa dace and the Muddy River ecosystem, groundwater and surface-water withdrawals and diversions need to be carefully monitored, while fully implementing a proactive conservation strategy.

  17. Metabolic disruption identified in the Huntington's disease transgenic sheep model.

    Science.gov (United States)

    Handley, Renee R; Reid, Suzanne J; Patassini, Stefano; Rudiger, Skye R; Obolonkin, Vladimir; McLaughlan, Clive J; Jacobsen, Jessie C; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2016-02-11

    Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease.

  18. Integrated network analysis identifies fight-club nodes as a class of hubs encompassing key putative switch genes that induce major transcriptome reprogramming during grapevine development.

    Science.gov (United States)

    Palumbo, Maria Concetta; Zenoni, Sara; Fasoli, Marianna; Massonnet, Mélanie; Farina, Lorenzo; Castiglione, Filippo; Pezzotti, Mario; Paci, Paola

    2014-12-01

    We developed an approach that integrates different network-based methods to analyze the correlation network arising from large-scale gene expression data. By studying grapevine (Vitis vinifera) and tomato (Solanum lycopersicum) gene expression atlases and a grapevine berry transcriptomic data set during the transition from immature to mature growth, we identified a category named "fight-club hubs" characterized by a marked negative correlation with the expression profiles of neighboring genes in the network. A special subset named "switch genes" was identified, with the additional property of many significant negative correlations outside their own group in the network. Switch genes are involved in multiple processes and include transcription factors that may be considered master regulators of the previously reported transcriptome remodeling that marks the developmental shift from immature to mature growth. All switch genes, expressed at low levels in vegetative/green tissues, showed a significant increase in mature/woody organs, suggesting a potential regulatory role during the developmental transition. Finally, our analysis of tomato gene expression data sets showed that wild-type switch genes are downregulated in ripening-deficient mutants. The identification of known master regulators of tomato fruit maturation suggests our method is suitable for the detection of key regulators of organ development in different fleshy fruit crops.

  19. Ocean Heat and Carbon Uptake in Transient Climate Change: Identifying Model Uncertainty

    Science.gov (United States)

    Romanou, Anastasia; Marshall, John

    2015-01-01

    Global warming on decadal and centennial timescales is mediated and ameliorated by the oceansequestering heat and carbon into its interior. Transient climate change is a function of the efficiency by whichanthropogenic heat and carbon are transported away from the surface into the ocean interior (Hansen et al. 1985).Gregory and Mitchell (1997) and Raper et al. (2002) were the first to identify the importance of the ocean heat uptakeefficiency in transient climate change. Observational estimates (Schwartz 2012) and inferences from coupledatmosphere-ocean general circulation models (AOGCMs; Gregory and Forster 2008; Marotzke et al. 2015), suggest thatocean heat uptake efficiency on decadal timescales lies in the range 0.5-1.5 W/sq m/K and is thus comparable to theclimate feedback parameter (Murphy et al. 2009). Moreover, the ocean not only plays a key role in setting the timing ofwarming but also its regional patterns (Marshall et al. 2014), which is crucial to our understanding of regional climate,carbon and heat uptake, and sea-level change. This short communication is based on a presentation given by A.Romanou at a recent workshop, Oceans Carbon and Heat Uptake: Uncertainties and Metrics, co-hosted by US CLIVARand OCB. As briefly reviewed below, we have incomplete but growing knowledge of how ocean models used in climatechange projections sequester heat and carbon into the interior. To understand and thence reduce errors and biases inthe ocean component of coupled models, as well as elucidate the key mechanisms at work, in the final section we outlinea proposed model intercomparison project named FAFMIP. In FAFMIP, coupled integrations would be carried out withprescribed overrides of wind stress and freshwater and heat fluxes acting at the sea surface.

  20. Identifying missing dictionary entries with frequency-conserving context models

    Science.gov (United States)

    Williams, Jake Ryland; Clark, Eric M.; Bagrow, James P.; Danforth, Christopher M.; Dodds, Peter Sheridan

    2015-10-01

    In an effort to better understand meaning from natural language texts, we explore methods aimed at organizing lexical objects into contexts. A number of these methods for organization fall into a family defined by word ordering. Unlike demographic or spatial partitions of data, these collocation models are of special importance for their universal applicability. While we are interested here in text and have framed our treatment appropriately, our work is potentially applicable to other areas of research (e.g., speech, genomics, and mobility patterns) where one has ordered categorical data (e.g., sounds, genes, and locations). Our approach focuses on the phrase (whether word or larger) as the primary meaning-bearing lexical unit and object of study. To do so, we employ our previously developed framework for generating word-conserving phrase-frequency data. Upon training our model with the Wiktionary, an extensive, online, collaborative, and open-source dictionary that contains over 100 000 phrasal definitions, we develop highly effective filters for the identification of meaningful, missing phrase entries. With our predictions we then engage the editorial community of the Wiktionary and propose short lists of potential missing entries for definition, developing a breakthrough, lexical extraction technique and expanding our knowledge of the defined English lexicon of phrases.

  1. Identifying hypoxia in a newborn piglet model using urinary NMR metabolomic profiling.

    Directory of Open Access Journals (Sweden)

    Christopher Skappak

    Full Text Available Establishing the severity of hypoxic insult during the delivery of a neonate is key step in the determining the type of therapy administered. While successful therapy is present, current methods for assessing hypoxic injuries in the neonate are limited. Urine Nuclear Magnetic Resonance (NMR metabolomics allows for the rapid non-invasive assessment of a multitude breakdown products of physiological processes. In a newborn piglet model of hypoxia, we used NMR spectroscopy to determine the levels of metabolites in urine samples, which were correlated with physiological measurements. Using PLS-DA analysis, we identified 13 urinary metabolites that differentiated hypoxic versus nonhypoxic animals (1-methylnicotinamide, 2-oxoglutarate, alanine, asparagine, betaine, citrate, creatine, fumarate, hippurate, lactate, N-acetylglycine, N-carbamoyl-β-alanine, and valine. Using this metabolomic profile, we then were able to blindly identify hypoxic animals correctly 84% of the time compared to nonhypoxic controls. This was better than using physiologic measures alone. Metabolomic profiling of urine has potential for identifying neonates that have undergone episodes of hypoxia.

  2. Thermodynamic modeling of Cu–Ni–Y system coupled with key experiments

    Energy Technology Data Exchange (ETDEWEB)

    Mezbahul-Islam, Mohammad [Department of Mechanical Engineering, Concordia University, 1455 de Maisonneuve Blvd West, Montreal, Quebec, Montreal H3G 1M8 (Canada); Medraj, Mamoun, E-mail: mmedraj@encs.concordia.ca [Department of Mechanical Engineering, Concordia University, 1455 de Maisonneuve Blvd West, Montreal, Quebec, Montreal H3G 1M8 (Canada); Department of Mechanical and Materials Engineering, Masdar Institute of Science and Technology, Masdar City, Abu Dhabi (United Arab Emirates)

    2015-03-01

    A complete thermodynamic description of the Cu–Ni–Y ternary system has been obtained using the CALPHAD (CALculation of PHAse Diagram) approach. Ternary solubility of the third element in the binary compounds in the Cu–Ni–Y system is described using sublattice model within the compound energy formalism (CEF) to take into account the recently reported experimental solubility ranges. The modified quasi-chemical model (MQM) has been used to describe the liquid phase in order to account for the presence of short range ordering properly. To study the melting behavior of the Cu–Ni–Y alloys and to verify the consistency of the thermodynamic model with experimental results, 10 key samples were prepared and the phase transformation temperatures were measured using differential scanning calorimeter (DSC). The microstructural characterization and crystallographic analysis of the alloys were carried out using scanning electron microscopy (SEM) coupled with WDS analysis and X-ray diffraction (XRD). Several vertical sections, liquidus projection and isothermal section at 973 K have been calculated and found to be in good agreement with the current experimental data as well as with the literature. - Highlights: • Thermodynamic modeling of the Cu–Ni–Y system has been performed. • Ternary solubilities of the binary compounds have been reproduced. • Modified quasi-chemical model is used to model the liquid phase. • DSC experiments are performed on selected key alloys. • The calculations are consistent with the experimental results.

  3. Summary of the key features of seven biomathematical models of human fatigue and performance

    Science.gov (United States)

    Mallis, Melissa M.; Mejdal, Sig; Nguyen, Tammy T.; Dinges, David F.

    2004-01-01

    BACKGROUND: Biomathematical models that quantify the effects of circadian and sleep/wake processes on the regulation of alertness and performance have been developed in an effort to predict the magnitude and timing of fatigue-related responses in a variety of contexts (e.g., transmeridian travel, sustained operations, shift work). This paper summarizes key features of seven biomathematical models reviewed as part of the Fatigue and Performance Modeling Workshop held in Seattle, WA, on June 13-14, 2002. The Workshop was jointly sponsored by the National Aeronautics and Space Administration, U.S. Department of Defense, U.S. Army Medical Research and Materiel Command, Office of Naval Research, Air Force Office of Scientific Research, and U.S. Department of Transportation. METHODS: An invitation was sent to developers of seven biomathematical models that were commonly cited in scientific literature and/or supported by government funding. On acceptance of the invitation to attend the Workshop, developers were asked to complete a survey of the goals, capabilities, inputs, and outputs of their biomathematical models of alertness and performance. Data from the completed surveys were summarized and juxtaposed to provide a framework for comparing features of the seven models. RESULTS: Survey responses revealed that models varied greatly relative to their reported goals and capabilities. While all modelers reported that circadian factors were key components of their capabilities, they differed markedly with regard to the roles of sleep and work times as input factors for prediction: four of the seven models had work time as their sole input variable(s), while the other three models relied on various aspects of sleep timing for model input. Models also differed relative to outputs: five sought to predict results from laboratory experiments, field, and operational data, while two models were developed without regard to predicting laboratory experimental results. All modelers

  4. Improving Control of Antibiotic-Resistant Gonorrhea by Integrating Research Agendas Across Disciplines: Key Questions Arising From Mathematical Modeling.

    Science.gov (United States)

    Grad, Yonatan H; Goldstein, Edward; Lipsitch, Marc; White, Peter J

    2016-03-15

    The rise in gonococcal antibiotic resistance and the threat of untreatable infection are focusing attention on strategies to limit the spread of drug-resistant gonorrhea. Mathematical models provide a framework to link the natural history of infection and patient behavior to epidemiological outcomes and can be used to guide research and enhance the public health impact of interventions. While limited knowledge of key disease parameters and networks of spread has impeded development of operational models of gonococcal transmission, new tools in gonococcal surveillance may provide useful data to aid tracking and modeling. Here, we highlight critical questions in the management of gonorrhea that can be addressed by mathematical models and identify key data needs. Our overarching aim is to articulate a shared agenda across gonococcus-related fields from microbiology to epidemiology that will catalyze a comprehensive evidence-based clinical and public health strategy for management of gonococcal infections and antimicrobial resistance. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Identifying student and teacher difficulties in interpreting atomic spectra using a quantum model of emission and absorption of radiation

    Science.gov (United States)

    Savall-Alemany, Francisco; Domènech-Blanco, Josep Lluís; Guisasola, Jenaro; Martínez-Torregrosa, Joaquín

    2016-06-01

    Our study sets out to identify the difficulties that high school students, teachers, and university students encounter when trying to explain atomic spectra. To do so, we identify the key concepts that any quantum model for the emission and absorption of electromagnetic radiation must include to account for the gas spectra and we then design two questionnaires, one for teachers and the other for students. By analyzing the responses, we conclude that (i) teachers lack a quantum model for the emission and absorption of electromagnetic radiation capable of explaining the spectra, (ii) teachers and students share the same difficulties, and (iii) these difficulties concern the model of the atom, the model of radiation, and the model of the interaction between them.

  6. Modelling evapotranspiration during precipitation deficits: identifying critical processes in a land surface model

    Science.gov (United States)

    Ukkola, Anna M.; Pitman, Andy J.; Decker, Mark; De Kauwe, Martin G.; Abramowitz, Gab; Kala, Jatin; Wang, Ying-Ping

    2016-06-01

    Surface fluxes from land surface models (LSMs) have traditionally been evaluated against monthly, seasonal or annual mean states. The limited ability of LSMs to reproduce observed evaporative fluxes under water-stressed conditions has been previously noted, but very few studies have systematically evaluated these models during rainfall deficits. We evaluated latent heat fluxes simulated by the Community Atmosphere Biosphere Land Exchange (CABLE) LSM across 20 flux tower sites at sub-annual to inter-annual timescales, in particular focusing on model performance during seasonal-scale rainfall deficits. The importance of key model processes in capturing the latent heat flux was explored by employing alternative representations of hydrology, leaf area index, soil properties and stomatal conductance. We found that the representation of hydrological processes was critical for capturing observed declines in latent heat during rainfall deficits. By contrast, the effects of soil properties, LAI and stomatal conductance were highly site-specific. Whilst the standard model performs reasonably well at annual scales as measured by common metrics, it grossly underestimates latent heat during rainfall deficits. A new version of CABLE, with a more physically consistent representation of hydrology, captures the variation in the latent heat flux during seasonal-scale rainfall deficits better than earlier versions, but remaining biases point to future research needs. Our results highlight the importance of evaluating LSMs under water-stressed conditions and across multiple plant functional types and climate regimes.

  7. The Key Variables for the Development of a Care Model for Stroke

    Directory of Open Access Journals (Sweden)

    Stavrianopoulos T.

    2011-10-01

    Full Text Available Introduction Stroke is a major cause of death, threatened and reduced health, and a patient’s dependence on support after the acute phase. The increase in knowledge of neurological recovery after a stroke has led to new treatment strategies, where the importance of the physical environment and rehabilitation is on par with the importance of the medical treatment. It is crucial that the whole stroke team is involved in assessing, planning, and evaluating the care provided. Aim The presentation of the variables that are needed for the development of a general model of care for stroke. Material and Methods Method was used is to search electronic databases (MEDLINE, CINAHL for a review of international literature to 2009 and became selection of books, articles and studies from libraries. The search was done the December of 2010. Results The key variables to develop a model of care are: the care planning, the team culture, the care culture, the professional knowledge, the quality of space, the observation and assessment, the patient participation and the inter-professional teamwork. Conclusions The model presents stroke care as a complex system, with many feedback relationships between key variables for care. The development of the model, with the contributions of existing literature, enables further tests in practice and improvements in stroke care and further refinement of variables which include the model of care.

  8. Pointing, looking at, and pressing keys: A diffusion model account of response modality.

    Science.gov (United States)

    Gomez, Pablo; Ratcliff, Roger; Childers, Russ

    2015-12-01

    Accumulation of evidence models of perceptual decision making have been able to account for data from a wide range of domains at an impressive level of precision. In particular, Ratcliff's (1978) diffusion model has been used across many different 2-choice tasks in which the response is executed via a key-press. In this article, we present 2 experiments in which we used a letter-discrimination task exploring 3 central aspects of a 2-choice task: the discriminability of the stimulus, the modality of the response execution (eye movement, key pressing, and pointing on a touchscreen), and the mapping of the response areas for the eye movement and the touchscreen conditions (consistent vs. inconsistent). We fitted the diffusion model to the data from these experiments and examined the behavior of the model's parameters. Fits of the model were consistent with the hypothesis that the same decision mechanism is used in the task with 3 different response methods. Drift rates are affected by the duration of the presentation of the stimulus while the response execution time changed as a function of the response modality.

  9. UNIVERSITY INNOVATION INFRASTRUCTURE MODEL AS A KEY PART OF A TERRITORAL CLUST

    Directory of Open Access Journals (Sweden)

    Nataliya P. Ivashchenko

    2015-01-01

    Full Text Available Over the recent decades there have been increasing efforts by developing countries to reduce the economic gap between developed and developing countries. Asian and Northern European countries demonstrate good progress in these areas.Sweden,Denmark,Chinashow stable high economic indicators that have been achieved by targeted government programs. These programs were aimed at creating a new type of economy based on knowledge and new technologies. Given the success of these countries, a number of developing countries, whose economies are dependent on resources, today, are looking to repeat their way; those countries areRussia,Indonesia,BrazilandChile. The modernization of the economy and the formation of innovative economy are key objectives of the state policies of these countries. The research by leading economists and scientists led to the conclusion that the regional level of national economy plays a key role in formation of knowledgebase economy, which indicates the need to differentiate the innovation policy of the state depending on the economy parameters of each region. This paper presents a model of the first stage of the formation of the entrepreneurialuniversityUniversityinnovation infrastructure model, which is a key part of a territoral cluster. The article consists of five parts. The first part covers the analysis of the two main models of regional development: clustering theory and Triple Helix. This section describes a positive result, which is achieved by using these models simultaneously. The second part of the article shows the importance and the role of the entrepreneurial university in the formation of innovative clusters. It will be explained how and under what conditions this formation is achieved. The third part of this paper will present University innovation infrastructure model. The fourth part will examine the practical first steps to create a cluster "Vorob’evi Gori" on the basis of theMoscowStateUniversity. The fifth

  10. Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Philip W. Brownjohn

    2017-04-01

    Full Text Available Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP processing and the accumulation of APP-derived amyloid β (Aβ peptides are key processes in Alzheimer's disease (AD. We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation.

  11. Modeling the pairwise key distribution scheme in the presence of unreliable links

    CERN Document Server

    Yagan, Osman

    2011-01-01

    We investigate the secure connectivity of wireless sensor networks under the pairwise key distribution scheme of Chan et al.. Unlike recent work which was carried out under the assumption of full visibility, here we assume a (simplified) communication model where unreliable wireless links are represented as on/off channels. We present conditions on how to scale the model parameters so that the network i) has no secure node which is isolated and ii) is securely connected, both with high probability when the number of sensor nodes becomes large. The results are given in the form of zero-one laws, and exhibit significant differences with corresponding results in the full visibility case. Through simulations these zero-one laws are shown to be valid also under a more realistic communication model, i.e., the disk model.

  12. Integrating fire with hydrological projections: model evaluation to identify uncertainties and tradeoffs in model complexity

    Science.gov (United States)

    Kennedy, M.; McKenzie, D.

    2013-12-01

    It is imperative for resource managers to understand how a changing climate might modify future watershed and hydrological processes, and such an understanding is incomplete if disturbances such as fire are not integrated with hydrological projections. Can a robust fire spread model be developed that approximates patterns of fire spread in response to varying topography wind patterns, and fuel loads and moistures, without requiring intensive calibration to each new study area or time frame? We assessed the performance of a stochastic model of fire spread (WMFire), integrated with the Regional Hydro-Ecological Simulation System (RHESSys), for projecting the effects of climatic change on mountain watersheds. We first use Monte Carlo inference to determine that the fire spread model is able to replicate the spatial pattern of fire spread for a contemporary wildfire in Washington State (the Tripod fire), measured by the lacunarity and fractal dimension of the fire. We then integrate a version of WMFire able to replicate the contemporary wildfire with RHESSys and simulate a New Mexico watershed over the calibration period of RHESSys (1941-1997). In comparing the fire spread model to a single contemporary wildfire we found issues in parameter identifiability for several of the nine parameters, due to model input uncertainty and insensitivity of the mathematical function to certain ranges of the parameter values. Model input uncertainty is caused by the inherent difficulty in reconstructing fuel loads and fuel moistures for a fire event after the fire has occurred, as well as by issues in translating variables relevant to hydrological processes produced by the hydrological model to those known to affect fire spread and fire severity. The first stage in the model evaluation aided the improvement of the model in both of these regards. In transporting the model to a new landscape in order to evaluate fire regimes in addition to patterns of fire spread, we find reasonable

  13. Modeling halotropism: a key role for root tip architecture and reflux loop remodeling in redistributing auxin.

    Science.gov (United States)

    van den Berg, Thea; Korver, Ruud A; Testerink, Christa; Ten Tusscher, Kirsten H W J

    2016-09-15

    A key characteristic of plant development is its plasticity in response to various and dynamically changing environmental conditions. Tropisms contribute to this flexibility by allowing plant organs to grow from or towards environmental cues. Halotropism is a recently described tropism in which plant roots bend away from salt. During halotropism, as in most other tropisms, directional growth is generated through an asymmetric auxin distribution that generates differences in growth rate and hence induces bending. Here, we develop a detailed model of auxin transport in the Arabidopsis root tip and combine this with experiments to investigate the processes generating auxin asymmetry during halotropism. Our model points to the key role of root tip architecture in allowing the decrease in PIN2 at the salt-exposed side of the root to result in a re-routing of auxin to the opposite side. In addition, our model demonstrates how feedback of auxin on the auxin transporter AUX1 amplifies this auxin asymmetry, while a salt-induced transient increase in PIN1 levels increases the speed at which this occurs. Using AUX1-GFP imaging and pin1 mutants, we experimentally confirmed these model predictions, thus expanding our knowledge of the cellular basis of halotropism.

  14. [A model for evaluation of key measures for control of chikungunya fever outbreak in China].

    Science.gov (United States)

    Zhao, Jin; Liu, Ruchun; Chen, Shuilian; Chen, Tianmu

    2015-11-01

    To analyze the transmission pattern of Chikungunya (CHIK) fever in community and evaluate the effectiveness of mosquito control, case isolation and other key control measures by using ordinary differential equation (ODE) model. According to natural history of CHIK, an ODE model for the epidemiological analysis of CHIK outbreak was established. The key parameters of the model were obtained by fitting the model with reported outbreak data of the first CHIK outbreak in China. Then the outbreak characteristics without intervention, the effectiveness of mosquito control and case isolation were simulated. Without intervention, an imported case would cause an outbreak in a community with population of 11 000, and cumulative case number would exceed 941 when the total attack rate was 8.55%. The results of our simulation revealed that the effectiveness of case isolation was not perfect enough when it was implemented alone. Although the number of cases could be decreased by case isolation, the duration of outbreak would not be shortened. Differently, the effectiveness of mosquito control was remarkable. In addition, the earlier the measure was implemented, the better the effectiveness would be. The effectiveness of mosquito control plus case isolation was same with mosquito control. To control a CHIK outbreak, mosquito control is the most recommended measures. However, case isolation is also necessary as the supplementation of mosquito control.

  15. Preferential Attachment Model with Degree Bound and its Application to Key Predistribution in WSN

    CERN Document Server

    Ruj, Sushmita

    2016-01-01

    Preferential attachment models have been widely studied in complex networks, because they can explain the formation of many networks like social networks, citation networks, power grids, and biological networks, to name a few. Motivated by the application of key predistribution in wireless sensor networks (WSN), we initiate the study of preferential attachment with degree bound. Our paper has two important contributions to two different areas. The first is a contribution in the study of complex networks. We propose preferential attachment model with degree bound for the first time. In the normal preferential attachment model, the degree distribution follows a power law, with many nodes of low degree and a few nodes of high degree. In our scheme, the nodes can have a maximum degree $d_{\\max}$, where $d_{\\max}$ is an integer chosen according to the application. The second is in the security of wireless sensor networks. We propose a new key predistribution scheme based on the above model. The important features ...

  16. Coupling process-based models and plant architectural models: A key issue for simulating crop production

    NARCIS (Netherlands)

    Reffye, de P.; Heuvelink, E.; Guo, Y.; Hu, B.G.; Zhang, B.G.

    2009-01-01

    Process-Based Models (PBMs) can successfully predict the impact of environmental factors (temperature, light, CO2, water and nutrients) on crop growth and yield. These models are used widely for yield prediction and optimization of water and nutrient supplies. Nevertheless, PBMs do not consider plan

  17. Breaking a virus: Identifying molecular level failure modes of a viral capsid by multiscale modeling

    Science.gov (United States)

    Krishnamani, V.; Globisch, C.; Peter, C.; Deserno, M.

    2016-07-01

    We use coarse-grained (CG) simulations to study the deformation of empty Cowpea Chlorotic Mottle Virus (CCMV) capsids under uniaxial compression, from the initial elastic response up to capsid breakage. Our CG model is based on the MARTINI force field and has been amended by a stabilizing elastic network, acting only within individual proteins, that was tuned to capture the fluctuation spectrum of capsid protein dimers, obtained from all atom simulations. We have previously shown that this model predicts force-compression curves that match AFM indentation experiments on empty CCMV capsids. Here we investigate details of the actual breaking events when the CCMV capsid finally fails. We present a symmetry classification of all relevant protein contacts and show that they differ significantly in terms of stability. Specifically, we show that interfaces which break readily are precisely those which are believed to form last during assembly, even though some of them might share the same contacts as other non-breaking interfaces. In particular, the interfaces that form pentamers of dimers never break, while the virtually identical interfaces within hexamers of dimers readily do. Since these units differ in the large-scale geometry and, most noticeably, the cone-angle at the center of the 5- or 6-fold vertex, we propose that the hexameric unit fails because it is pre-stressed. This not only suggests that hexamers of dimers form less frequently during the early stages of assembly; it also offers a natural explanation for the well-known β-barrel motif at the hexameric center as a post-aggregation stabilization mechanism. Finally, we identify those amino acid contacts within all key protein interfaces that are most persistent during compressive deformation of the capsid, thereby providing potential targets for mutation studies aiming to elucidate the key contacts upon which overall stability rests.

  18. Breaking a virus: Identifying molecular level failure modes of a viral capsid by multiscale modeling

    Science.gov (United States)

    Krishnamani, V.; Globisch, C.; Peter, C.; Deserno, M.

    2016-10-01

    We use coarse-grained (CG) simulations to study the deformation of empty Cowpea Chlorotic Mottle Virus (CCMV) capsids under uniaxial compression, from the initial elastic response up to capsid breakage. Our CG model is based on the MARTINI force field and has been amended by a stabilizing elastic network, acting only within individual proteins, that was tuned to capture the fluctuation spectrum of capsid protein dimers, obtained from all atom simulations. We have previously shown that this model predicts force-compression curves that match AFM indentation experiments on empty CCMV capsids. Here we investigate details of the actual breaking events when the CCMV capsid finally fails. We present a symmetry classification of all relevant protein contacts and show that they differ significantly in terms of stability. Specifically, we show that interfaces which break readily are precisely those which are believed to form last during assembly, even though some of them might share the same contacts as other non-breaking interfaces. In particular, the interfaces that form pentamers of dimers never break, while the virtually identical interfaces within hexamers of dimers readily do. Since these units differ in the large-scale geometry and, most noticeably, the cone-angle at the center of the 5- or 6-fold vertex, we propose that the hexameric unit fails because it is pre-stressed. This not only suggests that hexamers of dimers form less frequently during the early stages of assembly; it also offers a natural explanation for the well-known β-barrel motif at the hexameric center as a post-aggregation stabilization mechanism. Finally, we identify those amino acid contacts within all key protein interfaces that are most persistent during compressive deformation of the capsid, thereby providing potential targets for mutation studies aiming to elucidate the key contacts upon which overall stability rests.

  19. Modeling succession of key resource-harvesting traits of mixotrophic plankton

    DEFF Research Database (Denmark)

    Berge, Terje; Chakraborty, Subhendu; Hansen, Per Juel

    2017-01-01

    -based model for mixotrophy with three key resource-harvesting traits: photosynthesis, phagotrophy and inorganic nutrient uptake, which predicts the trophic strategy of species throughout the seasonal cycle. Assuming that simple carbohydrates from photosynthesis fuel respiration, and feeding primarily provides...... in the spring and increased phagotrophy during the summer, reflecting general seasonal succession patterns of temperate waters. Our trait-based model presents a simple and general approach for the inclusion of mixotrophy, succession and evolution in ecosystem models.The ISME Journal advance online publication......Unicellular eukaryotes make up the base of the ocean food web and exist as a continuum in trophic strategy from pure heterotrophy (phagotrophic zooplankton) to pure photoautotrophy (‘phytoplankton’), with a dominance of mixotrophic organisms combining both strategies. Here we formulate a trait...

  20. Key Technology Research on Open Architecture for The Sharing of Heterogeneous Geographic Analysis Models

    Science.gov (United States)

    Yue, S. S.; Wen, Y. N.; Lv, G. N.; Hu, D.

    2013-10-01

    In recent years, the increasing development of cloud computing technologies laid critical foundation for efficiently solving complicated geographic issues. However, it is still difficult to realize the cooperative operation of massive heterogeneous geographical models. Traditional cloud architecture is apt to provide centralized solution to end users, while all the required resources are often offered by large enterprises or special agencies. Thus, it's a closed framework from the perspective of resource utilization. Solving comprehensive geographic issues requires integrating multifarious heterogeneous geographical models and data. In this case, an open computing platform is in need, with which the model owners can package and deploy their models into cloud conveniently, while model users can search, access and utilize those models with cloud facility. Based on this concept, the open cloud service strategies for the sharing of heterogeneous geographic analysis models is studied in this article. The key technology: unified cloud interface strategy, sharing platform based on cloud service, and computing platform based on cloud service are discussed in detail, and related experiments are conducted for further verification.

  1. How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia

    Science.gov (United States)

    Freeman, Daniel; Dunn, Graham; Murray, Robin M.; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M.; Harrison, Paul J.; Harmer, Catherine J.; Cowen, Philip; Morrison, Paul D.

    2015-01-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis—∆9-tetrahydrocannabinol (THC)—causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. PMID:25031222

  2. How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

    Science.gov (United States)

    Freeman, Daniel; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M; Harrison, Paul J; Harmer, Catherine J; Cowen, Philip; Morrison, Paul D

    2015-03-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences.

  3. Identifying the key factors in increasing recycling and reducing residual household waste: a case study of the Flemish region of Belgium.

    Science.gov (United States)

    Gellynck, X; Jacobsen, R; Verhelst, P

    2011-10-01

    The competent waste authority in the Flemish region of Belgium created the 'Implementation plan household waste 2003-2007' and the 'Implementation plan sustainable management 2010-2015' to comply with EU regulation. It incorporates European and regional requirements and describes strategies, goals, actions and instruments for the collection and treatment of household waste. The central mandatory goal is to reduce and maintain the amount of residual household waste to 150 kg per capita per year between 2010-2015. In literature, a reasonable body of information has been published on the effectiveness and efficiency of a variety of policy instruments, but the information is complex, often contradictory and difficult to interpret. The objective of this paper is to identify, through the development of a binary logistic regression model, those variables of the waste collection scheme that help municipalities to reach the mandatory 150 kg goal. The model covers a number of variables for household characteristics, provision of recycling services, frequency of waste collection and charging for waste services. This paper, however, is not about waste prevention and reuse. The dataset originates from 2003. Four out of 12 variables in the model contributed significantly: income per capita, cost of residual waste collection, collection frequency and separate curbside collection of organic waste.

  4. Key Issues in Modeling of Complex 3D Structures from Video Sequences

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

    Full Text Available Construction of three-dimensional structures from video sequences has wide applications for intelligent video analysis. This paper summarizes the key issues of the theory and surveys the recent advances in the state of the art. Reconstruction of a scene object from video sequences often takes the basic principle of structure from motion with an uncalibrated camera. This paper lists the typical strategies and summarizes the typical solutions or algorithms for modeling of complex three-dimensional structures. Open difficult problems are also suggested for further study.

  5. Muninn: A versioning flash key-value store using an object-based storage model

    OpenAIRE

    Kang, Y.; Pitchumani, R; Marlette, T; Miller, El

    2014-01-01

    While non-volatile memory (NVRAM) devices have the po-tential to alleviate the trade-off between performance, scal-ability, and energy in storage and memory subsystems, a block interface and storage subsystems designed for slow I/O devices make it difficult to efficiently exploit NVRAMs in a portable and extensible way. We propose an object-based storage model as a way of addressing the shortfalls of the current interfaces. Through the design of Muninn, an object-based versioning key-value st...

  6. Key factors regulating the mass delivery of macromolecules to model cell membranes

    DEFF Research Database (Denmark)

    Campbell, Richard A.; Watkins, Erik B.; Jagalski, Vivien

    2014-01-01

    We show that both gravity and electrostatics are key factors regulating interactions between model cell membranes and self-assembled liquid crystalline aggregates of dendrimers and phospholipids. The system is a proxy for the trafficking of reservoirs of therapeutic drugs to cell membranes for slow...... diffusion and continuous delivery. Neutron reflectometry measurements were carried out on supported lipid bilayers of varying charge and on hydrophilic silica surfaces. Translocation of the macromolecule across the membrane and adsorption of the lamellar aggregates occur only when the membrane (1...... of the aggregates to activate endocytosis pathways on specific cell types is discussed in the context of targeted drug delivery applications....

  7. Implementing the Five-A Model of Technical Refinement: Key Roles of the Sport Psychologist.

    Science.gov (United States)

    Carson, Howie J; Collins, Dave

    2016-10-01

    There is increasing evidence for the significant contribution provided by sport psychologists within applied coaching environments. However, this rarely considers their skills/knowledge being applied when refining athletes' already learned and well-established motor skills. Therefore, this article focuses on how a sport psychologist might assist a coach and athlete to implement long-term permanent and pressure proof refinements. It highlights key contributions at each stage of the Five-A model-designed to deliver these important outcomes-providing both psychomotor and psychosocial input to the support delivery. By employing these recommendations, sport psychologists can make multiple positive contributions to completion of this challenging task.

  8. The identifiability of parameters in a water quality model of the Biebrza River, Poland

    NARCIS (Netherlands)

    Perk, van der M.; Bierkens, M.F.P.

    1997-01-01

    The identifiability of model parameters of a steady state water quality model of the Biebrza River and the resulting variation in model results was examined by applying the Monte Carlo method which combines calibration, identifiability analysis, uncertainty analysis, and sensitivity analysis. The wa

  9. Are there pollination syndromes in the Australian epacrids (Ericaceae: Styphelioideae)? A novel statistical method to identify key floral traits per syndrome.

    Science.gov (United States)

    Johnson, Karen A

    2013-07-01

    Convergent floral traits hypothesized as attracting particular pollinators are known as pollination syndromes. Floral diversity suggests that the Australian epacrid flora may be adapted to pollinator type. Currently there are empirical data on the pollination systems for 87 species (approx. 15 % of Australian epacrids). This provides an opportunity to test for pollination syndromes and their important morphological traits in an iconic element of the Australian flora. Data on epacrid-pollinator relationships were obtained from published literature and field observation. A multivariate approach was used to test whether epacrid floral attributes related to pollinator profiles. Statistical classification was then used to rank floral attributes according to their predictive value. Data sets excluding mixed pollination systems were used to test the predictive power of statistical classification to identify pollination models. Floral attributes are correlated with bird, fly and bee pollination. Using floral attributes identified as correlating with pollinator type, bird pollination is classified with 86 % accuracy, red flowers being the most important predictor. Fly and bee pollination are classified with 78 and 69 % accuracy, but have a lack of individually important floral predictors. Excluding mixed pollination systems improved the accuracy of the prediction of both bee and fly pollination systems. Although most epacrids have generalized pollination systems, a correlation between bird pollination and red, long-tubed epacrids is found. Statistical classification highlights the relative importance of each floral attribute in relation to pollinator type and proves useful in classifying epacrids to bird, fly and bee pollination systems.

  10. Dynamic ligand-based pharmacophore modeling and virtual screening to identify mycobacterial cyclopropane synthase inhibitors

    Indian Academy of Sciences (India)

    CHINMAYEE CHOUDHURY; U DEVA PRIYAKUMAR; G NARAHARI SASTRY

    2016-05-01

    Multidrug resistance in Mycobacterium tuberculosis (M. Tb) and its coexistence with HIV arethe biggest therapeutic challenges in anti-M. Tb drug discovery. The current study reports a Virtual Screening(VS) strategy to identify potential inhibitors of Mycobacterial cyclopropane synthase (CmaA1), an importantM. Tb target considering the above challenges. Five ligand-based pharmacophore models were generatedfrom 40 different conformations of the cofactors of CmaA1 taken from molecular dynamics (MD) simulationstrajectories of CmaA1. The screening abilities of these models were validated by screening 23 inhibitors and1398 non-inhibitors of CmaA1. A VS protocol was designed with four levels of screening i.e., ligand-basedpharmacophore screening, structure-based pharmacophore screening, docking and absorption, distribution,metabolism, excretion and the toxicity (ADMET) filters. In an attempt towards repurposing the existing drugsto inhibit CmaA1, 6,429 drugs reported in DrugBank were considered for screening. To find compounds thatinhibit multiple targets of M. Tb as well as HIV, we also chose 701 and 11,109 compounds showing activitybelow 1 μM range on M. Tb and HIV cell lines, respectively, collected from ChEMBL database. Thus, a totalof 18,239 compounds were screened against CmaA1, and 12 compounds were identified as potential hits forCmaA1 at the end of the fourth step. Detailed analysis of the structures revealed these compounds to interactwith key active site residues of CmaA1.

  11. Global identifiability of linear compartmental models--a computer algebra algorithm.

    Science.gov (United States)

    Audoly, S; D'Angiò, L; Saccomani, M P; Cobelli, C

    1998-01-01

    A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model order. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows for the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.

  12. Quantifying Key Climate Parameter Uncertainties Using an Earth System Model with a Dynamic 3D Ocean

    Science.gov (United States)

    Olson, R.; Sriver, R. L.; Goes, M. P.; Urban, N.; Matthews, D.; Haran, M.; Keller, K.

    2011-12-01

    Climate projections hinge critically on uncertain climate model parameters such as climate sensitivity, vertical ocean diffusivity and anthropogenic sulfate aerosol forcings. Climate sensitivity is defined as the equilibrium global mean temperature response to a doubling of atmospheric CO2 concentrations. Vertical ocean diffusivity parameterizes sub-grid scale ocean vertical mixing processes. These parameters are typically estimated using Intermediate Complexity Earth System Models (EMICs) that lack a full 3D representation of the oceans, thereby neglecting the effects of mixing on ocean dynamics and meridional overturning. We improve on these studies by employing an EMIC with a dynamic 3D ocean model to estimate these parameters. We carry out historical climate simulations with the University of Victoria Earth System Climate Model (UVic ESCM) varying parameters that affect climate sensitivity, vertical ocean mixing, and effects of anthropogenic sulfate aerosols. We use a Bayesian approach whereby the likelihood of each parameter combination depends on how well the model simulates surface air temperature and upper ocean heat content. We use a Gaussian process emulator to interpolate the model output to an arbitrary parameter setting. We use Markov Chain Monte Carlo method to estimate the posterior probability distribution function (pdf) of these parameters. We explore the sensitivity of the results to prior assumptions about the parameters. In addition, we estimate the relative skill of different observations to constrain the parameters. We quantify the uncertainty in parameter estimates stemming from climate variability, model and observational errors. We explore the sensitivity of key decision-relevant climate projections to these parameters. We find that climate sensitivity and vertical ocean diffusivity estimates are consistent with previously published results. The climate sensitivity pdf is strongly affected by the prior assumptions, and by the scaling

  13. Key transmission parameters of an institutional outbreak during the 1918 influenza pandemic estimated by mathematical modelling

    Directory of Open Access Journals (Sweden)

    Nelson Peter

    2006-11-01

    Full Text Available Abstract Aim To estimate the key transmission parameters associated with an outbreak of pandemic influenza in an institutional setting (New Zealand 1918. Methods Historical morbidity and mortality data were obtained from the report of the medical officer for a large military camp. A susceptible-exposed-infectious-recovered epidemiological model was solved numerically to find a range of best-fit estimates for key epidemic parameters and an incidence curve. Mortality data were subsequently modelled by performing a convolution of incidence distribution with a best-fit incidence-mortality lag distribution. Results Basic reproduction number (R0 values for three possible scenarios ranged between 1.3, and 3.1, and corresponding average latent period and infectious period estimates ranged between 0.7 and 1.3 days, and 0.2 and 0.3 days respectively. The mean and median best-estimate incidence-mortality lag periods were 6.9 and 6.6 days respectively. This delay is consistent with secondary bacterial pneumonia being a relatively important cause of death in this predominantly young male population. Conclusion These R0 estimates are broadly consistent with others made for the 1918 influenza pandemic and are not particularly large relative to some other infectious diseases. This finding suggests that if a novel influenza strain of similar virulence emerged then it could potentially be controlled through the prompt use of major public health measures.

  14. Initial Content Validation Results of a New Simulation Model for Flexible Ureteroscopy: The Key-Box.

    Science.gov (United States)

    Villa, Luca; Şener, Tarik Emre; Somani, Bhaskar K; Cloutier, Jonathan; Butticè, Salvatore; Marson, Francesco; Doizi, Steeve; Proietti, Silvia; Traxer, Olivier

    2017-01-01

    We sought to test the content validity of a new training model for flexible ureteroscopy: the Key-Box. Sixteen medical students were randomized to undergo a 10-day training consisting of performing 10 different exercises aimed at learning specific movements with the flexible ureteroscope, and how to catch and release stones with a nitinol basket using the Key-Box (n = 8 students in the training group, n = 8 students in the nontraining control group). Subsequently, an expert endourologist (O.T.) blindly assessed skills acquired by the whole cohort of students through two exercises on ureteroscope manipulation and one exercise on stone capture selected among those used for the training. A performance scale (1-5) assessing different steps of the procedure was used to evaluate each student. Time to complete the exercises was measured. Mann-Whitney Rank Sum test was used for comparisons between the two groups. Mean scores obtained by trained students were significantly higher compared with those obtained by nontrained students (all p six (75%) nontrained students were not able to finish one out of the two exercises on ureteroscope manipulation and the exercise on stone capture, respectively. The mean time to complete the three exercises was 76.3, 69.9, and 107 and 172.5, 137.9, and 168 seconds in the trained and nontrained groups, respectively (all p Box(®) seems to be a valid easy-to-use training model for initiating novel endoscopists to flexible ureteroscopy.

  15. Determining Key Model Parameters of Rapidly Intensifying Hurricane Guillermo(1997) using the Ensemble Kalman Filter

    CERN Document Server

    Godinez, Humberto C; Fierro, Alexandre O; Guimond, Stephen R; Kao, Jim

    2011-01-01

    In this work we present the assimilation of dual-Doppler radar observations for rapidly intensifying hurricane Guillermo (1997) using the Ensemble Kalman Filter (EnKF) to determine key model parameters. A unique aspect of Guillermo was that during the period of radar observations strong convective bursts, attributable to wind shear, formed primarily within the eastern semicircle of the eyewall. To reproduce this observed structure within a hurricane model, background wind shear of some magnitude must be specified; as well as turbulence and surface parameters appropriately specified so that the impact of the shear on the simulated hurricane vortex can be realized. To first illustrate the complex nonlinear interactions induced by changes in these parameters, an ensemble of 120 simulations have been conducted in which individual members were formulated by sampling the parameters within a certain range via a Latin hypercube approach. Next, data from the 120 simulations and two distinct derived fields of observati...

  16. Development of generic key performance indicators for PMBOK® using a 3D project integration model

    Directory of Open Access Journals (Sweden)

    Craig Langston

    2013-12-01

    Full Text Available Since Martin Barnes’ so-called ‘iron triangle’ circa 1969, much debate has occurred over how best to describe the fundamental constraints that underpin project success. This paper develops a 3D project integration model for PMBOK® comprising core constraints of scope, cost, time and risk as a basis to propose six generic key performance indicators (KPIs that articulate successful project delivery. These KPIs are defined as value, efficiency, speed, innovation, complexity and impact and can each be measured objectively as ratios of the core constraints. An overall KPI (denoted as s3/ctr is also derived. The aim in this paper is to set out the case for such a model and to demonstrate how it can be employed to assess the performance of project teams in delivering successful outcomes at various stages in the project life cycle. As part of the model’s development, a new PMBOK® knowledge area concerning environmental management is advanced.

  17. Simulation and Projection of Blocking Highs in Key Regions of the Eurasia by CMIP5 Models

    Science.gov (United States)

    Li, Y.

    2016-12-01

    Previous studies generally hold viewpoint that CMIP5 models underestimate blocking frequency and predict decreasing trend of blockings in 21st century in North Hemisphere (NH). However, regional blocking has its own features, which is different from blockings in NH as a whole. Focusing on three key regions in Eurasia-Ural, Baikal, and Okhotsk where blockings significantly influence weather and climate of East Asia, historical simulations were analyzed to evaluate the performance of the CMIP5 models, and possible changes in the first half 21st century were then predicted using the RCP 4.5 and RCP 8.5 pathways. Comparison with NCEP/NCAR reanalysis (NNR) data revealed that instantaneous blocking frequencies are underestimated in the Ural and Baikal in the whole year and in Okhotsk in summer, but are overestimated in Okhotsk in winter. Overall, the CMIP5 models could largely reproduce character of instantaneous blocking frequency in the Eurasia, with a better performance in winter than in summer. Blocking episodes frequency in the Ural and Baikal is underestimated by most the 13 CMIP5 models, especially the short duration blocking episodes, and simulated superiorly in winter to in summer. However, modeled blocking episodes frequency is near to observed value in summer but overestimated in winter in Okhotsk. Model projections of instantaneous blocking frequency for the first half 21st century (2016-2065) shows that the RCP 4.5 projection yields a significant increasing frequency during January-May, decreasing frequency during June-August, and a little increasing frequency during September- December. The RCP 8.5 projection presents similar case to RCP 4.5 projection, but indicating more remarkable decreasing trend. Blocking episodes frequency of the multi-model ensemble mean obviously decreases in the Ural and Baikal (especially blocking episodes with short duration) and increase a little in Okhotsk in the first half 21st century. For blocking episodes with long duration

  18. The giant Jiaodong gold province: The key to a unified model for orogenic gold deposits?

    Directory of Open Access Journals (Sweden)

    David I. Groves

    2016-05-01

    Full Text Available Although the term orogenic gold deposit has been widely accepted for all gold-only lode-gold deposits, with the exception of Carlin-type deposits and rare intrusion-related gold systems, there has been continuing debate on their genesis. Early syngenetic models and hydrothermal models dominated by meteoric fluids are now clearly unacceptable. Magmatic-hydrothermal models fail to explain the genesis of orogenic gold deposits because of the lack of consistent spatially – associated granitic intrusions and inconsistent temporal relationships. The most plausible, and widely accepted, models involve metamorphic fluids, but the source of these fluids is hotly debated. Sources within deeper segments of the supracrustal successions hosting the deposits, the underlying continental crust, and subducted oceanic lithosphere and its overlying sediment wedge all have their proponents. The orogenic gold deposits of the giant Jiaodong gold province of China, in the delaminated North China Craton, contain ca. 120 Ma gold deposits in Precambrian crust that was metamorphosed over 2000 million years prior to gold mineralization. The only realistic source of fluid and gold is a subducted oceanic slab with its overlying sulfide-rich sedimentary package, or the associated mantle wedge. This could be viewed as an exception to a general metamorphic model where orogenic gold has been derived during greenschist- to amphibolite-facies metamorphism of supracrustal rocks: basaltic rocks in the Precambrian and sedimentary rocks in the Phanerozoic. Alternatively, if a holistic view is taken, Jiaodong can be considered the key orogenic gold province for a unified model in which gold is derived from late-orogenic metamorphic devolatilization of stalled subduction slabs and oceanic sediments throughout Earth history. The latter model satisfies all geological, geochronological, isotopic and geochemical constraints but the precise mechanisms of auriferous fluid release, like many

  19. The giant Jiaodong gold province:The key to a unified model for orogenic gold deposits?

    Institute of Scientific and Technical Information of China (English)

    David I. Groves; M. Santosh

    2016-01-01

    Although the term orogenic gold deposit has been widely accepted for all gold-only lode-gold deposits, with the exception of Carlin-type deposits and rare intrusion-related gold systems, there has been continuing debate on their genesis. Early syngenetic models and hydrothermal models dominated by meteoric fluids are now clearly unacceptable. Magmatic-hydrothermal models fail to explain the genesis of orogenic gold deposits because of the lack of consistent spatially e associated granitic intrusions and inconsistent temporal relationships. The most plausible, and widely accepted, models involve meta-morphic fluids, but the source of these fluids is hotly debated. Sources within deeper segments of the supracrustal successions hosting the deposits, the underlying continental crust, and subducted oceanic lithosphere and its overlying sediment wedge all have their proponents. The orogenic gold deposits of the giant Jiaodong gold province of China, in the delaminated North China Craton, contain ca. 120 Ma gold deposits in Precambrian crust that was metamorphosed over 2000 million years prior to gold mineralization. The only realistic source of fluid and gold is a subducted oceanic slab with its overlying sulfide-rich sedimentary package, or the associated mantle wedge. This could be viewed as an exception to a general metamorphic model where orogenic gold has been derived during greenschist- to amphibolite-facies metamorphism of supracrustal rocks: basaltic rocks in the Precambrian and sedi-mentary rocks in the Phanerozoic. Alternatively, if a holistic view is taken, Jiaodong can be considered the key orogenic gold province for a unified model in which gold is derived from late-orogenic metamorphic devolatilization of stalled subduction slabs and oceanic sediments throughout Earth history. The latter model satisfies all geological, geochronological, isotopic and geochemical constraints but the precise mechanisms of auriferous fluid release, like many other subduction

  20. Choosing preclinical study models of diabetic retinopathy: key problems for consideration

    Directory of Open Access Journals (Sweden)

    Mi XS

    2014-11-01

    Full Text Available Xue-Song Mi,1,2 Ti-Fei Yuan,3,4 Yong Ding,1 Jing-Xiang Zhong,1 Kwok-Fai So4,5 1Department of Ophthalmology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Psychology, Nanjing Normal University, Nanjing, People’s Republic of China; 4Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; 5Guangdong-Hongkong-Macau Institute of Central Nervous System, Jinan University, Guangzhou, People’s Republic of China Abstract: Diabetic retinopathy (DR is the most common complication of diabetes mellitus in the eye. Although the clinical treatment for DR has already developed to a relative high level, there are still many urgent problems that need to be investigated in clinical and basic science. Currently, many in vivo animal models and in vitro culture systems have been applied to solve these problems. Many approaches have also been used to establish different DR models. However, till now, there has not been a single study model that can clearly and exactly mimic the developmental process of the human DR. Choosing the suitable model is important, not only for achieving our research goals smoothly, but also, to better match with different experimental proposals in the study. In this review, key problems for consideration in choosing study models of DR are discussed. These problems relate to clinical relevance, different approaches for establishing models, and choice of different species of animals as well as of the specific in vitro culture systems. Attending to these considerations will deepen the understanding on current study models and optimize the experimental design for the final goal of preventing DR. Keywords: animal model, in vitro culture, ex vivo culture, neurovascular dysfunction

  1. P53 and MITF/Bcl-2 identified as key pathways in the acquired resistance of NRAS-mutant melanoma to MEK inhibition.

    Science.gov (United States)

    Najem, Ahmad; Krayem, Mohammad; Salès, François; Hussein, Nader; Badran, Bassam; Robert, Caroline; Awada, Ahmad; Journe, Fabrice; Ghanem, Ghanem E

    2017-09-01

    MEK inhibition to induce massive apoptosis in NRAS-mutant melanoma cells with wild-type or mutant p53. Hence, our data identify MITF/Bcl-2 as a key mechanism underlying resistance of NRAS-mutant melanoma cells to apoptosis by MEK inhibitors and paves the way for a promising drug combination that could prevent or reverse anti-MEK resistance in this group of patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Using analytic hierarchy process to identify the nurses with high stress-coping capability: model and application.

    Science.gov (United States)

    F C Pan, Frank

    2014-03-01

    Nurses have long been relied as the major labor force in hospitals. Featured with complicated and highly labor-intensive job requirement, multiple pressures from different sources was inevitable. Success in identifying stresses and accordingly coping with such stresses is important for job performance of nurses, and service quality of a hospital. Purpose of this research is to identify the determinants of nurses' capabilities. A modified Analytic Hierarchy Process (AHP) was adopted. Overall, 105 nurses from several randomly selected hospitals in southern Taiwan were investigated to generate factors. Ten experienced practitioners were included as the expert in the AHP to produce weights of each criterion. Six nurses from two regional hospitals were then selected to test the model. Four factors are then identified as the second level of hierarchy. The study result shows that the family factor is the most important factor, and followed by the personal attributes. Top three sub-criteria that attribute to the nurse's stress-coping capability are children's education, good career plan, and healthy family. The practical simulation provided evidence for the usefulness of this model. The study suggested including these key determinants into the practice of human-resource management, and restructuring the hospital's organization, creating an employee-support system as well as a family-friendly working climate. The research provided evidence that supports the usefulness of AHP in identifying the key factors that help stabilizing a nursing team.

  3. Using analytic hierarchy process to identify the nurses with high stress-coping capability: model and application.

    Directory of Open Access Journals (Sweden)

    Frank F C Pan

    2014-03-01

    Full Text Available Nurses have long been relied as the major labor force in hospitals. Featured with complicated and highly labor-intensive job requirement, multiple pressures from different sources was inevitable. Success in identifying stresses and accordingly coping with such stresses is important for job performance of nurses, and service quality of a hospital. Purpose of this research is to identify the determinants of nurses' capabilities.A modified Analytic Hierarchy Process (AHP was adopted. Overall, 105 nurses from several randomly selected hospitals in southern Taiwan were investigated to generate factors. Ten experienced practitioners were included as the expert in the AHP to produce weights of each criterion. Six nurses from two regional hospitals were then selected to test the model.Four factors are then identified as the second level of hierarchy. The study result shows that the family factor is the most important factor, and followed by the personal attributes. Top three sub-criteria that attribute to the nurse's stress-coping capability are children's education, good career plan, and healthy family. The practical simulation provided evidence for the usefulness of this model.The study suggested including these key determinants into the practice of human-resource management, and restructuring the hospital's organization, creating an employee-support system as well as a family-friendly working climate. The research provided evidence that supports the usefulness of AHP in identifying the key factors that help stabilizing a nursing team.

  4. Identifying Staff Development Needs of Cooperative Extension Faculty Using a Modified Borich Needs Assessment Model.

    Science.gov (United States)

    Waters, Randol G.; Haskell, Larry J.

    1989-01-01

    To identify staff development needs and test the Borich Needs Assessment Model, 68 faculty in Nevada were surveyed (90 percent response). Use of the model made rankings of individual topics substantively different from results obtained by traditional methods. (JOW)

  5. Transgenic mouse models resistant to diet-induced metabolic disease: is energy balance the key?

    Science.gov (United States)

    Gilliam, Laura A A; Neufer, P Darrell

    2012-09-01

    The prevalence and economic burden of obesity and type 2 diabetes is a driving force for the discovery of molecular targets to improve insulin sensitivity and glycemic control. Here, we review several transgenic mouse models that identify promising targets, ranging from proteins involved in the insulin signaling pathway, alterations of genes affecting energy metabolism, and transcriptional metabolic regulators. Despite the diverse endpoints in each model, a common thread that emerges is the necessity for maintenance of energy balance, suggesting pharmacotherapy must target the development of drugs that decrease energy intake, accelerate energy expenditure in a well controlled manner, or augment natural compensatory responses to positive energy balance.

  6. Key Elements of the User-Friendly, GFDL SKYHI General Circulation Model

    Directory of Open Access Journals (Sweden)

    Richard S. Hemler

    2000-01-01

    Full Text Available Over the past seven years, the portability of the GFDL SKYHI general circulation model has greatly increased. Modifications to the source code have allowed SKYHI to be run on the GFDL Cray Research PVP machines, the TMC CM-5 machine at Los Alamos National Laboratory, and more recently on the GFDL 40-processor Cray Research T3E system. At the same time, changes have been made to the model to make it more usable and flexible. Because of the reduction of the human resources available to manage and analyze scientific experiments, it is no longer acceptable to consider only the optimization of computer resources when producing a research code; one must also consider the availability and cost of the people necessary to maintain, modify and use the model as an investigative tool, and include these factors in defining the form of the model code. The new SKYHI model attempts to strike a balance between the optimization of the use of machine resources (CPU time, memory, disc and the optimal use of human resources (ability to understand code, ability to modify code, ability to perturb code to do experiments, ability to run code on different platforms. Two of the key features that make the new SKYHI code more usable and flexible are the archiving package and the user variable block. The archiving package is used to manage the writing of all archive files, which contain data for later analysis. The model-supplied user variable block allows the easy inclusion of any new variables needed for particular experiments.

  7. Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

    Science.gov (United States)

    Silva, M M; Lemos, J M; Coito, A; Costa, B A; Wigren, T; Mendonça, T

    2014-01-01

    This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used.

  8. A Clinical model to identify patients with high-risk coronary artery disease

    NARCIS (Netherlands)

    Y. Yang (Yelin); L. Chen (Li); Y. Yam (Yeung); S. Achenbach (Stephan); M. Al-Mallah (Mouaz); D.S. Berman (Daniel); M.J. Budoff (Matthew); F. Cademartiri (Filippo); T.Q. Callister (Tracy); H.-J. Chang (Hyuk-Jae); V.Y. Cheng (Victor); K. Chinnaiyan (Kavitha); R.C. Cury (Ricardo); A. Delago (Augustin); A. Dunning (Allison); G.M. Feuchtner (Gudrun); M. Hadamitzky (Martin); J. Hausleiter (Jörg); R.P. Karlsberg (Ronald); P.A. Kaufmann (Philipp); Y.-J. Kim (Yong-Jin); J. Leipsic (Jonathon); T.M. LaBounty (Troy); F.Y. Lin (Fay); E. Maffei (Erica); G.L. Raff (Gilbert); L.J. Shaw (Leslee); T.C. Villines (Todd); J.K. Min (James K.); B.J.W. Chow (Benjamin)

    2015-01-01

    textabstractObjectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify th

  9. A Clinical model to identify patients with high-risk coronary artery disease

    NARCIS (Netherlands)

    Y. Yang (Yelin); L. Chen (Li); Y. Yam (Yeung); S. Achenbach (Stephan); M. Al-Mallah (Mouaz); D.S. Berman (Daniel); M.J. Budoff (Matthew); F. Cademartiri (Filippo); T.Q. Callister (Tracy); H.-J. Chang (Hyuk-Jae); V.Y. Cheng (Victor); K. Chinnaiyan (Kavitha); R.C. Cury (Ricardo); A. Delago (Augustin); A. Dunning (Allison); G.M. Feuchtner (Gudrun); M. Hadamitzky (Martin); J. Hausleiter (Jörg); R.P. Karlsberg (Ronald); P.A. Kaufmann (Philipp); Y.-J. Kim (Yong-Jin); J. Leipsic (Jonathon); T.M. LaBounty (Troy); F.Y. Lin (Fay); E. Maffei (Erica); G.L. Raff (Gilbert); L.J. Shaw (Leslee); T.C. Villines (Todd); J.K. Min (James K.); B.J.W. Chow (Benjamin)

    2015-01-01

    textabstractObjectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify th

  10. Structural identifiability of a model for the acetic acid fermentation process.

    Science.gov (United States)

    Jiménez-Hornero, Jorge E; Santos-Dueñas, Inés M; Garci A-Garci A, Isidoro

    2008-12-01

    Modelling has proved an essential tool for addressing research into biotechnological processes, particularly with a view to their optimization and control. Parameter estimation via optimization approaches is among the major steps in the development of biotechnology models. In fact, one of the first tasks in the development process is to determine whether the parameters concerned can be unambiguously determined and provide meaningful physical conclusions as a result. The analysis process is known as 'identifiability' and presents two different aspects: structural or theoretical identifiability and practical identifiability. While structural identifiability is concerned with model structure alone, practical identifiability takes into account both the quantity and quality of experimental data. In this work, we discuss the theoretical identifiability of a new model for the acetic acid fermentation process and review existing methods for this purpose.

  11. A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice, key challenges, and recommendations for the future.

    Science.gov (United States)

    Critchlow, Simone; Hirst, Matthew; Akehurst, Ron; Phillips, Ceri; Philips, Zoe; Sullivan, Will; Dunlop, Will C N

    2017-02-01

    Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain. The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines. The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled. To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform

  12. The undecided have the key: Interaction-driven opinion dynamics in a three state model

    CERN Document Server

    Balenzuela, Pablo; Semeshenko, Viktoriya

    2015-01-01

    The effects of interpersonal interactions on individual's agreements result in a social aggregation process which is reflected in the formation of collective states, as for instance, groups of individuals with a similar opinion about a given issue. This field, which has been a longstanding concern of sociologists and psychologists, has been extended into an area of experimental social psychology, and even has attracted the attention of physicists and mathematicians. In this article, we present a novel model of opinion formation in which agents may either have a strict preference for a choice, or be undecided. The opinion shift emerges during interpersonal communications, as a consequence of a cumulative process of conviction for one of the two extremes opinions through repeated interactions. There are two main ingredients which play key roles in determining the steady state: the initial fraction of undecided agents and the conviction's sensitivity in each interaction. As a function of these two parameters, th...

  13. Operational Details of the Five Domains Model and Its Key Applications to the Assessment and Management of Animal Welfare

    Science.gov (United States)

    Mellor, David J.

    2017-01-01

    Simple Summary The Five Domains Model is a focusing device to facilitate systematic, structured, comprehensive and coherent assessment of animal welfare; it is not a definition of animal welfare, nor is it intended to be an accurate representation of body structure and function. The purpose of each of the five domains is to draw attention to areas that are relevant to both animal welfare assessment and management. This paper begins by briefly describing the major features of the Model and the operational interactions between the five domains, and then it details seven interacting applications of the Model. These underlie its utility and increasing application to welfare assessment and management in diverse animal use sectors. Abstract In accord with contemporary animal welfare science understanding, the Five Domains Model has a significant focus on subjective experiences, known as affects, which collectively contribute to an animal’s overall welfare state. Operationally, the focus of the Model is on the presence or absence of various internal physical/functional states and external circumstances that give rise to welfare-relevant negative and/or positive mental experiences, i.e., affects. The internal states and external circumstances of animals are evaluated systematically by referring to each of the first four domains of the Model, designated “Nutrition”, “Environment”, “Health” and “Behaviour”. Then affects, considered carefully and cautiously to be generated by factors in these domains, are accumulated into the fifth domain, designated “Mental State”. The scientific foundations of this operational procedure, published in detail elsewhere, are described briefly here, and then seven key ways the Model may be applied to the assessment and management of animal welfare are considered. These applications have the following beneficial objectives—they (1) specify key general foci for animal welfare management; (2) highlight the foundations of

  14. Systemic Thinking and Requisite Holism in Mastering Logistics Risks: the Model for Identifying Risks in Organisations and Supply Chain

    Directory of Open Access Journals (Sweden)

    Bojan Rosi

    2013-02-01

    Full Text Available Risks in logistic processes represent one of the major issues in supply chain management nowadays. Every organization strives for success, and uninterrupted operations are the key factors in achieving this goal, which cannot be achieved without efficient risk management. In the scope of supply chain risk research, we identified some key issues in the field, the major issue being the lack of standardization and models, which can make risk management in an organization easier and more efficient. Consequently, we developed a model, which captures and identifies risks in an organization and its supply chain. It is in accordance with the general risk management standard – ISO 31000, and incorporates some relevant recent findings from general and supply chain risk management, especially from the viewpoint of public segmentation. This experimental catalogue (which is also published online can serve as a checklist and a starting point of supply chain risk management in organizations. Its main idea is cooperation between experts from the area in order to compile an ever-growing list of possible risks and to provide an insight in the model and its value in practice, for which reason input and opinions of anyone who uses our model are greatly appreciated and included in the catalogue.

  15. Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

    Science.gov (United States)

    Marín-Menéndez, Alejandro; Montis, Costanza; Díaz-Calvo, Teresa; Carta, Davide; Hatzixanthis, Kostas; Morris, Christopher J.; McArthur, Michael; Berti, Debora

    2017-01-01

    Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy.

  16. Characterization of a Field Spectroradiometer for Unattended Vegetation Monitoring. Key Sensor Models and Impacts on Reflectance

    Directory of Open Access Journals (Sweden)

    Javier Pacheco-Labrador

    2015-02-01

    Full Text Available Field spectroradiometers integrated in automated systems at Eddy Covariance (EC sites are a powerful tool for monitoring and upscaling vegetation physiology and carbon and water fluxes. However, exposure to varying environmental conditions can affect the functioning of these sensors, especially if these cannot be completely insulated and stabilized. This can cause inaccuracy in the spectral measurements and hinder the comparison between data acquired at different sites. This paper describes the characterization of key sensor models in a double beam spectroradiometer necessary to calculate the Hemispherical-Conical Reflectance Factor (HCRF. Dark current, temperature dependence, non-linearity, spectral calibration and cosine receptor directional responses are modeled in the laboratory as a function of temperature, instrument settings, radiation measured or illumination angle. These models are used to correct the spectral measurements acquired continuously by the same instrument integrated outdoors in an automated system (AMSPEC-MED. Results suggest that part of the instrumental issues cancel out mutually or can be controlled by the instrument configuration, so that changes induced in HCFR reached about 0.05 at maximum. However, these corrections are necessary to ensure the inter-comparison of data with other ground or remote sensors and to discriminate instrumentally induced changes in HCRF from those related with vegetation physiology and directional effects.

  17. A study of key features of random atmospheric disturbance models for the approach flight phase

    Science.gov (United States)

    Heffley, R. K.

    1977-01-01

    An analysis and brief simulator experiment were performed to identify and classify important features of random turbulence for the landing approach flight phase. The analysis of various wind models was carried out within the context of the longitudinal closed-loop pilot/vehicle system. The analysis demonstrated the relative importance of atmospheric disturbance scale lengths, horizontal versus vertical gust components, decreasing altitude, and spectral forms of disturbances versus the pilot/vehicle system. Among certain competing wind models, the analysis predicted no significant difference in pilot performance. This was confirmed by a moving base simulator experiment which evaluated the two most extreme models. A number of conclusions were reached: attitude constrained equations do provide a simple but effective approach to describing the closed-loop pilot/vehicle. At low altitudes the horizontal gust component dominates pilot/vehicle performance.

  18. Assessing Reliability of Cellulose Hydrolysis Models to Support Biofuel Process Design – Identifiability and Uncertainty Analysis

    DEFF Research Database (Denmark)

    Sin, Gürkan; Meyer, Anne S.; Gernaey, Krist

    2010-01-01

    The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done...... are not informative enough (sensitivities of 16 parameters were insignificant). This indicates that the NREL model has severe parameter uncertainty, likely to be the case for other hydrolysis models as well since similar kinetic expressions are used. To overcome this impasse, we have used the Monte Carlo procedure...

  19. Simple dynamical models capturing the key features of the Central Pacific El Niño.

    Science.gov (United States)

    Chen, Nan; Majda, Andrew J

    2016-10-18

    The Central Pacific El Niño (CP El Niño) has been frequently observed in recent decades. The phenomenon is characterized by an anomalous warm sea surface temperature (SST) confined to the central Pacific and has different teleconnections from the traditional El Niño. Here, simple models are developed and shown to capture the key mechanisms of the CP El Niño. The starting model involves coupled atmosphere-ocean processes that are deterministic, linear, and stable. Then, systematic strategies are developed for incorporating several major mechanisms of the CP El Niño into the coupled system. First, simple nonlinear zonal advection with no ad hoc parameterization of the background SST gradient is introduced that creates coupled nonlinear advective modes of the SST. Secondly, due to the recent multidecadal strengthening of the easterly trade wind, a stochastic parameterization of the wind bursts including a mean easterly trade wind anomaly is coupled to the simple atmosphere-ocean processes. Effective stochastic noise in the wind burst model facilitates the intermittent occurrence of the CP El Niño with realistic amplitude and duration. In addition to the anomalous warm SST in the central Pacific, other major features of the CP El Niño such as the rising branch of the anomalous Walker circulation being shifted to the central Pacific and the eastern Pacific cooling with a shallow thermocline are all captured by this simple coupled model. Importantly, the coupled model succeeds in simulating a series of CP El Niño that lasts for 5 y, which resembles the two CP El Niño episodes during 1990-1995 and 2002-2006.

  20. Keys to the House: Unlocking Residential Savings With Program Models for Home Energy Upgrades

    Energy Technology Data Exchange (ETDEWEB)

    Grevatt, Jim [Energy Futures Group (United States); Hoffman, Ian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Hoffmeyer, Dale [US Department of Energy, Washington, DC (United States)

    2017-07-05

    After more than 40 years of effort, energy efficiency program administrators and associated contractors still find it challenging to penetrate the home retrofit market, especially at levels commensurate with state and federal goals for energy savings and emissions reductions. Residential retrofit programs further have not coalesced around a reliably successful model. They still vary in design, implementation and performance, and they remain among the more difficult and costly options for acquiring savings in the residential sector. If programs are to contribute fully to meeting resource and policy objectives, administrators need to understand what program elements are key to acquiring residential savings as cost effectively as possible. To that end, the U.S. Department of Energy (DOE) sponsored a comprehensive review and analysis of home energy upgrade programs with proven track records, focusing on those with robustly verified savings and constituting good examples for replication. The study team reviewed evaluations for the period 2010 to 2014 for 134 programs that are funded by customers of investor-owned utilities. All are programs that promote multi-measure retrofits or major system upgrades. We paid particular attention to useful design and implementation features, costs, and savings for nearly 30 programs with rigorous evaluations of performance. This meta-analysis describes program models and implementation strategies for (1) direct install retrofits; (2) heating, ventilating and air-conditioning (HVAC) replacement and early retirement; and (3) comprehensive, whole-home retrofits. We analyze costs and impacts of these program models, in terms of both energy savings and emissions avoided. These program models can be useful guides as states consider expanding their strategies for acquiring energy savings as a resource and for emissions reductions. We also discuss the challenges of using evaluations to create program models that can be confidently applied in

  1. Testing Models: A Key Aspect to Promote Teaching Activities Related to Models and Modelling in Biology Lessons?

    Science.gov (United States)

    Krell, Moritz; Krüger, Dirk

    2016-01-01

    This study investigated biology teachers' (N = 148) understanding of models and modelling (MoMo), their model-related teaching activities and relations between the two. A framework which distinguishes five aspects of MoMo in science ("nature of models," "multiple models," "purpose of models," "testing…

  2. Testing Models: A Key Aspect to Promote Teaching Activities Related to Models and Modelling in Biology Lessons?

    Science.gov (United States)

    Krell, Moritz; Krüger, Dirk

    2016-01-01

    This study investigated biology teachers' (N = 148) understanding of models and modelling (MoMo), their model-related teaching activities and relations between the two. A framework which distinguishes five aspects of MoMo in science ("nature of models," "multiple models," "purpose of models," "testing…

  3. Key Characteristics of Combined Accident including TLOFW accident for PSA Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bo Gyung; Kang, Hyun Gook [KAIST, Daejeon (Korea, Republic of); Yoon, Ho Joon [Khalifa University of Science, Technology and Research, Abu Dhabi (United Arab Emirates)

    2015-05-15

    The conventional PSA techniques cannot adequately evaluate all events. The conventional PSA models usually focus on single internal events such as DBAs, the external hazards such as fire, seismic. However, the Fukushima accident of Japan in 2011 reveals that very rare event is necessary to be considered in the PSA model to prevent the radioactive release to environment caused by poor treatment based on lack of the information, and to improve the emergency operation procedure. Especially, the results from PSA can be used to decision making for regulators. Moreover, designers can consider the weakness of plant safety based on the quantified results and understand accident sequence based on human actions and system availability. This study is for PSA modeling of combined accidents including total loss of feedwater (TLOFW) accident. The TLOFW accident is a representative accident involving the failure of cooling through secondary side. If the amount of heat transfer is not enough due to the failure of secondary side, the heat will be accumulated to the primary side by continuous core decay heat. Transients with loss of feedwater include total loss of feedwater accident, loss of condenser vacuum accident, and closure of all MSIVs. When residual heat removal by the secondary side is terminated, the safety injection into the RCS with direct primary depressurization would provide alternative heat removal. This operation is called feed and bleed (F and B) operation. Combined accidents including TLOFW accident are very rare event and partially considered in conventional PSA model. Since the necessity of F and B operation is related to plant conditions, the PSA modeling for combined accidents including TLOFW accident is necessary to identify the design and operational vulnerabilities.The PSA is significant to assess the risk of NPPs, and to identify the design and operational vulnerabilities. Even though the combined accident is very rare event, the consequence of combined

  4. Novel insights into CB1 cannabinoid receptor signaling: a key interaction identified between the extracellular-3 loop and transmembrane helix 2.

    Science.gov (United States)

    Marcu, Jahan; Shore, Derek M; Kapur, Ankur; Trznadel, Megan; Makriyannis, Alexandros; Reggio, Patricia H; Abood, Mary E

    2013-05-01

    Activation of the cannabinoid CB1 receptor (CB1) is modulated by aspartate residue D2.63(176) in transmembrane helix (TMH) 2. Interestingly, D2.63 does not affect the affinity for ligand binding at the CB1 receptor. Studies in class A G protein-coupled receptors have suggested an ionic interaction between residues of TMH2 and 7. In this report, modeling studies identified residue K373 in the extracellular-3 (EC-3) loop in charged interactions with D2.63. We investigated this possibility by performing reciprocal mutations and biochemical studies. D2.63(176)A, K373A, D2.63(176)A-K373A, and the reciprocal mutant with the interacting residues juxtaposed D2.63(176)K-K373D were characterized using radioligand binding and guanosine 5'-3-O-(thio)triphosphate functional assays. None of the mutations resulted in a significant change in the binding affinity of N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A) or (-)-3cis -[2-hydroxyl-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-[3-hydroxyl-propyl] cyclohexan-1-ol (CP55,940). Modeling studies indicated that binding-site interactions and energies of interaction for CP55,940 were similar between wild-type and mutant receptors. However, the signaling of CP55,940, and (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)-methanone mesylate (WIN55,212-2) was impaired at the D2.63(176)A-K373A and the single-alanine mutants. In contrast, the reciprocal D2.63(176)K-K373D mutant regained function for both CP55,940 and WIN55,212-2. Computational results indicate that the D2.63(176)-K373 ionic interaction strongly influences the conformation(s) of the EC-3 loop, providing a structure-based rationale for the importance of the EC-3 loop to signal transduction in CB1. The putative ionic interaction results in the EC-3 loop pulling over the top (extracellular side) of the receptor; this EC-3 loop conformation may serve

  5. Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

    Science.gov (United States)

    He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

    2014-12-01

    Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

  6. Identifiability of the Sign of Covariate Effects in the Competing Risks Model

    DEFF Research Database (Denmark)

    Lo, Simon M.S.; Wilke, Ralf

    2017-01-01

    We present a new framework for the identification of competing risks models, which also include Roy models. We show that by establishing a Hicksian-type decomposition, the direction of covariate effects on the marginal distributions of the competing risks model can be identified under weak...... of the range of durations for which the direction of the covariate effect is identified, particularly for long duration....

  7. Bayesian inference for partially identified models exploring the limits of limited data

    CERN Document Server

    Gustafson, Paul

    2015-01-01

    Introduction Identification What Is against Us? What Is for Us? Some Simple Examples of Partially Identified ModelsThe Road Ahead The Structure of Inference in Partially Identified Models Bayesian Inference The Structure of Posterior Distributions in PIMs Computational Strategies Strength of Bayesian Updating, Revisited Posterior MomentsCredible Intervals Evaluating the Worth of Inference Partial Identification versus Model Misspecification The Siren Call of Identification Comp

  8. MOLECULAR MODELLING OF HUMAN ALDEHYDE OXIDASE AND IDENTIFICATION OF THE KEY INTERACTIONS IN THE ENZYME-SUBSTRATE COMPLEX

    Directory of Open Access Journals (Sweden)

    Siavoush Dastmalchi

    2005-05-01

    Full Text Available Aldehyde oxidase (EC 1.2.3.1, a cytosolic enzyme containing FAD, molybdenum and iron-sulphur cluster, is a member of non-cytochrome P-450 enzymes called molybdenum hydroxylases which is involved in the metabolism of a wide range of endogenous compounds and many drug substances. Drug metabolism is one of the important characteristics which influences many aspects of a therapeutic agent such as routes of administration, drug interaction and toxicity and therefore, characterisation of the key interactions between enzymes and substrates is very important from drug development point of view. The aim of this study was to generate a three-dimensional model of human aldehyde oxidase (AO in order to assist us to identify the mode of interaction between enzyme and a set of phethalazine/quinazoline derivatives. Both sequence-based (BLAST and inverse protein fold recognition methods (THREADER were used to identify the crystal structure of bovine xanthine dehydrogenase (pdb code of 1FO4 as the suitable template for comparative modelling of human AO. Model structure was generated by aligning and then threading the sequence of human AO onto the template structure, incorporating the associated cofactors, and molecular dynamics simulations and energy minimization using GROMACS program. Different criteria which were measured by the PROCHECK, QPACK, VERIFY-3D were indicative of a proper fold for the predicted structural model of human AO. For example, 97.9 percentages of phi and psi angles were in the favoured and most favoured regions in the ramachandran plot, and all residues in the model are assigned environmentally positive compatibility scores. Further evaluation on the model quality was performed by investigation of AO-mediated oxidation of a set of phthalazine/quinazoline derivatives to develop QSAR model capable of describing the extent of the oxidation. Substrates were aligned by docking onto the active site of the enzyme using GOLD technology and then

  9. Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

    Science.gov (United States)

    Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

    2010-04-01

    Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

  10. Key strategies for predictive exploration in mature environment: model innovation, exploration technology optimization and information integration

    Institute of Scientific and Technical Information of China (English)

    LIU Liang-ming; PENG Sheng-lin

    2005-01-01

    Prediction has become more and more difficult in mineral exploration, especially in the mature exploration environment such as Tongling copper district. For enhancing predictive discovery of hidden ore deposits in such mature environment, the key strategies which should be adopted include the innovation of the exploration models, application of the advanced exploration techniques and integration of multiple sets of information. The innovation of the exploration models should incorporate the new metallogenic concepts that are based on the geodynamic anatomization. The advanced techniques applied in the mature exploration environment should aim at the speciality and complexity of the geological setting and working environments. The information synthesis is to integrate multiple sets of data for giving a more credible and visual prospectivity map by using the geographic imformation system(GIS) and several mathematical methods, such as weight of evidence and fuzzy logic, which can extract useful information from every set of data as much as possible. Guided by these strategies, a predictive exploration in Fenghuangshan ore field of Tongling copper district was implemented, and a hidden ore deposit was discovered.

  11. Combat-Related Heterotopic Ossification: Development of Animal Models for Identifying Mechanisms and Testing Therapeutics

    Science.gov (United States)

    2016-03-01

    etiology, treatment, and prevention is the absence of a reliable and reproducible small animal model that can be used to characterize combat‐related HO...contamination and subsequent wound colonization may be a key risk factor. Using a small animal model of blast-related extremity injury involving a...to the systemic and perhaps local antimicrobial therapies geared towards decreasing bioburden in combat wounds. 6 Using our blast-related HO

  12. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    Science.gov (United States)

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-11-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

  13. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

    Directory of Open Access Journals (Sweden)

    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  14. Identifying Ghanaian Pre-Service Teachers' Readiness for Computer Use: A Technology Acceptance Model Approach

    Science.gov (United States)

    Gyamfi, Stephen Adu

    2016-01-01

    This study extends the technology acceptance model to identify factors that influence technology acceptance among pre-service teachers in Ghana. Data from 380 usable questionnaires were tested against the research model. Utilising the extended technology acceptance model (TAM) as a research framework, the study found that: pre-service teachers'…

  15. Identifying E-Business Model:A Value Chain-Based Analysis

    Institute of Scientific and Technical Information of China (English)

    ZENG Qingfeng; HUANG Lihua

    2004-01-01

    E-business will change the ways that all companies do business, and most traditional businesses will evolve from their current business model to a combination of place and space via e-business model To choose the proper e-business model becomes the important strategic concern for company to succeed The main objective of this paper is to investigate the analysis framework for identifying e-business model Based on the e-business process, from the value chain to the value net perspective. This paper provides a theoretical framework for identifying e-business models, and results in 11 e-business models. The strategic intend of every e-business model is discussed in the end of this paper. An enterprise e-business model design and implementation can be specified by the combination of one or more among 11 e-business models.

  16. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  17. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  18. Local identifiability for two and three-compartment pharmacokinetic models with time-lags.

    Science.gov (United States)

    Merino, J A; De Biasi, J; Plusquellec, Y; Houin, G

    1998-06-01

    In this paper, we show that time-lags between compartments in a 2 and 3 compartment pharmacokinetic model may be taken into account but that separate identification for model parameters and for time-lags would not be suitable. Furthermore, it may happen that a time-lag model is locally identifiable while the corresponding model without delay is not. For two-compartment delayed models, with only one observation, it is not necessary to have two different inputs contrary to the case without time-lag. Both the Laplace transformation and a Jacobian matrix are used in an identifiability study. For all two-compartment models we have investigated which kind of parameters or lags are identifiable from amount (Q) or concentration (C) measures.

  19. A general model-based design of experiments approach to achieve practical identifiability of pharmacokinetic and pharmacodynamic models.

    Science.gov (United States)

    Galvanin, Federico; Ballan, Carlo C; Barolo, Massimiliano; Bezzo, Fabrizio

    2013-08-01

    The use of pharmacokinetic (PK) and pharmacodynamic (PD) models is a common and widespread practice in the preliminary stages of drug development. However, PK-PD models may be affected by structural identifiability issues intrinsically related to their mathematical formulation. A preliminary structural identifiability analysis is usually carried out to check if the set of model parameters can be uniquely determined from experimental observations under the ideal assumptions of noise-free data and no model uncertainty. However, even for structurally identifiable models, real-life experimental conditions and model uncertainty may strongly affect the practical possibility to estimate the model parameters in a statistically sound way. A systematic procedure coupling the numerical assessment of structural identifiability with advanced model-based design of experiments formulations is presented in this paper. The objective is to propose a general approach to design experiments in an optimal way, detecting a proper set of experimental settings that ensure the practical identifiability of PK-PD models. Two simulated case studies based on in vitro bacterial growth and killing models are presented to demonstrate the applicability and generality of the methodology to tackle model identifiability issues effectively, through the design of feasible and highly informative experiments.

  20. Clinical prediction model to identify vulnerable patients in ambulatory surgery: towards optimal medical decision-making

    NARCIS (Netherlands)

    H. Mijderwijk (Herjan); R.J. Stolker (Robert); H.J. Duivenvoorden (Hugo); M. Klimek (Markus); E.W. Steyerberg (Ewout)

    2016-01-01

    markdownabstract__Background:__ Ambulatory surgery patients are at risk of adverse psychological outcomes such as anxiety, aggression, fatigue, and depression. We developed and validated a clinical prediction model to identify patients who were vulnerable to these psychological outcome parameters.

  1. iPSC-Based Models to Unravel Key Pathogenetic Processes Underlying Motor Neuron Disease Development

    Directory of Open Access Journals (Sweden)

    Irene Faravelli

    2014-10-01

    Full Text Available Motor neuron diseases (MNDs are neuromuscular disorders affecting rather exclusively upper motor neurons (UMNs and/or lower motor neurons (LMNs. The clinical phenotype is characterized by muscular weakness and atrophy leading to paralysis and almost invariably death due to respiratory failure. Adult MNDs include sporadic and familial amyotrophic lateral sclerosis (sALS-fALS, while the most common infantile MND is represented by spinal muscular atrophy (SMA. No effective treatment is ccurrently available for MNDs, as for the vast majority of neurodegenerative disorders, and cures are limited to supportive care and symptom relief. The lack of a deep understanding of MND pathogenesis accounts for the difficulties in finding a cure, together with the scarcity of reliable in vitro models. Recent progresses in stem cell field, in particular in the generation of induced Pluripotent Stem Cells (iPSCs has made possible for the first time obtaining substantial amounts of human cells to recapitulate in vitro some of the key pathogenetic processes underlying MNDs. In the present review, recently published studies involving the use of iPSCs to unravel aspects of ALS and SMA pathogenesis are discussed with an overview of their implications in the process of finding a cure for these still orphan disorders.

  2. Modelling management process of key drivers for economic sustainability in the modern conditions of economic development

    Directory of Open Access Journals (Sweden)

    Pishchulina E.S.

    2017-01-01

    Full Text Available The text is about issues concerning the management of driver for manufacturing enterprise economic sustainability and manufacturing enterprise sustainability assessment as the key aspect of the management of enterprise economic sustainability. The given issues become topical as new requirements for the methods of manufacturing enterprise management in the modern conditions of market economy occur. An economic sustainability model that is considered in the article is an integration of enterprise economic growth, economic balance of external and internal environment and economic sustainability. The method of assessment of economic sustainability of a manufacturing enterprise proposed in the study allows to reveal some weaknesses in the enterprise performance, and untapped reserves, which can be further used to improve the economic sustainability and efficiency of the enterprise. The management of manufacturing enterprise economic sustainability is one of the most important factors of business functioning and development in modern market economy. The relevance of this trend is increasing in accordance with the objective requirements of the growing volumes of production and sale, the increasing complexity of economic relations, changing external environment of an enterprise.

  3. Precision tests of the Standard Model using key observables of $CP$ violation and rare decays

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00346274; Albrecht, Johannes

    In this thesis advanced statistical methods are used for precision studies in the flavour sector of the Standard Model of particle physics. The necessary tools are developed and applied to two key measurements of the LHCb experiment: the determination of the CKM angle $\\gamma$ and the search for rare $B^{0} _{s} \\to \\mu^+ \\mu^-$ and $B^0 \\to \\mu^+ \\mu^-$ decays. The CKM angle $\\gamma$ is, for the first time, measured from $B^0 _s \\to D^\\mp _s K^\\pm$ decays using a dataset corresponding to $1\\,\\mathrm{fb}^{-1}$ of $pp$ interactions at a centre-of-mass energy of $\\sqrt{s} = 7\\mathrm{TeV}$. The result of $\\gamma = (115^{+27}_{-43})^{\\circ}$ is then combined with a set of $\\gamma$ measurements in ${B} \\to Dh$ decays resulting in a precision on $\\gamma$ of $<8^{\\circ}$. This result improves the legacy results from the $B$-factories by more than a factor of two. The rare decays $B^{0} _{s} \\to \\mu^+ \\mu^-$ and $B^0 \\to \\mu^+ \\mu^-$ are analysed on a dataset corresponding to $3\\,\\mathrm{fb}^{-1}$ of $pp$ interac...

  4. Imbalanced Insulin Actions in Obesity and Type 2 Diabetes: Key Mouse Models of Insulin Signaling Pathway.

    Science.gov (United States)

    Kubota, Tetsuya; Kubota, Naoto; Kadowaki, Takashi

    2017-04-04

    Since the discovery of the tyrosine kinase activity of the insulin receptor (IR), researchers have been engaged in intensive efforts to resolve physiological functions of IR and its major downstream targets, insulin receptor substrate 1 (Irs1) and Irs2. Studies conducted using systemic and tissue-specific gene-knockout mice of IR, Irs1, and Irs2 have revealed the physiological roles of these molecules in each tissue and interactions among multiple tissues. In obesity and type 2 diabetes, selective downregulation of Irs2 and its downstream actions to cause reduced insulin actions was associated with increased insulin actions through Irs1 in variety tissues. Thus, we propose the novel concept of "organ- and pathway-specific imbalanced insulin action" in obesity and type 2 diabetes, which includes and extends "selective insulin resistance." This Review focuses on recent progress in understanding insulin signaling and insulin resistance using key mouse models for elucidating pathophysiology of human obesity and type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A parameter estimation and identifiability analysis methodology applied to a street canyon air pollution model

    DEFF Research Database (Denmark)

    Ottosen, Thor Bjørn; Ketzel, Matthias; Skov, Henrik

    2016-01-01

    Pollution Model (OSPM®). To assess the predictive validity of the model, the data is split into an estimation and a prediction data set using two data splitting approaches and data preparation techniques (clustering and outlier detection) are analysed. The sensitivity analysis, being part......Mathematical models are increasingly used in environmental science thus increasing the importance of uncertainty and sensitivity analyses. In the present study, an iterative parameter estimation and identifiability analysis methodology is applied to an atmospheric model – the Operational Street...

  6. A New Method for Identifying the Model Error of Adjustment System

    Institute of Scientific and Technical Information of China (English)

    TAO Benzao; ZHANG Chaoyu

    2005-01-01

    Some theory problems affecting parameter estimation are discussed in this paper. Influence and transformation between errors of stochastic and functional models is pointed out as well. For choosing the best adjustment model, a formula, which is different from the literatures existing methods, for estimating and identifying the model error, is proposed. On the basis of the proposed formula, an effective approach of selecting the best model of adjustment system is given.

  7. A Hybrid Network Model to Extract Key Criteria and Its Application for Brand Equity Evaluation

    Directory of Open Access Journals (Sweden)

    Chin-Yi Chen

    2012-01-01

    Full Text Available Making a decision implies that there are alternative choices to be considered, and a major challenge of decision-making is to identify the adequate criteria for program planning or problem evaluation. The decision-makers’ criteria consists of the characteristics or requirements each alternative must possess and the alternatives are rated on how well they possess each criterion. We often use criteria developed and used by different researchers and institutions, and these criteria have similar means and can be substituted for one another. Choosing from existing criteria offers a practical method to engineers hoping to derive a set of criteria for evaluating objects or programs. We have developed a hybrid model for extracting evaluation criteria which considers substitutions between the criteria. The model is developed based on Social Network Analysis and Maximum Mean De-Entropy algorithms. In this paper, the introduced methodology will also be applied to analyze the criteria for assessing brand equity as an application example. The proposed model demonstrates that it is useful in planning feasibility criteria and has applications in other evaluation-planning purposes.

  8. Model of the Students' Key Competences Development through Interactive Whiteboard in the Subject of Technology

    Science.gov (United States)

    Brecka, Peter; Valentová, Monika

    2017-01-01

    The basis of the submitted study are the continuously rising demands to alter the curricula with the aim to develop students' key competences in order to increase their professional versatility. The lack of scientific research and discussions show that little investigation has been done on the issue of development of key competences. Therefore,…

  9. Identifiability of parameters and behaviour of MCMC chains: a case study using the reaction norm model.

    Science.gov (United States)

    Shariati, M M; Korsgaard, I R; Sorensen, D

    2009-04-01

    Markov chain Monte Carlo (MCMC) enables fitting complex hierarchical models that may adequately reflect the process of data generation. Some of these models may contain more parameters than can be uniquely inferred from the distribution of the data, causing non-identifiability. The reaction norm model with unknown covariates (RNUC) is a model in which unknown environmental effects can be inferred jointly with the remaining parameters. The problem of identifiability of parameters at the level of the likelihood and the associated behaviour of MCMC chains were discussed using the RNUC as an example. It was shown theoretically that when environmental effects (covariates) are considered as random effects, estimable functions of the fixed effects, (co)variance components and genetic effects are identifiable as well as the environmental effects. When the environmental effects are treated as fixed and there are other fixed factors in the model, the contrasts involving environmental effects, the variance of environmental sensitivities (genetic slopes) and the residual variance are the only identifiable parameters. These different identifiability scenarios were generated by changing the formulation of the model and the structure of the data and the models were then implemented via MCMC. The output of MCMC sampling schemes was interpreted in the light of the theoretical findings. The erratic behaviour of the MCMC chains was shown to be associated with identifiability problems in the likelihood, despite propriety of posterior distributions, achieved by arbitrarily chosen uniform (bounded) priors. In some cases, very long chains were needed before the pattern of behaviour of the chain may signal the existence of problems. The paper serves as a warning concerning the implementation of complex models where identifiability problems can be difficult to detect a priori. We conclude that it would be good practice to experiment with a proposed model and to understand its features

  10. A Study of the Key Elements in the Jerome Model, the Horace Model and the Schleiermacher Model

    Institute of Scientific and Technical Information of China (English)

    都潇潇

    2016-01-01

    There are Two very popular and important translation models, namely the Jerome Model, the Horace Model , which can be thought to be the forerunner of the translation theory nowadays. They share one common concept—faithfulness. the Two models are discussed one by one to aim at pointing out the main differences and similarities, from which we can learn more and do better translation in our studies and works. Finally, the paper draws a conclusion that no single translation model is really better than another because the criteria of translation are dynamic rather than static.

  11. Identifying key domains of health-related quality of life for patients with chronic obstructive pulmonary disease: interviews with healthcare professionals

    NARCIS (Netherlands)

    Paap, M.C.S.; Bode, C.; Lenferink, Lonneke I.M.; Terwee, Caroline B.; Palen, van der J.A.M.

    2015-01-01

    Purpose The aim of this paper is to identify which domains of health-related quality of life (HRQoL) are most important for patients with chronic obstructive pulmonary disease (COPD), from the perspective of healthcare professionals (HCPs). Methods Thirteen Dutch HCPs [six pulmonologists, three

  12. Identifying key domains of health-related quality of life for patients with chronic obstructive pulmonary disease : interviews with healthcare professionals

    NARCIS (Netherlands)

    Paap, Muirne C S; Bode, Christina; Lenferink, Lonneke I M; Terwee, Caroline B; van der Palen, Job

    2015-01-01

    PURPOSE: The aim of this paper is to identify which domains of health-related quality of life (HRQoL) are most important for patients with chronic obstructive pulmonary disease (COPD), from the perspective of healthcare professionals (HCPs). METHODS: Thirteen Dutch HCPs [six pulmonologists, three pu

  13. Identifying and Supporting English Learner Students with Learning Disabilities: Key Issues in the Literature and State Practice. REL 2015-086

    Science.gov (United States)

    Burr, Elizabeth; Haas, Eric; Ferriere, Karen

    2015-01-01

    While the literature on learning disabilities and on second-language acquisition is relatively extensive within the field of education, less is known about the specific characteristics and representation of English learner students with learning disabilities. Because there are no definitive resources and processes for identifying and determining…

  14. Discrete Methods Based on First Order Reversal Curves to Identify Preisach Model of Smart Materials

    Institute of Scientific and Technical Information of China (English)

    LI Fan; ZHAO Jian-hui

    2007-01-01

    Preisach model is widely used in modeling of smart materials. Although first order reversal curves (FORCs) have often found applications in the fields of physics and geology, they are able to serve to identify Preisach model. In order to clarify the relationship between the Preisach model and the first order reversal curves, this paper is directed towards: (1) giving the reason a first order reversal curve is introduced; (2) presenting, for identifying Preisach model, two discrete methods, which are analytically based on first order reversal curves. Herein also is indicated the solution's uniqueness of these two identifying methods. At last, the validity of these two methods is verified by simulating a real smart actuator both methods have been applied to.

  15. Ogyges Kaup, a flightless genus of Passalidae (Coleoptera) from Mesoamerica: nine new species, a key to identify species, and a novel character to support its monophyly.

    Science.gov (United States)

    Cano, Enio B

    2014-12-02

    Nine new species of Ogyges Kaup (Coleoptera: Passalidae) from the mountainous cloud forests of Mesoamerica are described: O. handali new species and O. menchuae new species from Guatemala; O. cavei new species, O. laurae new species, O. llama new species, O. mutenroshii new species, O. ratcliffei new species, and O. toriyamai new species from Honduras; and O. sandinoi new species from Nicaragua, the first objective record of the genus for this country. A key to the adult Ogyges is included. The work also shows that Ogyges possesses an exclusive autapomorphy: a trituberculate suprainternal tooth of each mandible (one long and wide apical tubercle and two connected, small, almost conical, basal tubercles). This character state is found in all known Ogyges species and is proposed as a synapomorphy that supports the monophyly of the genus.

  16. Robust global identifiability theory using potentials--Application to compartmental models.

    Science.gov (United States)

    Wongvanich, N; Hann, C E; Sirisena, H R

    2015-04-01

    This paper presents a global practical identifiability theory for analyzing and identifying linear and nonlinear compartmental models. The compartmental system is prolonged onto the potential jet space to formulate a set of input-output equations that are integrals in terms of the measured data, which allows for robust identification of parameters without requiring any simulation of the model differential equations. Two classes of linear and non-linear compartmental models are considered. The theory is first applied to analyze the linear nitrous oxide (N2O) uptake model. The fitting accuracy of the identified models from differential jet space and potential jet space identifiability theories is compared with a realistic noise level of 3% which is derived from sensor noise data in the literature. The potential jet space approach gave a match that was well within the coefficient of variation. The differential jet space formulation was unstable and not suitable for parameter identification. The proposed theory is then applied to a nonlinear immunological model for mastitis in cows. In addition, the model formulation is extended to include an iterative method which allows initial conditions to be accurately identified. With up to 10% noise, the potential jet space theory predicts the normalized population concentration infected with pathogens, to within 9% of the true curve. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Understanding of a Key Aspect of Situation Awareness: A Research and Development Agenda to Refine the Model of Spatial Orientation

    Science.gov (United States)

    2017-07-10

    USAARL Report No. 2017-14 Understanding of a Key Aspect of Situation Awareness: A Research and Development Agenda to Refine the Model of Spatial...Understanding of a Key Aspect of Situation Awareness: a Research and Development Agenda to Refine the Model of Spatial Orientation N/A N/A N/A N/A N/A N/A Lawson...supporting the initial model development for military applications by authors Newman, Lawson, and Rupert.  Small Business Innovative Research program

  18. Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

    Science.gov (United States)

    Zhang, Qiong; Huang, Yinping; Zhang, Keke; Huang, Yanjun; Yan, Yan; Wang, Fan; Wu, Jie; Wang, Xiao; Xu, Zhangye; Chen, Yongtao; Cheng, Xue; Li, Yong; Jiao, Jinyu; Ye, Duyun

    2016-11-01

    With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. From conceptual model to remediation: bioavailability, a key to clean up heavy metal contaminated soils.

    Science.gov (United States)

    Petruzzelli, Gianniantonio; Pedron, Francesca; Pezzarossa, Beatrice

    2013-04-01

    that aim to increase the bioavailability of pollutants are used in technologies which remove or destroy the solubilized contaminants. These procedures can increase mass transfer from the absorbed phase by means of sieving in order to decrease the diffusion processes (soil washing), by increasing the temperature (low temperature thermal desorption), or through the addition of chemical additives, such as chelating agents (Phytoextraction Elektrokinetic remediation). Concluding remarks Bioavailability should be a key component of the exposure evaluation in order to develop the conceptual model and to select the technology, in particular when: • only some chemical forms of contaminants are a source of risk for the site; • default assumptions regarding bioavailability are not suitable because of the site's specific characteristics; • the final destination of the site will not be modified at least in the near future.

  20. Examples of testing global identifiability of biological and biomedical models with the DAISY software.

    Science.gov (United States)

    Saccomani, Maria Pia; Audoly, Stefania; Bellu, Giuseppina; D'Angiò, Leontina

    2010-04-01

    DAISY (Differential Algebra for Identifiability of SYstems) is a recently developed computer algebra software tool which can be used to automatically check global identifiability of (linear and) nonlinear dynamic models described by differential equations involving polynomial or rational functions. Global identifiability is a fundamental prerequisite for model identification which is important not only for biological or medical systems but also for many physical and engineering systems derived from first principles. Lack of identifiability implies that the parameter estimation techniques may not fail but any obtained numerical estimates will be meaningless. The software does not require understanding of the underlying mathematical principles and can be used by researchers in applied fields with a minimum of mathematical background. We illustrate the DAISY software by checking the a priori global identifiability of two benchmark nonlinear models taken from the literature. The analysis of these two examples includes comparison with other methods and demonstrates how identifiability analysis is simplified by this tool. Thus we illustrate the identifiability analysis of other two examples, by including discussion of some specific aspects related to the role of observability and knowledge of initial conditions in testing identifiability and to the computational complexity of the software. The main focus of this paper is not on the description of the mathematical background of the algorithm, which has been presented elsewhere, but on illustrating its use and on some of its more interesting features. DAISY is available on the web site http://www.dei.unipd.it/ approximately pia/.

  1. Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAs

    Science.gov (United States)

    2015-02-01

    maintenance of normal stem cells during embryonic development [e.g., Notch , Wnt, and Hedgehog] are also important for the growth of many cancers ...uncovered the biological relevance of this miRNA. We found that miR-181a induced platinum-resistance through the maintenance of cancer stem cells ...primary tumors. Most recently, the first stem - cell population that was able to give rise to ovarian cancers was identified in mice. Cells located

  2. Kinome-wide shRNA Screen Identifies the Receptor Tyrosine Kinase AXL as a Key Regulator for Mesenchymal Glioblastoma Stem-like Cells

    Directory of Open Access Journals (Sweden)

    Peng Cheng

    2015-05-01

    Full Text Available Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs were recently identified: mesenchymal (MES and proneural (PN. To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers.

  3. Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease.

    Science.gov (United States)

    Brownjohn, Philip W; Smith, James; Portelius, Erik; Serneels, Lutgarde; Kvartsberg, Hlin; De Strooper, Bart; Blennow, Kaj; Zetterberg, Henrik; Livesey, Frederick J

    2017-04-11

    Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β (Aβ) peptides are key processes in Alzheimer's disease (AD). We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Natural headland sand bypassing; towards identifying and modelling the mechanisms and processes

    NARCIS (Netherlands)

    Bin Ab Razak, M.S.

    2015-01-01

    Natural headland sand bypassing: Towards identifying and modelling the mechanisms and processes contributes to the understanding of the mechanisms and processes of sand bypassing in artificial and non-artificial coastal environments through a numerical modelling study. Sand bypassing processes in ge

  5. The Baby TALK Model: An Innovative Approach to Identifying High-Risk Children and Families

    Science.gov (United States)

    Villalpando, Aimee Hilado; Leow, Christine; Hornstein, John

    2012-01-01

    This research report examines the Baby TALK model, an innovative early childhood intervention approach used to identify, recruit, and serve young children who are at-risk for developmental delays, mental health needs, and/or school failure, and their families. The report begins with a description of the model. This description is followed by an…

  6. Modeling Success: Using Preenrollment Data to Identify Academically At-Risk Students

    Science.gov (United States)

    Gansemer-Topf, Ann M.; Compton, Jonathan; Wohlgemuth, Darin; Forbes, Greg; Ralston, Ekaterina

    2015-01-01

    Improving student success and degree completion is one of the core principles of strategic enrollment management. To address this principle, institutional data were used to develop a statistical model to identify academically at-risk students. The model employs multiple linear regression techniques to predict students at risk of earning below a…

  7. Study of techniques of identifying the earthquake precursory anomalies in terms of mathematical modeling

    Institute of Scientific and Technical Information of China (English)

    YAN Zun-guo; QIAN Jia-dong; CHEN Jun-hua; LI Sheng-le

    2000-01-01

    This paper deals mainly with the key technique of identifying the anomalous signals without distortion, which might be the precursors associated with earthquakes, from the real time series of observations that would be usually the mixture of the anomalous signals, the normal background variations, some interference and noises. The key technique of 2 un-biased estimation2 is to construct an empirical time series and set up the criterion for identifying the anomalous variation on the bases of time series analysis. To the end of testing the method, a man-made time series including the normal variations and random interference as well as specific anomaly, has been constructed. And the test of picking up the anomaly has been conducted with the intuitive and effective way of identifying the anomalous signal from a complicated time series. Test results confirms that the techniques under discussion are effective and applicable, and the signals extracted from the analysis, could be clear and precise, and is almost similar to the known simulated anomalous signals in the experiments.

  8. Solid images for geostructural mapping and key block modeling of rock discontinuities

    Science.gov (United States)

    Assali, Pierre; Grussenmeyer, Pierre; Villemin, Thierry; Pollet, Nicolas; Viguier, Flavien

    2016-04-01

    Rock mass characterization is obviously a key element in rock fall hazard analysis. Managing risk and determining the most adapted reinforcement method require a proper understanding of the considered rock mass. Description of discontinuity sets is therefore a crucial first step in the reinforcement work design process. The on-field survey is then followed by a structural modeling in order to extrapolate the data collected at the rock surface to the inner part of the massif. Traditional compass survey and manual observations can be undoubtedly surpassed by dense 3D data such as LiDAR or photogrammetric point clouds. However, although the acquisition phase is quite fast and highly automated, managing, handling and exploiting such great amount of collected data is an arduous task and especially for non specialist users. In this study, we propose a combined approached using both 3D point clouds (from LiDAR or image matching) and 2D digital images, gathered into the concept of ''solid image''. This product is the connection between the advantages of classical true colors 2D digital images, accessibility and interpretability, and the particular strengths of dense 3D point clouds, i.e. geometrical completeness and accuracy. The solid image can be considered as the information support for carrying-out a digital survey at the surface of the outcrop without being affected by traditional deficiencies (lack of data and sampling difficulties due to inaccessible areas, safety risk in steep sectors, etc.). Computational tools presented in this paper have been implemented into one standalone software through a graphical user interface helping operators with the completion of a digital geostructural survey and analysis. 3D coordinates extraction, 3D distances and area measurement, planar best-fit for discontinuity orientation, directional roughness profiles, block size estimation, and other tools have been experimented on a calcareous quarry in the French Alps.

  9. Using social network analysis to identify key stakeholders in agricultural biodiversity governance and related land-use decisions at regional and local level

    Directory of Open Access Journals (Sweden)

    Jennifer Hauck

    2016-06-01

    Full Text Available In 2013 the European Commission launched its new green infrastructure strategy to make another attempt to stop and possibly reverse the loss of biodiversity until 2020, by connecting habitats in the wider landscape. This means that conservation would go beyond current practices to include landscapes that are dominated by conventional agriculture, where biodiversity conservation plays a minor role at best. The green infrastructure strategy aims at bottom-up rather than top-down implementation, and suggests including local and regional stakeholders. Therefore, it is important to know which stakeholders influence land-use decisions concerning green infrastructure at the local and regional level. The research presented in this paper served to select stakeholders in preparation for a participatory scenario development process to analyze consequences of different implementation options of the European green infrastructure strategy. We used a mix of qualitative and quantitative social network analysis (SNA methods to combine actors' attributes, especially concerning their perceived influence, with structural and relational measures. Further, our analysis provides information on institutional backgrounds and governance settings for green infrastructure and agricultural policy. The investigation started with key informant interviews at the regional level in administrative units responsible for relevant policies and procedures such as regional planners, representatives of federal ministries, and continued at the local level with farmers and other members of the community. The analysis revealed the importance of information flows and regulations but also of social pressure, considerably influencing biodiversity governance with respect to green infrastructure and biodiversity.

  10. Half-trek criterion for generic identifiability of linear structural equation models

    CERN Document Server

    Foygel, Rina; Drton, Mathias

    2011-01-01

    A linear structural equation model relates random variables of interest and corresponding Gaussian noise terms via a linear equation system. Each such model can be represented by a mixed graph in which directed edges encode the linear equations, and bidirected edges indicate possible correlations among noise terms. We study parameter identifiability in these models, that is, we ask for conditions that ensure that the edge coefficients and correlations appearing in a linear structural equation model can be uniquely recovered from the covariance matrix of the associated normal distribution. We treat the case of generic identifiability, where unique recovery is possible for almost every choice of parameters. We give a new graphical criterion that is sufficient for generic identifiability. It improves criteria from prior work and does not require the directed part of the graph to be acyclic. We also develop a related necessary condition and examine the "gap" between sufficient and necessary conditions through sim...

  11. Model Order and Identifiability of Non-Linear Biological Systems in Stable Oscillation.

    Science.gov (United States)

    Wigren, Torbjörn

    2015-01-01

    The paper presents a theoretical result that clarifies when it is at all possible to determine the nonlinear dynamic equations of a biological system in stable oscillation, from measured data. As it turns out the minimal order needed for this is dependent on the minimal dimension in which the stable orbit of the system does not intersect itself. This is illustrated with a simulated fourth order Hodgkin-Huxley spiking neuron model, which is identified using a non-linear second order differential equation model. The simulated result illustrates that the underlying higher order model of the spiking neuron cannot be uniquely determined given only the periodic measured data. The result of the paper is of general validity when the dynamics of biological systems in stable oscillation is identified, and illustrates the need to carefully address non-linear identifiability aspects when validating models based on periodic data.

  12. A Numerical Procedure for Model Identifiability Analysis Applied to Enzyme Kinetics

    DEFF Research Database (Denmark)

    Daele, Timothy, Van; Van Hoey, Stijn; Gernaey, Krist;

    2015-01-01

    exercise, thereby bypassing the challenging task of model structure determination and identification. Parameter identification problems can thus lead to ill-calibrated models with low predictive power and large model uncertainty. Every calibration exercise should therefore be precededby a proper model...... and Pronzato (1997) and which can be easily set up for any type of model. In this paper the proposed approach is applied to the forward reaction rate of the enzyme kinetics proposed by Shin and Kim(1998). Structural identifiability analysis showed that no local structural model problems were occurring......The proper calibration of models describing enzyme kinetics can be quite challenging. In the literature, different procedures are available to calibrate these enzymatic models in an efficient way. However, in most cases the model structure is already decided on prior to the actual calibration...

  13. Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

    OpenAIRE

    Baker Syed; Poskar C; Junker Björn

    2011-01-01

    Abstract In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. Wh...

  14. Identifiability of Normal and Normal Mixture Models With Nonignorable Missing Data

    OpenAIRE

    Miao, Wang; Ding, Peng; Geng, Zhi

    2015-01-01

    Missing data problems arise in many applied research studies. They may jeopardize statistical inference of the model of interest, if the missing mechanism is nonignorable, that is, the missing mechanism depends on the missing values themselves even conditional on the observed data. With a nonignorable missing mechanism, the model of interest is often not identifiable without imposing further assumptions. We find that even if the missing mechanism has a known parametric form, the model is not ...

  15. A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin.

    Science.gov (United States)

    Reiling, Jan H; Clish, Clary B; Carette, Jan E; Varadarajan, Malini; Brummelkamp, Thijn R; Sabatini, David M

    2011-07-19

    Tunicamycin (TM) inhibits eukaryotic asparagine-linked glycosylation, protein palmitoylation, ganglioside production, proteoglycan synthesis, 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity, and cell wall biosynthesis in bacteria. Treatment of cells with TM elicits endoplasmic reticulum stress and activates the unfolded protein response. Although widely used in laboratory settings for many years, it is unknown how TM enters cells. Here, we identify in an unbiased genetic screen a transporter of the major facilitator superfamily, major facilitator domain containing 2A (MFSD2A), as a critical mediator of TM toxicity. Cells without MFSD2A are TM-resistant, whereas MFSD2A-overexpressing cells are hypersensitive. Hypersensitivity is associated with increased cellular TM uptake concomitant with an enhanced endoplasmic reticulum stress response. Furthermore, MFSD2A mutant analysis reveals an important function of the C terminus for correct intracellular localization and protein stability, and it identifies transmembrane helical amino acid residues essential for mediating TM sensitivity. Overall, our data uncover a critical role for MFSD2A by acting as a putative TM transporter at the plasma membrane.

  16. Detailed profiling of anti-desmoglein autoantibodies identifies anti-Dsg1 reactivity as a key driver of disease activity and clinical expression in pemphigus vulgaris.

    Science.gov (United States)

    Naseer, S Y; Seiffert-Sinha, K; Sinha, A A

    2015-06-01

    With their near-universal presence in patients and ease of clinical measurement, anti-desmoglein (Dsg) antibodies serve as primary candidates for creating prognostic tools in Pemphigus vulgaris (PV). Although the desmoglein compensation hypothesis postulates a clear relationship between anti-Dsg autoantibodies and clinical phenotype in PV, recent studies have questioned the fidelity of this hypothesis as a predictor of lesion morphology. Moreover, few studies address the association of anti-Dsg antibodies to other clinical parameters such as disease phase and age at onset. Using the largest patient repository to date in PV, we present a detailed analysis of anti-desmoglein antibody profiles across a comprehensive range of dynamic (disease phase, therapy, lesion morphology) and temporal (disease duration, age at sampling, age at onset) clinical parameters. Our data highlight the non-traditional but key role of anti-Dsg1 levels in tracking disease activity. We show that declining anti-Dsg1 levels may predict progression from active phase to early remission and long-term maintenance of remission, regardless of lesion morphology. In contrast, many remittent patients have elevated levels of anti-Dsg3 without lesional activity. Furthermore, we describe a unique subset of remittent patients that develop chronic transient lesions (lasting <1 week) in the setting of elevated anti-Dsg3 levels but do not meet the consensus criteria for active phase. Re-classification of patients with transient lesions as "active" may shed new light on pathophysiological processes underlying cycles of blister formation and rapid spontaneous healing in PV. Additionally, we provide evidence for the potential attenuation of the immune response with prolonged disease duration. Our data fit into the broader effort of immunoprofiling to promote data-informed decision-making regarding diagnosis, prognosis and treatment of complex diseases.

  17. Exploiting RNA-sequencing data from the porcine testes to identify the key genes involved in spermatogenesis in Large White pigs.

    Science.gov (United States)

    Song, Huibin; Zhu, Lihua; Li, Yan; Ma, Changping; Guan, Kaifeng; Xia, Xuanyan; Li, Fenge

    2015-12-01

    Mammalian testis development and spermatogenesis play critical roles in male fertility. However, little genomic information is available for porcine sexually mature and immature testis. Presently, we detected approximately 76% of previously annotated genes that were expressed in the porcine testes by RNA sequencing. Taking an FDR of 0.001 and a |log2Ratio| of 1 as cutoffs, 10,095 genes were significantly differentially expressed between two stages, including 242 spermatogenesis-associated genes. These genes were significantly enriched to GO BP terms concerning spermatogenesis, male gamete generation, developmental process and sexual reproduction; to the KEEG pathways, including focal adhesion, ECM-receptor interaction, and phagosome. 186 extended transcripts, 1273 alternative splicing events and 2846 SNPs were detected in spermatogenesis-associated DEGs. Two PIWIL4 SNPs were successfully validated and suggested to be the potential molecular markers for semen quality. This study will help identify the specific genes and isoforms that are active in porcine spermatogenesis and sexual maturity.

  18. Vertebrae classification models - Validating classification models that use morphometrics to identify ancient salmonid (Oncorhynchus spp.) vertebrae to species

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Using morphometric characteristics of modern salmonid (Oncorhynchus spp.) vertebrae, we have developed classification models to identify salmonid vertebrae to the...

  19. Structural identifiability of systems biology models: a critical comparison of methods.

    Directory of Open Access Journals (Sweden)

    Oana-Teodora Chis

    Full Text Available Analysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.

  20. Calibrating and Validating a Simulation Model to Identify Drivers of Urban Land Cover Change in the Baltimore, MD Metropolitan Region

    Directory of Open Access Journals (Sweden)

    Claire Jantz

    2014-09-01

    Full Text Available We build upon much of the accumulated knowledge of the widely used SLEUTH urban land change model and offer advances. First, we use SLEUTH’s exclusion/attraction layer to identify and test different urban land cover change drivers; second, we leverage SLEUTH’s self-modification capability to incorporate a demographic model; and third, we develop a validation procedure to quantify the influence of land cover change drivers and assess uncertainty. We found that, contrary to our a priori expectations, new development is not attracted to areas serviced by existing or planned water and sewer infrastructure. However, information about where population and employment growth is likely to occur did improve model performance. These findings point to the dominant role of centrifugal forces in post-industrial cities like Baltimore, MD. We successfully developed a demographic model that allowed us to constrain the SLEUTH model forecasts and address uncertainty related to the dynamic relationship between changes in population and employment and urban land use. Finally, we emphasize the importance of model validation. In this work the validation procedure played a key role in rigorously assessing the impacts of different exclusion/attraction layers and in assessing uncertainty related to population and employment forecasts.

  1. Comprehensive Profiling of Ethylene Response Factor Expression Identifies Ripening-Associated ERF Genes and Their Link to Key Regulators of Fruit Ripening in Tomato.

    Science.gov (United States)

    Liu, Mingchun; Gomes, Bruna Lima; Mila, Isabelle; Purgatto, Eduardo; Peres, Lázaro E P; Frasse, Pierre; Maza, Elie; Zouine, Mohamed; Roustan, Jean-Paul; Bouzayen, Mondher; Pirrello, Julien

    2016-03-01

    Our knowledge of the factors mediating ethylene-dependent ripening of climacteric fruit remains limited. The transcription of ethylene-regulated genes is mediated by ethylene response factors (ERFs), but mutants providing information on the specific role of the ERFs in fruit ripening are still lacking, likely due to functional redundancy among this large multigene family of transcription factors. We present here a comprehensive expression profiling of tomato (Solanum lycopersicum) ERFs in wild-type and tomato ripening-impaired tomato mutants (Never-ripe [Nr], ripening-inhibitor [rin], and non-ripening [nor]), indicating that out of the 77 ERFs present in the tomato genome, 27 show enhanced expression at the onset of ripening while 28 display a ripening-associated decrease in expression, suggesting that different ERFs may have contrasting roles in fruit ripening. Among the 19 ERFs exhibiting the most consistent up-regulation during ripening, the expression of 11 ERFs is strongly down-regulated in rin, nor, and Nr tomato ripening mutants, while only three are consistently up-regulated. Members of subclass E, SlERF.E1, SlERF.E2, and SlERF.E4, show dramatic down-regulation in the ripening mutants, suggesting that their expression might be instrumental in fruit ripening. This study illustrates the high complexity of the regulatory network connecting RIN and ERFs and identifies subclass E members as the most active ERFs in ethylene- and RIN/NOR-dependent ripening.

  2. Paving the Way to Successful Implementation: Identifying Key Barriers to Use of Technology-Based Therapeutic Tools for Behavioral Health Care.

    Science.gov (United States)

    Ramsey, Alex; Lord, Sarah; Torrey, John; Marsch, Lisa; Lardiere, Michael

    2016-01-01

    This study aimed to identify barriers to use of technology for behavioral health care from the perspective of care decision makers at community behavioral health organizations. As part of a larger survey of technology readiness, 260 care decision makers completed an open-ended question about perceived barriers to use of technology. Using the Consolidated Framework for Implementation Research (CFIR), qualitative analyses yielded barrier themes related to characteristics of technology (e.g., cost and privacy), potential end users (e.g., technology literacy and attitudes about technology), organization structure and climate (e.g., budget and infrastructure), and factors external to organizations (e.g., broadband accessibility and reimbursement policies). Number of reported barriers was higher among respondents representing agencies with lower annual budgets and smaller client bases relative to higher budget, larger clientele organizations. Individual barriers were differentially associated with budget, size of client base, and geographic location. Results are discussed in light of implementation science frameworks and proactive strategies to address perceived obstacles to adoption and use of technology-based behavioral health tools.

  3. A biophysical model for identifying splicing regulatory elements and their interactions.

    Directory of Open Access Journals (Sweden)

    Ji Wen

    Full Text Available Alternative splicing (AS of precursor mRNA (pre-mRNA is a crucial step in the expression of most eukaryotic genes. Splicing factors (SFs play an important role in AS regulation by binding to the cis-regulatory elements on the pre-mRNA. Although many splicing factors (SFs and their binding sites have been identified, their combinatorial regulatory effects remain to be elucidated. In this paper, we derive a biophysical model for AS regulation that integrates combinatorial signals of cis-acting splicing regulatory elements (SREs and their interactions. We also develop a systematic framework for model inference. Applying the biophysical model to a human RNA-Seq data set, we demonstrate that our model can explain 49.1%-66.5% variance of the data, which is comparable to the best result achieved by biophysical models for transcription. In total, we identified 119 SRE pairs between different regions of cassette exons that may regulate exon or intron definition in splicing, and 77 SRE pairs from the same region that may arise from a long motif or two different SREs bound by different SFs. Particularly, putative binding sites of polypyrimidine tract-binding protein (PTB, heterogeneous nuclear ribonucleoprotein (hnRNP F/H and E/K are identified as interacting SRE pairs, and have been shown to be consistent with the interaction models proposed in previous experimental results. These results show that our biophysical model and inference method provide a means of quantitative modeling of splicing regulation and is a useful tool for identifying SREs and their interactions. The software package for model inference is available under an open source license.

  4. Identifying best-fitting inputs in health-economic model calibration: a Pareto frontier approach.

    Science.gov (United States)

    Enns, Eva A; Cipriano, Lauren E; Simons, Cyrena T; Kong, Chung Yin

    2015-02-01

    To identify best-fitting input sets using model calibration, individual calibration target fits are often combined into a single goodness-of-fit (GOF) measure using a set of weights. Decisions in the calibration process, such as which weights to use, influence which sets of model inputs are identified as best-fitting, potentially leading to different health economic conclusions. We present an alternative approach to identifying best-fitting input sets based on the concept of Pareto-optimality. A set of model inputs is on the Pareto frontier if no other input set simultaneously fits all calibration targets as well or better. We demonstrate the Pareto frontier approach in the calibration of 2 models: a simple, illustrative Markov model and a previously published cost-effectiveness model of transcatheter aortic valve replacement (TAVR). For each model, we compare the input sets on the Pareto frontier to an equal number of best-fitting input sets according to 2 possible weighted-sum GOF scoring systems, and we compare the health economic conclusions arising from these different definitions of best-fitting. For the simple model, outcomes evaluated over the best-fitting input sets according to the 2 weighted-sum GOF schemes were virtually nonoverlapping on the cost-effectiveness plane and resulted in very different incremental cost-effectiveness ratios ($79,300 [95% CI 72,500-87,600] v. $139,700 [95% CI 79,900-182,800] per quality-adjusted life-year [QALY] gained). Input sets on the Pareto frontier spanned both regions ($79,000 [95% CI 64,900-156,200] per QALY gained). The TAVR model yielded similar results. Choices in generating a summary GOF score may result in different health economic conclusions. The Pareto frontier approach eliminates the need to make these choices by using an intuitive and transparent notion of optimality as the basis for identifying best-fitting input sets. © The Author(s) 2014.

  5. Identifying the molecular basis of host-parasite coevolution: merging models and mechanisms.

    Science.gov (United States)

    Dybdahl, Mark F; Jenkins, Christina E; Nuismer, Scott L

    2014-07-01

    Mathematical models of the coevolutionary process have uncovered consequences of host-parasite interactions that go well beyond the traditional realm of the Red Queen, potentially explaining several important evolutionary transitions. However, these models also demonstrate that the specific consequences of coevolution are sensitive to the structure of the infection matrix, which is embedded in models to describe the likelihood of infection in encounters between specific host and parasite genotypes. Traditional cross-infection approaches to estimating infection matrices might be unreliable because evolutionary dynamics and experimental sampling lead to missing genotypes. Consequently, our goal is to identify the likely structure of infection matrices by synthesizing molecular mechanisms of host immune defense and parasite counterdefense with coevolutionary models. This synthesis reveals that the molecular mechanisms of immune reactions, although complex and diverse, conform to two basic models commonly used within coevolutionary theory: matching infection and targeted recognition. Our synthesis also overturns conventional wisdom, revealing that the general models are not taxonomically restricted but are applicable to plants, invertebrates, and vertebrates. Finally, our synthesis identifies several important areas for future research that should improve the explanatory power of coevolutionary models. The most important among these include empirical studies to identify the molecular hotspots of genotypic specificity and theoretical studies examining the consequences of matrices that more accurately represent multistep infection processes and quantitative defenses.

  6. Validation of a Predictive Model to Identify Patients at High Risk for Hospital Readmission.

    Science.gov (United States)

    Spiva, LeeAnna; Hand, Marti; VanBrackle, Lewis; McVay, Frank

    2016-01-01

    Hospital readmission is an adverse patient outcome that is serious, common, and costly. For hospitals, identifying patients at risk for hospital readmission is a priority to reduce costs and improve care. The purposes were to validate a predictive algorithm to identify patients at a high risk for preventable hospital readmission within 30 days after discharge and determine if additional risk factors enhance readmission predictability. A retrospective study was conducted on a randomized sample of 598 patients discharged from a Southeast community hospital. Data were collected from the organization's database and manually abstracted from the electronic medical record using a structured tool. Two separate logistic regression models were fit for the probability of readmission within 30 days after discharge. The first model used the LACE index as the predictor variable, and the second model used the LACE index with additional risk factors. The two models were compared to determine if additional risk factors increased the model's predictive ability. The results indicate both models have reasonable prognostic capability. The LACE index with additional risk factors did little to improve prognostication, while adding to the model's complexity. Findings support the use of the LACE index as a practical tool to identify patients at risk for readmission.

  7. Improving the precision of lake ecosystem metabolism estimates by identifying predictors of model uncertainty

    Science.gov (United States)

    Rose, Kevin C.; Winslow, Luke A.; Read, Jordan S.; Read, Emily K.; Solomon, Christopher T.; Adrian, Rita; Hanson, Paul C.

    2014-01-01

    Diel changes in dissolved oxygen are often used to estimate gross primary production (GPP) and ecosystem respiration (ER) in aquatic ecosystems. Despite the widespread use of this approach to understand ecosystem metabolism, we are only beginning to understand the degree and underlying causes of uncertainty for metabolism model parameter estimates. Here, we present a novel approach to improve the precision and accuracy of ecosystem metabolism estimates by identifying physical metrics that indicate when metabolism estimates are highly uncertain. Using datasets from seventeen instrumented GLEON (Global Lake Ecological Observatory Network) lakes, we discovered that many physical characteristics correlated with uncertainty, including PAR (photosynthetically active radiation, 400-700 nm), daily variance in Schmidt stability, and wind speed. Low PAR was a consistent predictor of high variance in GPP model parameters, but also corresponded with low ER model parameter variance. We identified a threshold (30% of clear sky PAR) below which GPP parameter variance increased rapidly and was significantly greater in nearly all lakes compared with variance on days with PAR levels above this threshold. The relationship between daily variance in Schmidt stability and GPP model parameter variance depended on trophic status, whereas daily variance in Schmidt stability was consistently positively related to ER model parameter variance. Wind speeds in the range of ~0.8-3 m s–1 were consistent predictors of high variance for both GPP and ER model parameters, with greater uncertainty in eutrophic lakes. Our findings can be used to reduce ecosystem metabolism model parameter uncertainty and identify potential sources of that uncertainty.

  8. Pupal-productivity surveys to identify the key container habitats of Aedes aegypti (L.) in Barranquilla, the principal seaport of Colombia.

    Science.gov (United States)

    Romero-Vivas, C M E; Arango-Padilla, P; Falconar, A K I

    2006-04-01

    Surveys were conducted in three neighbourhoods of Barranquilla, the main seaport of Colombia, to identify, using counts of pupae in water containers during the wet and dry seasons, the most productive Aedes aegypti breeding sites. Overall, 3,433 premises were investigated in the wet season and 3,563 in the dry, representing, respectively, 82.3% and 84.6% of the total numbers of premises in the study areas. Despite a reasonably reliable supply of piped water, there were still some large storage containers for domestic water (cement ground tanks and plastic, metal and cement drums) in the area. Although such containers represented only 1.8%-16.3% of the total number of containers observed, they contributed 72.0%-78.2% and 65.0%-95.8% of the total Ae. aegypti pupal population in the three study neighbourhoods during the wet and dry seasons, respectively. In contrast, bottles represented 23.0%-88.9% of the total number of containers but produced no more than 0.1% of the total Ae aegypti pupal populations in these neighbourhoods. Other containers (tyres, vases, 'other discarded' and 'other used') generally produced only low numbers of pupae. In some settings, however, containers in the 'other discarded' category could contribute up to 19% of the total pupal population, and in one survey of one neighbourhood a single container in this category held 9.1% of all the pupae collected. These results, from a city where dengue fever is endemic, will help to focus local campaigns for Ae. aegypti source-reduction on the most productive categories of container.

  9. The green shoots of a novel training programme: progress and identified key actions to providing services to MSM at Kenyan health facilities

    Directory of Open Access Journals (Sweden)

    Elise M van der Elst

    2015-10-01

    Full Text Available Introduction: Although men who have sex with men (MSM in sub-Saharan Africa are at high risk for HIV acquisition, access to and quality of health and HIV services within this population are negatively affected by stigma and capacity within the health sector. A recently developed online MSM training programme (www.marps-africa.org was shown to contribute to reductions in MSM prejudice among healthcare providers (HCPs in coastal Kenya. In this study, we used qualitative methods to explore the provision of MSM healthcare services two years post-training in coastal Kenya. Methods: From February to July 2014, we held 10 focus group discussions (FGD with 63 participants, including HCP from 25 facilities, county AIDS coordinators and MSM from local support groups. Participants discussed availability, acceptability and accessibility of HIV healthcare for MSM. HCP also discussed changes in their health service practices after completing the training. FGD were recorded, transcribed verbatim and analyzed using Ritchie and Spencer's “framework approach” for qualitative data. Results: HCPs described continued improvements in their ability to provide service in a non-stigmatizing way to MSM patients since completing the training programme and expressed comfort engaging MSM patients in care. Four additional recommendations for improving MSM healthcare services were identified: 1 expanding the reach of MSM sensitivity training across the medical education continuum; 2 establishing guidelines to manage sexually transmitted anal infections; 3 promoting legal and policy reforms to support integration of MSM-appropriate services into healthcare; and 4 including MSM information in national reporting tools for HIV services. Conclusions: Positive impacts of this sensitivity and skills training programme were reflected in HCP attitudes two years post-intervention. Scaling-up of efforts will rely on continued policies to include MSM in healthcare programmes to

  10. Self-Organized Public-Key Management for Mobile Ad Hoc Networks Based on a Bidirectional Trust Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In traditional networks ,the authentication is performed by certificate authoritys(CA),which can't be built in distributed mobile Ad Hoc Networks however. In this paper, we propose a fully self-organized public key management based on bidirectional trust model without any centralized authority that allows users to generate their public-private key pairs, to issue certificates, and the trust relation spreads rationally according to the truly human relations. In contrast with the traditional self-organized public-key management, the average certificates paths get more short,the authentication passing rate gets more high and the most important is that the bidirectional trust based model satisfys the trust requirement of hosts better.

  11. A review on statistical models for identifying climate contributions to crop yields

    Institute of Scientific and Technical Information of China (English)

    SHI Wenjiao; TAO Fulu; ZHANG Zhao

    2013-01-01

    Statistical models using historical data on crop yields and weather to calibrate relatively simple regression equations have been widely and extensively applied in previous studies,and have provided a common alternative to process-based models,which require extensive input data on cultivar,management,and soil conditions.However,very few studies had been conducted to review systematically the previous statistical models for indentifying climate contributions to crop yields.This paper introduces three main statistical methods,i.e.,time-series model,cross-section model and panel model,which have been used to identify such issues in the field of agrometeorology.Generally,research spatial scale could be categorized into two types using statistical models,including site scale and regional scale (e.g.global scale,national scale,provincial scale and county scale).Four issues exist in identifying response sensitivity of crop yields to climate change by statistical models.The issues include the extent of spatial and temporal scale,non-climatic trend removal,colinearity existing in climate variables and non-consideration of adaptations.Respective resolutions for the above four issues have been put forward in the section of perspective on the future of statistical models finally.

  12. A model to identify high crash road segments with the dynamic segmentation method.

    Science.gov (United States)

    Boroujerdian, Amin Mirza; Saffarzadeh, Mahmoud; Yousefi, Hassan; Ghassemian, Hassan

    2014-12-01

    Currently, high social and economic costs in addition to physical and mental consequences put road safety among most important issues. This paper aims at presenting a novel approach, capable of identifying the location as well as the length of high crash road segments. It focuses on the location of accidents occurred along the road and their effective regions. In other words, due to applicability and budget limitations in improving safety of road segments, it is not possible to recognize all high crash road segments. Therefore, it is of utmost importance to identify high crash road segments and their real length to be able to prioritize the safety improvement in roads. In this paper, after evaluating deficiencies of the current road segmentation models, different kinds of errors caused by these methods are addressed. One of the main deficiencies of these models is that they can not identify the length of high crash road segments. In this paper, identifying the length of high crash road segments (corresponding to the arrangement of accidents along the road) is achieved by converting accident data to the road response signal of through traffic with a dynamic model based on the wavelet theory. The significant advantage of the presented method is multi-scale segmentation. In other words, this model identifies high crash road segments with different lengths and also it can recognize small segments within long segments. Applying the presented model into a real case for identifying 10-20 percent of high crash road segment showed an improvement of 25-38 percent in relative to the existing methods.

  13. Modeling halotropism : a key role for root tip architecture and reflux loop remodeling in redistributing auxin

    NARCIS (Netherlands)

    van den Berg, Thea; Korver, Ruud A; Testerink, Christa; ten Tusscher, Kirsten

    2016-01-01

    A key characteristic of plant development is its plasticity in response to various and dynamically changing environmental conditions. Tropisms contribute to this flexibility by allowing plant organs to grow from or towards environmental cues. Halotropism is a recently described tropism in which plan

  14. Modeling Key Drivers of E-Learning Satisfaction among Student Teachers

    Science.gov (United States)

    Teo, Timothy; Wong, Su Luan

    2013-01-01

    This study explored the key drivers of student teachers' e-learning satisfaction. Three hundred and eighty-seven participants completed a survey questionnaire measuring their self-reported responses to six constructs (tutor quality, perceived usefulness, perceived ease of use, course delivery, facilitating conditions, and course satisfaction).…

  15. Identifying key climate and environmental factors affecting rates of post-fire big sagebrush (Artemisia tridentata) recovery in the northern Columbia Basin, USA

    Science.gov (United States)

    Shinneman, Douglas; McIlroy, Susan

    2016-01-01

    Sagebrush steppe of North America is considered highly imperilled, in part owing to increased fire frequency. Sagebrush ecosystems support numerous species, and it is important to understand those factors that affect rates of post-fire sagebrush recovery. We explored recovery of Wyoming big sagebrush (Artemisia tridentata ssp.wyomingensis) and basin big sagebrush (A. tridentata ssp. tridentata) communities following fire in the northern Columbia Basin (Washington, USA). We sampled plots across 16 fires that burned in big sagebrush communities from 5 to 28 years ago, and also sampled nearby unburned locations. Mixed-effects models demonstrated that density of large–mature big sagebrush plants and percentage cover of big sagebrush were higher with time since fire and in plots with more precipitation during the winter immediately following fire, but were lower when precipitation the next winter was higher than average, especially on soils with higher available water supply, and with greater post-fire mortality of mature big sagebrush plants. Bunchgrass cover 5 to 28 years after fire was predicted to be lower with higher cover of both shrubs and non-native herbaceous species, and only slightly higher with time. Post-fire recovery of big sagebrush in the northern Columbia Basin is a slow process that may require several decades on average, but faster recovery rates may occur under specific site and climate conditions.

  16. Identifying and Quantifying Emergent Behavior Through System of Systems Modeling and Simulation

    Science.gov (United States)

    2015-09-01

    EMERGENT BEHAVIOR THROUGH SYSTEM OF SYSTEMS MODELING AND SIMULATION by Mary Ann Cummings September 2015 Dissertation Supervisor: Man-Tak Shing...COVERED Ph.D. Dissertation 4. TITLE AND SUBTITLE IDENTIFYING AND QUANTIFYING EMERGENT BEHAVIOR THROUGH SYSTEM OF SYSTEMS MODELING AND SIMULATION 5...functionality and interfaces in these SoSs. An inherent deficiency of existing M&S approaches, however, lies in the emergent behavior that occurs as a result of

  17. Identifying the default mode network structure using dynamic causal modeling on resting-state functional magnetic resonance imaging.

    Science.gov (United States)

    Di, Xin; Biswal, Bharat B

    2014-02-01

    The default mode network is part of the brain structure that shows higher neural activity and energy consumption when one is at rest. The key regions in the default mode network are highly interconnected as conveyed by both the white matter fiber tracing and the synchrony of resting-state functional magnetic resonance imaging signals. However, the causal information flow within the default mode network is still poorly understood. The current study used the dynamic causal modeling on a resting-state fMRI data set to identify the network structure underlying the default mode network. The endogenous brain fluctuations were explicitly modeled by Fourier series at the low frequency band of 0.01-0.08Hz, and those Fourier series were set as driving inputs of the DCM models. Model comparison procedures favored a model wherein the MPFC sends information to the PCC and the bilateral inferior parietal lobule sends information to both the PCC and MPFC. Further analyses provide evidence that the endogenous connectivity might be higher in the right hemisphere than in the left hemisphere. These data provided insight into the functions of each node in the DMN, and also validate the usage of DCM on resting-state fMRI data.

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

    Science.gov (United States)

    Rothenberger, Michael J.

    This dissertation examines the fundamental challenge of optimally shaping input trajectories to maximize parameter identifiability of control-oriented lithium-ion battery models. Identifiability is a property from information theory that determines the solvability of parameter estimation for mathematical models using input-output measurements. This dissertation creates a framework that exploits the Fisher information metric to quantify the level of battery parameter identifiability, optimizes this metric through input shaping, and facilitates faster and more accurate estimation. The popularity of lithium-ion batteries is growing significantly in the energy storage domain, especially for stationary and transportation applications. While these cells have excellent power and energy densities, they are plagued with safety and lifespan concerns. These concerns are often resolved in the industry through conservative current and voltage operating limits, which reduce the overall performance and still lack robustness in detecting catastrophic failure modes. New advances in automotive battery management systems mitigate these challenges through the incorporation of model-based control to increase performance, safety, and lifespan. To achieve these goals, model-based control requires accurate parameterization of the battery model. While many groups in the literature study a variety of methods to perform battery parameter estimation, a fundamental issue of poor parameter identifiability remains apparent for lithium-ion battery models. This fundamental challenge of battery identifiability is studied extensively in the literature, and some groups are even approaching the problem of improving the ability to estimate the model parameters. The first approach is to add additional sensors to the battery to gain more information that is used for estimation. The other main approach is to shape the input trajectories to increase the amount of information that can be gained from input

  19. Comparison of two model approaches in the Zambezi river basin with regard to model reliability and identifiability

    Directory of Open Access Journals (Sweden)

    H. C. Winsemius

    2006-01-01

    Full Text Available Variations of water stocks in the upper Zambezi river basin have been determined by 2 different hydrological modelling approaches. The purpose was to provide preliminary terrestrial storage estimates in the upper Zambezi, which will be compared with estimates derived from the Gravity Recovery And Climate Experiment (GRACE in a future study. The first modelling approach is GIS-based, distributed and conceptual (STREAM. The second approach uses Lumped Elementary Watersheds identified and modelled conceptually (LEW. The STREAM model structure has been assessed using GLUE (Generalized Likelihood Uncertainty Estimation a posteriori to determine parameter identifiability. The LEW approach could, in addition, be tested for model structure, because computational efforts of LEW are low. Both models are threshold models, where the non-linear behaviour of the Zambezi river basin is explained by a combination of thresholds and linear reservoirs. The models were forced by time series of gauged and interpolated rainfall. Where available, runoff station data was used to calibrate the models. Ungauged watersheds were generally given the same parameter sets as their neighbouring calibrated watersheds. It appeared that the LEW model structure could be improved by applying GLUE iteratively. Eventually, it led to better identifiability of parameters and consequently a better model structure than the STREAM model. Hence, the final model structure obtained better represents the true hydrology. After calibration, both models show a comparable efficiency in representing discharge. However the LEW model shows a far greater storage amplitude than the STREAM model. This emphasizes the storage uncertainty related to hydrological modelling in data-scarce environments such as the Zambezi river basin. It underlines the need and potential for independent observations of terrestrial storage to enhance our understanding and modelling capacity of the hydrological processes. GRACE

  20. Using Predictive Modelling to Identify Students at Risk of Poor University Outcomes

    Science.gov (United States)

    Jia, Pengfei; Maloney, Tim

    2015-01-01

    Predictive modelling is used to identify students at risk of failing their first-year courses and not returning to university in the second year. Our aim is twofold. Firstly, we want to understand the factors that lead to poor first-year experiences at university. Secondly, we want to develop simple, low-cost tools that would allow universities to…

  1. Inference in partially identified models with many moment inequalities using Lasso

    DEFF Research Database (Denmark)

    Bugni, Federico A.; Caner, Mehmet; Kock, Anders Bredahl;

    This paper considers the problem of inference in a partially identified moment (in)equality model with possibly many moment inequalities. Our contribution is to propose a novel two-step new inference method based on the combination of two ideas. On the one hand, our test statistic and critical va...

  2. Animal model for identifying therapetucually useful compounds for the treatment of sporadic amyotrophic lateral sclerosis

    OpenAIRE

    Gil Ayuso-Gontán, Carmen; Martínez, Ana

    2012-01-01

    [EN] The invention relates to a method for identifying compounds that are potentially useful for the treatment of sporadic amyotrophic lateral sclerosis (ALS), comprising the use of an animal model of rats, developed by means of the administration of β-Ν-methylamino-L-alanine (L-BMAA)

  3. Animal model for identifying therapetucually useful compounds for the treatment of sporadic amyotrophic lateral sclerosis

    OpenAIRE

    Gil, Carmen; Martínez, Ana

    2012-01-01

    [EN] The invention relates to a method for identifying compounds that are potentially useful for the treatment of sporadic amyotrophic lateral sclerosis (ALS), comprising the use of an animal model of rats, developed by means of the administration of β-Ν-methylamino-L-alanine (L-BMAA)

  4. Identifying differentially methylated genes using mixed effect and generalized least square models

    Directory of Open Access Journals (Sweden)

    Yan Pearlly S

    2009-12-01

    Full Text Available Abstract Background DNA methylation plays an important role in the process of tumorigenesis. Identifying differentially methylated genes or CpG islands (CGIs associated with genes between two tumor subtypes is thus an important biological question. The methylation status of all CGIs in the whole genome can be assayed with differential methylation hybridization (DMH microarrays. However, patient samples or cell lines are heterogeneous, so their methylation pattern may be very different. In addition, neighboring probes at each CGI are correlated. How these factors affect the analysis of DMH data is unknown. Results We propose a new method for identifying differentially methylated (DM genes by identifying the associated DM CGI(s. At each CGI, we implement four different mixed effect and generalized least square models to identify DM genes between two groups. We compare four models with a simple least square regression model to study the impact of incorporating random effects and correlations. Conclusions We demonstrate that the inclusion (or exclusion of random effects and the choice of correlation structures can significantly affect the results of the data analysis. We also assess the false discovery rate of different models using CGIs associated with housekeeping genes.

  5. Use of the shared frailty model to identify the determinants of child ...

    African Journals Online (AJOL)

    user

    improving child survival during 5 years preceding the 2005 RDHS, all the achievements ... identify and rank order the most important factors that contributed to child survival ... observed differential performance in child survival are still not well known .... tool is the hazard function such that the Cox PH model for the individual.

  6. Research on identifying the dynamic error model of strapdown gyro on 3-axis turntable

    Institute of Scientific and Technical Information of China (English)

    WANG Hai; REN Shun-qing; WANG Chang-hong

    2005-01-01

    The dynamic errors of gyros are the important error sources of a strapdown inertial navigation system.In order to identify the dynamic error model coefficients accurately, the static erTor model coefficients which lay a foundation for compensating while identifying the dynamic error model are identified in the gravity acceleration fields by using angular position function of the three-axis turntable. The angular acceleration and angular velocity are excited on the input, output and spin axis of the gyros when the outer axis and the middle axis of a threeaxis turntable are in the uniform angular velocity state simultaneously, while the inner axis of the turntable is in different static angular positions. 8 groups of data are sampled when the inner axis is in 8 different angular positions. These data are the function of the middle axis positions and the inner axis positions. For these data, harmonic analysis method is applied two times versus the middle axis positions and inner axis positions respectively so that the dynamic error model coefficients are finally identified through the least square method. In the meantime the optimal angular velocity of the outer axis and the middle axis are selected by computing the determination value of the information matrix.

  7. Structural identifiability analyses of candidate models for in vitro Pitavastatin hepatic uptake.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Michael J; Yates, James W T; Evans, Neil D

    2014-05-01

    In this paper a review of the application of four different techniques (a version of the similarity transformation approach for autonomous uncontrolled systems, a non-differential input/output observable normal form approach, the characteristic set differential algebra and a recent algebraic input/output relationship approach) to determine the structural identifiability of certain in vitro nonlinear pharmacokinetic models is provided. The Organic Anion Transporting Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear compartmental models have been derived to characterise the uptake process of Pitavastatin. As a prerequisite to parameter estimation, structural identifiability analyses are performed to establish that all unknown parameters can be identified from the experimental observations available.

  8. IDENTIFYING OPERATIONAL REQUIREMENTS TO SELECT SUITABLE DECISION MODELS FOR A PUBLIC SECTOR EPROCUREMENT DECISION SUPPORT SYSTEM

    Directory of Open Access Journals (Sweden)

    Mohamed Adil

    2014-10-01

    Full Text Available Public sector procurement should be a transparent and fair process. Strict legal requirements are enforced on public sector procurement to make it a standardised process. To make fair decisions on selecting suppliers, a practical method which adheres to legal requirements is important. The research that is the base for this paper aimed at identifying a suitable Multi-Criteria Decision Analysis (MCDA method for the specific legal and functional needs of the Maldivian Public Sector. To identify such operational requirements, a set of focus group interviews were conducted in the Maldives with public officials responsible for procurement decision making. Based on the operational requirements identified through focus groups, criteria-based evaluation is done on published MCDA methods to identify the suitable methods for e-procurement decision making. This paper describes the identification of the operational requirements and the results of the evaluation to select suitable decision models for the Maldivian context.

  9. Antibiotic Resistances in Livestock: A Comparative Approach to Identify an Appropriate Regression Model for Count Data

    Directory of Open Access Journals (Sweden)

    Anke Hüls

    2017-05-01

    Full Text Available Antimicrobial resistance in livestock is a matter of general concern. To develop hygiene measures and methods for resistance prevention and control, epidemiological studies on a population level are needed to detect factors associated with antimicrobial resistance in livestock holdings. In general, regression models are used to describe these relationships between environmental factors and resistance outcome. Besides the study design, the correlation structures of the different outcomes of antibiotic resistance and structural zero measurements on the resistance outcome as well as on the exposure side are challenges for the epidemiological model building process. The use of appropriate regression models that acknowledge these complexities is essential to assure valid epidemiological interpretations. The aims of this paper are (i to explain the model building process comparing several competing models for count data (negative binomial model, quasi-Poisson model, zero-inflated model, and hurdle model and (ii to compare these models using data from a cross-sectional study on antibiotic resistance in animal husbandry. These goals are essential to evaluate which model is most suitable to identify potential prevention measures. The dataset used as an example in our analyses was generated initially to study the prevalence and associated factors for the appearance of cefotaxime-resistant Escherichia coli in 48 German fattening pig farms. For each farm, the outcome was the count of samples with resistant bacteria. There was almost no overdispersion and only moderate evidence of excess zeros in the data. Our analyses show that it is essential to evaluate regression models in studies analyzing the relationship between environmental factors and antibiotic resistances in livestock. After model comparison based on evaluation of model predictions, Akaike information criterion, and Pearson residuals, here the hurdle model was judged to be the most appropriate

  10. Identifying 'unhealthy' food advertising on television: a case study applying the UK Nutrient Profile model.

    Science.gov (United States)

    Jenkin, Gabrielle; Wilson, Nick; Hermanson, Nicole

    2009-05-01

    To evaluate the feasibility of the UK Nutrient Profile (NP) model for identifying 'unhealthy' food advertisements using a case study of New Zealand television advertisements. Four weeks of weekday television from 15.30 hours to 18.30 hours was videotaped from a state-owned (free-to-air) television channel popular with children. Food advertisements were identified and their nutritional information collected in accordance with the requirements of the NP model. Nutrient information was obtained from a variety of sources including food labels, company websites and a national nutritional database. From the 60 h sample of weekday afternoon television, there were 1893 advertisements, of which 483 were for food products or retailers. After applying the NP model, 66 % of these were classified as advertising high-fat, high-salt and high-sugar (HFSS) foods; 28 % were classified as advertising non-HFSS foods; and the remaining 2 % were unclassifiable. More than half (53 %) of the HFSS food advertisements were for 'mixed meal' items promoted by major fast-food franchises. The advertising of non-HFSS food was sparse, covering a narrow range of food groups, with no advertisements for fresh fruit or vegetables. Despite the NP model having some design limitations in classifying real-world televised food advertisements, it was easily applied to this sample and could clearly identify HFSS products. Policy makers who do not wish to completely restrict food advertising to children outright should consider using this NP model for regulating food advertising.

  11. A Hidden Markov Movement Model for rapidly identifying behavioral states from animal tracks

    DEFF Research Database (Denmark)

    Whoriskey, Kim; Auger-Méthé, Marie; Albertsen, Christoffer Moesgaard

    2017-01-01

    1. Electronic telemetry is frequently used to document animal movement through time. Methods that can identify underlying behaviors driving specific movement patterns can help us understand how and why animals use available space, thereby aiding conservation and management efforts. For aquatic....... 2. We developed a new Hidden Markov Model (HMM) for identifying behavioral states from animal tracks with negligible error, which we called the Hidden Markov Movement Model (HMMM). We implemented as the basis for the HMMM the process equation of the DCRWS, but we used the method of maximum...... animal tracking data with significant measurement error, a Bayesian state-space model called the first-Difference Correlated Random Walk with Switching (DCRWS) has often been used for this purpose. However, for aquatic animals, highly accurate tracking data of animal movement are now becoming more common...

  12. Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal – a case study from health science [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Heidi Holst Madsen

    2016-09-01

    Full Text Available Unique identifiers (UID are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case with publications from the health sciences. We evaluate the matching process based on information about coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match keys. We analyze this information to detect errors, if any, in the matching process. As an example we also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication.  The objective is addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI, incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication. The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of

  13. Using cloud models of heartbeats as the entity identifier to secure mobile devices.

    Science.gov (United States)

    Fu, Donglai; Liu, Yanhua

    2017-01-01

    Mobile devices are extensively used to store more private and often sensitive information. Therefore, it is important to protect them against unauthorised access. Authentication ensures that authorised users can use mobile devices. However, traditional authentication methods, such as numerical or graphic passwords, are vulnerable to passive attacks. For example, an adversary can steal the password by snooping from a shorter distance. To avoid these problems, this study presents a biometric approach that uses cloud models of heartbeats as the entity identifier to secure mobile devices. Here, it is identified that these concepts including cloud model or cloud have nothing to do with cloud computing. The cloud model appearing in the study is the cognitive model. In the proposed method, heartbeats are collected by two ECG electrodes that are connected to one mobile device. The backward normal cloud generator is used to generate ECG standard cloud models characterising the heartbeat template. When a user tries to have access to their mobile device, cloud models regenerated by fresh heartbeats will be compared with ECG standard cloud models to determine if the current user can use this mobile device. This authentication method was evaluated from three aspects including accuracy, authentication time and energy consumption. The proposed method gives 86.04% of true acceptance rate with 2.73% of false acceptance rate. One authentication can be done in 6s, and this processing consumes about 2000 mW of power.

  14. Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.

    Directory of Open Access Journals (Sweden)

    William R Swindell

    Full Text Available Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1. While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.

  15. Convective moisture adjustment time scale as a key factor in regulating model amplitude of the Madden-Julian Oscillation

    Science.gov (United States)

    Jiang, Xianan; Zhao, Ming; Maloney, Eric D.; Waliser, Duane E.

    2016-10-01

    Despite its pronounced impacts on weather extremes worldwide, the Madden-Julian Oscillation (MJO) remains poorly represented in climate models. Here we present findings that point to some necessary ingredients to produce a strong MJO amplitude in a large set of model simulations from a recent model intercomparison project. While surface flux and radiative heating anomalies are considered important for amplifying the MJO, their strength per unit MJO precipitation anomaly is found to be negatively correlated to MJO amplitude across these multimodel simulations. However, model MJO amplitude is found to be closely tied to a model's convective moisture adjustment time scale, a measure of how rapidly precipitation must increase to remove excess column water vapor, or alternately the efficiency of surface precipitation generation per unit column water vapor anomaly. These findings provide critical insights into key model processes for the MJO and pinpoint a direction for improved model representation of the MJO.

  16. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Directory of Open Access Journals (Sweden)

    Haitao Guo

    2017-01-01

    Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

  17. Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

    Directory of Open Access Journals (Sweden)

    Baker Syed

    2011-01-01

    Full Text Available Abstract In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF, rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison.

  18. Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models.

    Science.gov (United States)

    Baker, Syed Murtuza; Poskar, C Hart; Junker, Björn H

    2011-10-11

    In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF), rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison.

  19. Realtime Prediction in Disturbed Landscapes: Identifying Highest Priority Disturbance Characteristics Impacting Streamflow Response in a CONUS-Scale Operational Model

    Science.gov (United States)

    Dugger, A. L.; Gochis, D. J.; Yu, W.; McCreight, J. L.; Barlage, M. J.

    2015-12-01

    The "next generation" of hydrologic prediction systems - targeting unified, process-based, real-time prediction of the total water cycle - bring with them an increased need for real-time land surface characterization. Climatologically-derived estimates may perform well under stationary conditions, however disturbance can significantly alter hydrologic behavior and may be poorly represented by mean historical conditions. Fortunately, remote sensing and on-the-ground observation networks are collecting snapshots of these land characteristics over an increasing fraction of the globe. Given the computing constraints of operating a large-domain, real-time prediction system, to take advantage of these data streams we need a way to prioritize which landscape characteristics are most important to hydrologic prediction post-disturbance. To address this need, we setup a model experiment over the contiguous US using the community WRF-Hydro system with the NoahMP land surface model to assess the value of incorporating various aspects of disturbed landscapes into a real-time streamflow prediction model. WRF-Hydro will serve as the initial operational model for the US National Weather Service's new national water prediction effort, so use of WRF-Hydro allows us to leverage both an existing CONUS-scale model implementation and a short research-to-operations path. We first identify USGS GAGES-II basins that experienced more than 25% forest loss between 2000 and 2013. Based on basin disturbance type, geophysical setting, and climate regime, we formulate a conceptual model of which "disturbed" landscape characteristics we expect to dominate streamflow response. We test our conceptual model using WRF-Hydro by modeling a baseline (no disturbance) case, and then bringing in empirically-derived model state shifts representing key disturbance characteristics (e.g., leaf area index, rooting depth, overland roughness, surface detention). For each state update and each basin, we quantify

  20. Application of the Sea-Level Affecting Marshes Model (SLAMM 6) to Cedar Keys NWR

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This Sea Level Affecting Marshes Model (SLAMM) report presents a model for projecting the effects of sea-level rise on coastal marshes and related habitats on Cedar...

  1. THE CHALLENGE OF MEASURING FINANCIAL STRESS. CASE STUDY FOR IDENTIFYING THE MACROECONOMIC TRIGGERS OF FINANCIAL CRISIS WITH PANEL DATA MODELS

    Directory of Open Access Journals (Sweden)

    Smaranda CIMPOERU

    2015-08-01

    Full Text Available Measuring financial stress is a key research issue that has gained a lot of interest in the years following the extreme events from 2007. Although a lot of models were used for assessing and measuring financial stress, none of the managed to forecast the global crisis from 2007. We can identify three generation of models plus the approach of measuring the probability of a crisis with financial stress indexes. In our paper, we review briefly the most important approaches in measuring financial stress from the specialty literature and we propose a case study for European countries. We apply a logistic regression model for panel data, using macroeconomic indicators with the goal of finding the most important triggers for a financial crisis or otherwise said, the early warning signals of a crisis. We obtain very good accuracy of the proposed model (85% and the results are of great importance for policy makers and also for researchers. The study highly contributes to the specialty literature, considering that it is the first early warning system developed on macroeconomic indicators only for European advanced and emerging economies. Moreover, it includes in the analysis a period of five year following 2007.

  2. Identifying Key Variables in Intercultural Interaction.

    Science.gov (United States)

    1983-05-15

    campus or at sight of sojourn Size of college ( Selltiz , 1956) Presence of superordinate goals (Brislin, 1981) Appropriateness of work in host country to...adaptation. Itatinal Jginal .. I klI20n 3(1): 15-47. Schram, W., ed. 1960. M= Coommcations, 2nd ed. Urbana: University of Illinois Press. Selltiz , C

  3. Identifying strategy use in category learning tasks: a case for more diagnostic data and models.

    Science.gov (United States)

    Donkin, Chris; Newell, Ben R; Kalish, Mike; Dunn, John C; Nosofsky, Robert M

    2015-07-01

    The strength of conclusions about the adoption of different categorization strategies-and their implications for theories about the cognitive and neural bases of category learning-depend heavily on the techniques for identifying strategy use. We examine performance in an often-used "information-integration" category structure and demonstrate that strategy identification is affected markedly by the range of models under consideration, the type of data collected, and model-selection techniques. We use a set of 27 potential models that represent alternative rule-based and information-integration categorization strategies. Our experimental paradigm includes the presentation of nonreinforced transfer stimuli that improve one's ability to discriminate among the predictions of alternative models. Our model-selection techniques incorporate uncertainty in the identification of individuals as either rule-based or information-integration strategy users. Based on this analysis we identify 48% of participants as unequivocally using an information-integration strategy. However, adopting the standard practice of using a restricted set of models, restricted data, and ignoring the degree of support for a particular strategy, we would typically conclude that 89% of participants used an information-integration strategy. We discuss the implications of potentially erroneous strategy identification for the security of conclusions about the categorization capabilities of various participant and patient groups.

  4. A study of key features of the RAE atmospheric turbulence model

    Science.gov (United States)

    Jewell, W. F.; Heffley, R. K.

    1978-01-01

    A complex atmospheric turbulence model for use in aircraft simulation is analyzed in terms of its temporal, spectral, and statistical characteristics. First, a direct comparison was made between cases of the RAE model and the more conventional Dryden turbulence model. Next the control parameters of the RAE model were systematically varied and the effects noted. The RAE model was found to possess a high degree of flexibility in its characteristics, but the individual control parameters are cross-coupled in terms of their effect on various measures of intensity, bandwidth, and probability distribution.

  5. An overview of mice models: a key for understanding subtypes of mania

    Directory of Open Access Journals (Sweden)

    Jorge Mauricio Cuartas Arias

    2016-09-01

    Full Text Available Animal models have been broadly used in the study of pathophysiology and molecular and neurochemical pathways in neuropsychiatric diseases. Different approaches have used both consanguineous and non-consanguineous mice models to model behavioral patterns associated with the maniac spectrum. However, the disadvantages of validating clinical and experimental protocols have hindered the replication of these studies. In this article, the advantages and disadvantages of using consanguineous lines and non-consanguineous stocks in mice animal models for the study of mania and its subtypes are discussed. Additionally, new experimental alternatives to advance the pathogenesis and pharmacogenetics of mania using animal models are proposed and analyzed.

  6. A Modeling methodology for NoSQL Key-Value databases

    Directory of Open Access Journals (Sweden)

    Gerardo ROSSEL

    2017-08-01

    Full Text Available In recent years, there has been an increasing interest in the field of non-relational databases. However, far too little attention has been paid to design methodology. Key-value data stores are an important component of a class of non-relational technologies that are grouped under the name of NoSQL databases. The aim of this paper is to propose a design methodology for this type of database that allows overcoming the limitations of the traditional techniques. The proposed methodology leads to a clean design that also allows for better data management and consistency.

  7. Capricious Cables: Understanding the Key Concepts in Transmission Expansion Planning and Its Models

    Energy Technology Data Exchange (ETDEWEB)

    Donohoo, P.; Milligan, M.

    2014-06-01

    The extra-high-voltage transmission network is the bulk transport network of the electric power system. To understand how the future power system may react to planning decisions today, wide-area transmission models are increasingly used to aid decision makers and stakeholders. The goal of this work is to illuminate these models for a broader audience that may include policy makers or relative newcomers to the field of transmission planning. This paper explains the basic transmission expansion planning model formulation. It highlights six of the major simplifications made in transmission expansion planning models and the resulting need to contextualize model results using knowledge from other models and knowledge not captured in the modeling process.

  8. A state space transformation can yield identifiable models for tracer kinetic studies with enrichment data.

    Science.gov (United States)

    Ramakrishnan, Rajasekhar; Ramakrishnan, Janak D

    2010-11-01

    Tracer studies are analyzed almost universally by multicompartmental models where the state variables are tracer amounts or activities in the different pools. The model parameters are rate constants, defined naturally by expressing fluxes as fractions of the source pools. We consider an alternative state space with tracer enrichments or specific activities as the state variables, with the rate constants redefined by expressing fluxes as fractions of the destination pools. Although the redefinition may seem unphysiological, the commonly computed fractional synthetic rate actually expresses synthetic flux as a fraction of the product mass (destination pool). We show that, for a variety of structures, provided the structure is linear and stationary, the model in the enrichment state space has fewer parameters than that in the activities state space, and is hence better both to study identifiability and to estimate parameters. The superiority of enrichment modeling is shown for structures where activity model unidentifiability is caused by multiple exit pathways; on the other hand, with a single exit pathway but with multiple untraced entry pathways, activity modeling is shown to be superior. With the present-day emphasis on mass isotopes, the tracer in human studies is often of a precursor, labeling most or all entry pathways. It is shown that for these tracer studies, models in the activities state space are always unidentifiable when there are multiple exit pathways, even if the enrichment in every pool is observed; on the other hand, the corresponding models in the enrichment state space have fewer parameters and are more often identifiable. Our results suggest that studies with labeled precursors are modeled best with enrichments.

  9. Predictive modeling using a nationally representative database to identify patients at risk of developing microalbuminuria.

    Science.gov (United States)

    Villa-Zapata, Lorenzo; Warholak, Terri; Slack, Marion; Malone, Daniel; Murcko, Anita; Runger, George; Levengood, Michael

    2016-02-01

    Predictive models allow clinicians to identify higher- and lower-risk patients and make targeted treatment decisions. Microalbuminuria (MA) is a condition whose presence is understood to be an early marker for cardiovascular disease. The aims of this study were to develop a patient data-driven predictive model and a risk-score assessment to improve the identification of MA. The 2007-2008 National Health and Nutrition Examination Survey (NHANES) was utilized to create a predictive model. The dataset was split into thirds; one-third was used to develop the model, while the other two-thirds were utilized for internal validation. The 2012-2013 NHANES was used as an external validation database. Multivariate logistic regression was performed to create the model. Performance was evaluated using three criteria: (1) receiver operating characteristic curves; (2) pseudo-R (2) values; and (3) goodness of fit (Hosmer-Lemeshow). The model was then used to develop a risk-score chart. A model was developed using variables for which there was a significant relationship. Variables included were systolic blood pressure, fasting glucose, C-reactive protein, blood urea nitrogen, and alcohol consumption. The model performed well, and no significant differences were observed when utilized in the validation datasets. A risk score was developed, and the probability of developing MA for each score was calculated. The predictive model provides new evidence about variables related with MA and may be used by clinicians to identify at-risk patients and to tailor treatment. The risk score developed may allow clinicians to measure a patient's MA risk.

  10. A Bayesian Network Based Global Sensitivity Analysis Method for Identifying Dominant Processes in a Multi-physics Model

    Science.gov (United States)

    Dai, H.; Chen, X.; Ye, M.; Song, X.; Zachara, J. M.

    2016-12-01

    Sensitivity analysis has been an important tool in groundwater modeling to identify the influential parameters. Among various sensitivity analysis methods, the variance-based global sensitivity analysis has gained popularity for its model independence characteristic and capability of providing accurate sensitivity measurements. However, the conventional variance-based method only considers uncertainty contribution of single model parameters. In this research, we extended the variance-based method to consider more uncertainty sources and developed a new framework to allow flexible combinations of different uncertainty components. We decompose the uncertainty sources into a hierarchical three-layer structure: scenario, model and parametric. Furthermore, each layer of uncertainty source is capable of containing multiple components. An uncertainty and sensitivity analysis framework was then constructed following this three-layer structure using Bayesian network. Different uncertainty components are represented as uncertain nodes in this network. Through the framework, variance-based sensitivity analysis can be implemented with great flexibility of using different grouping strategies for uncertainty components. The variance-based sensitivity analysis thus is improved to be able to investigate the importance of an extended range of uncertainty sources: scenario, model, and other different combinations of uncertainty components which can represent certain key model system processes (e.g., groundwater recharge process, flow reactive transport process). For test and demonstration purposes, the developed methodology was implemented into a test case of real-world groundwater reactive transport modeling with various uncertainty sources. The results demonstrate that the new sensitivity analysis method is able to estimate accurate importance measurements for any uncertainty sources which were formed by different combinations of uncertainty components. The new methodology can

  11. A Study of Scientometric Methods to Identify Emerging Technologies via Modeling of Milestones

    Energy Technology Data Exchange (ETDEWEB)

    Abercrombie, Robert K [ORNL; Udoeyop, Akaninyene W [ORNL; Schlicher, Bob G [ORNL

    2012-01-01

    This work examines a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, patents, news archives, and online mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain we investigated.

  12. Characteristics of evolving models of care for arthritis: A key informant study

    OpenAIRE

    Veinot Paula; MacKay Crystal; Badley Elizabeth M

    2008-01-01

    Abstract Background The burden of arthritis is increasing in the face of diminishing health human resources to deliver care. In response, innovative models of care delivery are developing to facilitate access to quality care. Most models have developed in response to local needs with limited evaluation. The primary objective of this study is to a) examine the range of models of care that deliver specialist services using a medical/surgical specialist and at least one other health care provide...

  13. Identifying At-Risk Employees: Modeling Psychosocial Precursors of Potential Insider Threats

    Energy Technology Data Exchange (ETDEWEB)

    Greitzer, Frank L.; Kangas, Lars J.; Noonan, Christine F.; Dalton, Angela C.; Hohimer, Ryan E.

    2012-01-04

    In many insider crimes, managers and other coworkers observed that the offenders had exhibited signs of stress, disgruntlement, or other issues, but no alarms were raised. Barriers to using such psychosocial indicators include the inability to recognize the signs and the failure to record the behaviors so that they can be assessed. A psychosocial model was developed to assess an employee's behavior associated with an increased risk of insider abuse. The model is based on case studies and research literature on factors/correlates associated with precursor behavioral manifestations of individuals committing insider crimes. To test the model's agreement with human resources and management professionals, we conducted an experiment with positive results. If implemented in an operational setting, the model would be part of a set of management tools for employee assessment to identify employees who pose a greater insider threat.

  14. Expansion of the Kano model to identify relevant customer segments and functional requirements

    DEFF Research Database (Denmark)

    Atlason, Reynir Smari; Stefansson, Arnaldur Smari; Wietz, Miriam

    2017-01-01

    or a service. A current limitation of the Kano model is that it does not allow developers to visualise which combined sets of FRs would provide the highest satisfaction between different customer segments. In this paper, a stepwise method to address this particular shortcoming is presented. First......The Kano model of customer satisfaction has been widely used to analyse perceived needs of customers. The model provides product developers valuable information about if, and then how much a given functional requirement (FR) will impact customer satisfaction if implemented within a product, system...... are identified. At last, the functions of the chosen segments with the smallest interval, define the FRs appealing to the biggest target group. The proposed extension to the model should assist product developers within various fields to more effectively evaluate which FRs should be implemented when considering...

  15. Model of areas for identifying risks influencing the compliance of technological processes and products

    Science.gov (United States)

    Misztal, A.; Belu, N.

    2016-08-01

    Operation of every company is associated with the risk of interfering with proper performance of its fundamental processes. This risk is associated with various internal areas of the company, as well as the environment in which it operates. From the point of view of ensuring compliance of the course of specific technological processes and, consequently, product conformity with requirements, it is important to identify these threats and eliminate or reduce the risk of their occurrence. The purpose of this article is to present a model of areas of identifying risk affecting the compliance of processes and products, which is based on multiregional targeted monitoring of typical places of interference and risk management methods. The model is based on the verification of risk analyses carried out in small and medium-sized manufacturing companies in various industries..

  16. Discussion of using artificial neural nets to identify the well-test interpretation model

    Energy Technology Data Exchange (ETDEWEB)

    Yeung, K. (Univ. of Alberta, Edmonton, Alberta (Canada)); Chakrabarty, C. (Golder Associates, Nottingham (United Kingdom)); Wu, S. (Univ. of Melbourne (Australia))

    1994-09-01

    Use of artificial neural nets (ANN's) to identify noisy and apparently unrecognizable patterns is common for many real-world problems, ranging from applications such as speech recognition to stock market prediction. ANN approaches are often good candidates for recognizing patterns when rigid mathematical models do not exist or are insufficient to meet a full-scale identification requirement. Al-Kaabi and Lee's proposal of using ANN's to identify the well-test interpretation model is appropriate because well-test data is often highly nonlinear and noisy. The purpose of this discussion is to present some of the authors results in a similar study and to suggest a simple technique that would enhance the use of ANN's in Al-Kaabi and Lee's approach.

  17. Using genetic algorithm to learn neural network identifier for modeling gyro startup drift rate

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Studies the modeling of gyro startup drift rate from acquired experimental gyro startup drift rate data and the nonlinear dynamic models of gyro startup drift rate related temperature established by time-delay neural network which enables the gyro temperature drift rate to be compensated in the process of startup and the gyro instant startup to be implemented. And introduces an improved genetic algorithm to learn the weights of neural network identifier to avoid stacking into the local minimal value and achieve rapid convergence.

  18. A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

    Directory of Open Access Journals (Sweden)

    Warren D Anderson

    2017-07-01

    Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

  19. FRIGA, A New Approach To Identify Isotopes and Hypernuclei In N-Body Transport Models

    CERN Document Server

    Fèvre, A Le; Aichelin, J; Hartnack, Ch; Kireyev, V; Bratkovskaya, E

    2015-01-01

    We present a new algorithm to identify fragments in computer simulations of relativistic heavy ion collisions. It is based on the simulated annealing technique and can be applied to n-body transport models like the Quantum Molecular Dynamics. This new approach is able to predict isotope yields as well as hyper-nucleus production. In order to illustrate its predicting power, we confront this new method to experimental data, and show the sensitivity on the parameters which govern the cluster formation.

  20. GIS model for identifying urban areas vulnerable to noise pollution: case study

    Science.gov (United States)

    Bilaşco, Ştefan; Govor, Corina; Roşca, Sanda; Vescan, Iuliu; Filip, Sorin; Fodorean, Ioan

    2017-04-01

    The unprecedented expansion of the national car ownership over the last few years has been determined by economic growth and the need for the population and economic agents to reduce travel time in progressively expanding large urban centres. This has led to an increase in the level of road noise and a stronger impact on the quality of the environment. Noise pollution generated by means of transport represents one of the most important types of pollution with negative effects on a population's health in large urban areas. As a consequence, tolerable limits of sound intensity for the comfort of inhabitants have been determined worldwide and the generation of sound maps has been made compulsory in order to identify the vulnerable zones and to make recommendations how to decrease the negative impact on humans. In this context, the present study aims at presenting a GIS spatial analysis model-based methodology for identifying and mapping zones vulnerable to noise pollution. The developed GIS model is based on the analysis of all the components influencing sound propagation, represented as vector databases (points of sound intensity measurements, buildings, lands use, transport infrastructure), raster databases (DEM), and numerical databases (wind direction and speed, sound intensity). Secondly, the hourly changes (for representative hours) were analysed to identify the hotspots characterised by major traffic flows specific to rush hours. The validated results of the model are represented by GIS databases and useful maps for the local public administration to use as a source of information and in the process of making decisions.

  1. KEY TECHNIQUES OF MULTI-BODY MODELING OF OCCUPANT RESTRAINT SYSTEM OF VEHICLE SIDE IMPACT

    Institute of Scientific and Technical Information of China (English)

    ZHANG Junyuan; ZHANG Min; DING Rufang; QIU Shaobo; ZHANG Yu; LI Hongjian

    2006-01-01

    Based on multi-body dynamics, the simulation models of auto-side structures and occupant's dynamic responses are set up, using the occupant injury simulation software MADYMO3D. These models include auto-body structure, impact barrier, seat and dummy. Definitions of multi-body and joints and dynamics properties of joints based on FE combination models, of model setup are introduced. Kelvin element of MADYMO is introduced to show the force action between non-adjoining rigid bodies, too. Then all examples of the methods mentioned are given. By the comparison of simulation and real test, the contract curves between simulation and real test for main structures and biology mechanics properties of dummy are obtained. The result shows the accuracy and validity of the models.

  2. European Bilingual Models beyond "Lingua Franca": Key Findings from CLIL French Programs

    Science.gov (United States)

    Pérez, América; Lorenzo, Francisco; Pavón, Víctor

    2016-01-01

    Content and Language Integrated Learning (CLIL) has expanded all around the continent following European Council guidelines, favored by competence studies that identified educational systems as a strong determinant for second language gains and deficits. Over the years since the turn of the century, CLIL has gained the support of language policy…

  3. European Bilingual Models beyond "Lingua Franca": Key Findings from CLIL French Programs

    Science.gov (United States)

    Pérez, América; Lorenzo, Francisco; Pavón, Víctor

    2016-01-01

    Content and Language Integrated Learning (CLIL) has expanded all around the continent following European Council guidelines, favored by competence studies that identified educational systems as a strong determinant for second language gains and deficits. Over the years since the turn of the century, CLIL has gained the support of language policy…

  4. A computational technique to identify the optimal stiffness matrix for a discrete nuclear fuel assembly model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Nam-Gyu, E-mail: nkpark@knfc.co.kr [R and D Center, KEPCO Nuclear Fuel Co., LTD., 493 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Kyoung-Joo, E-mail: kyoungjoo@knfc.co.kr [R and D Center, KEPCO Nuclear Fuel Co., LTD., 493 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Kyoung-Hong, E-mail: kyounghong@knfc.co.kr [R and D Center, KEPCO Nuclear Fuel Co., LTD., 493 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Suh, Jung-Min, E-mail: jmsuh@knfc.co.kr [R and D Center, KEPCO Nuclear Fuel Co., LTD., 493 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)

    2013-02-15

    Highlights: ► An identification method of the optimal stiffness matrix for a fuel assembly structure is discussed. ► The least squares optimization method is introduced, and a closed form solution of the problem is derived. ► The method can be expanded to the system with the limited number of modes. ► Identification error due to the perturbed mode shape matrix is analyzed. ► Verification examples show that the proposed procedure leads to a reliable solution. -- Abstract: A reactor core structural model which is used to evaluate the structural integrity of the core contains nuclear fuel assembly models. Since the reactor core consists of many nuclear fuel assemblies, the use of a refined fuel assembly model leads to a considerable amount of computing time for performing nonlinear analyses such as the prediction of seismic induced vibration behaviors. The computational time could be reduced by replacing the detailed fuel assembly model with a simplified model that has fewer degrees of freedom, but the dynamic characteristics of the detailed model must be maintained in the simplified model. Such a model based on an optimal design method is proposed in this paper. That is, when a mass matrix and a mode shape matrix are given, the optimal stiffness matrix of a discrete fuel assembly model can be estimated by applying the least squares minimization method. The verification of the method is completed by comparing test results and simulation results. This paper shows that the simplified model's dynamic behaviors are quite similar to experimental results and that the suggested method is suitable for identifying reliable mathematical model for fuel assemblies.

  5. Data warehouse model for monitoring key performance indicators (KPIs) using goal oriented approach

    Science.gov (United States)

    Abdullah, Mohammed Thajeel; Ta'a, Azman; Bakar, Muhamad Shahbani Abu

    2016-08-01

    The growth and development of universities, just as other organizations, depend on their abilities to strategically plan and implement development blueprints which are in line with their vision and mission statements. The actualizations of these statements, which are often designed into goals and sub-goals and linked to their respective actors are better measured by defining key performance indicators (KPIs) of the university. The proposes ReGADaK, which is an extended the GRAnD approach highlights the facts, dimensions, attributes, measures and KPIs of the organization. The measures from the goal analysis of this unit serve as the basis of developing the related university's KPIs. The proposed data warehouse schema is evaluated through expert review, prototyping and usability evaluation. The findings from the evaluation processes suggest that the proposed data warehouse schema is suitable for monitoring the University's KPIs.

  6. An algorithmic calibration approach to identify globally optimal parameters for constraining the DayCent model

    Energy Technology Data Exchange (ETDEWEB)

    Rafique, Rashid; Kumar, Sandeep; Luo, Yiqi; Kiely, Gerard; Asrar, Ghassem R.

    2015-02-01

    he accurate calibration of complex biogeochemical models is essential for the robust estimation of soil greenhouse gases (GHG) as well as other environmental conditions and parameters that are used in research and policy decisions. DayCent is a popular biogeochemical model used both nationally and internationally for this purpose. Despite DayCent’s popularity, its complex parameter estimation is often based on experts’ knowledge which is somewhat subjective. In this study we used the inverse modelling parameter estimation software (PEST), to calibrate the DayCent model based on sensitivity and identifi- ability analysis. Using previously published N2 O and crop yield data as a basis of our calibration approach, we found that half of the 140 parameters used in this study were the primary drivers of calibration dif- ferences (i.e. the most sensitive) and the remaining parameters could not be identified given the data set and parameter ranges we used in this study. The post calibration results showed improvement over the pre-calibration parameter set based on, a decrease in residual differences 79% for N2O fluxes and 84% for crop yield, and an increase in coefficient of determination 63% for N2O fluxes and 72% for corn yield. The results of our study suggest that future studies need to better characterize germination tem- perature, number of degree-days and temperature dependency of plant growth; these processes were highly sensitive and could not be adequately constrained by the data used in our study. Furthermore, the sensitivity and identifiability analysis was helpful in providing deeper insight for important processes and associated parameters that can lead to further improvement in calibration of DayCent model.

  7. Prospective validation of a predictive model that identifies homeless people at risk of re-presentation to the emergency department.

    Science.gov (United States)

    Moore, Gaye; Hepworth, Graham; Weiland, Tracey; Manias, Elizabeth; Gerdtz, Marie Frances; Kelaher, Margaret; Dunt, David

    2012-02-01

    To prospectively evaluate the accuracy of a predictive model to identify homeless people at risk of representation to an emergency department. A prospective cohort analysis utilised one month of data from a Principal Referral Hospital in Melbourne, Australia. All visits involving people classified as homeless were included, excluding those who died. Homelessness was defined as living on the streets, in crisis accommodation, in boarding houses or residing in unstable housing. Rates of re-presentation, defined as the total number of visits to the same emergency department within 28 days of discharge from hospital, were measured. Performance of the risk screening tool was assessed by calculating sensitivity, specificity, positive and negative predictive values and likelihood ratios. Over the study period (April 1, 2009 to April 30, 2009), 3298 presentations from 2888 individuals were recorded. The homeless population accounted for 10% (n=327) of all visits and 7% (n=211) of all patients. A total of 90 (43%) homeless people re-presented to the emergency department. The predictive model included nine variables and achieved 98% (CI, 0.92-0.99) sensitivity and 66% (CI, 0.57-0.74) specificity. The positive predictive value was 68% and the negative predictive value was 98%. The positive likelihood ratio 2.9 (CI, 2.2-3.7) and the negative likelihood ratio was 0.03 (CI, 0.01-0.13). The high emergency department re-presentation rate for people who were homeless identifies unresolved psychosocial health needs. The emergency department remains a vital access point for homeless people, particularly after hours. The risk screening tool is key to identify medical and social aspects of a homeless patient's presentation to assist early identification and referral. Copyright © 2012 College of Emergency Nursing Australasia Ltd. Published by Elsevier Ltd. All rights reserved.

  8. Identifying regulational alterations in gene regulatory networks by state space representation of vector autoregressive models and variational annealing.

    Science.gov (United States)

    Kojima, Kaname; Imoto, Seiya; Yamaguchi, Rui; Fujita, André; Yamauchi, Mai; Gotoh, Noriko; Miyano, Satoru

    2012-01-01

    In the analysis of effects by cell treatment such as drug dosing, identifying changes on gene network structures between normal and treated cells is a key task. A possible way for identifying the changes is to compare structures of networks estimated from data on normal and treated cells separately. However, this approach usually fails to estimate accurate gene networks due to the limited length of time series data and measurement noise. Thus, approaches that identify changes on regulations by using time series data on both conditions in an efficient manner are demanded. We propose a new statistical approach that is based on the state space representation of the vector autoregressive model and estimates gene networks on two different conditions in order to identify changes on regulations between the conditions. In the mathematical model of our approach, hidden binary variables are newly introduced to indicate the presence of regulations on each condition. The use of the hidden binary variables enables an efficient data usage; data on both conditions are used for commonly existing regulations, while for condition specific regulations corresponding data are only applied. Also, the similarity of networks on two conditions is automatically considered from the design of the potential function for the hidden binary variables. For the estimation of the hidden binary variables, we derive a new variational annealing method that searches the configuration of the binary variables maximizing the marginal likelihood. For the performance evaluation, we use time series data from two topologically similar synthetic networks, and confirm that our proposed approach estimates commonly existing regulations as well as changes on regulations with higher coverage and precision than other existing approaches in almost all the experimental settings. For a real data application, our proposed approach is applied to time series data from normal Human lung cells and Human lung cells treated by

  9. Markov Mixed Effects Modeling Using Electronic Adherence Monitoring Records Identifies Influential Covariates to HIV Preexposure Prophylaxis.

    Science.gov (United States)

    Madrasi, Kumpal; Chaturvedula, Ayyappa; Haberer, Jessica E; Sale, Mark; Fossler, Michael J; Bangsberg, David; Baeten, Jared M; Celum, Connie; Hendrix, Craig W

    2016-12-06

    Adherence is a major factor in the effectiveness of preexposure prophylaxis (PrEP) for HIV prevention. Modeling patterns of adherence helps to identify influential covariates of different types of adherence as well as to enable clinical trial simulation so that appropriate interventions can be developed. We developed a Markov mixed-effects model to understand the covariates influencing adherence patterns to daily oral PrEP. Electronic adherence records (date and time of medication bottle cap opening) from the Partners PrEP ancillary adherence study with a total of 1147 subjects were used. This study included once-daily dosing regimens of placebo, oral tenofovir disoproxil fumarate (TDF), and TDF in combination with emtricitabine (FTC), administered to HIV-uninfected members of serodiscordant couples. One-coin and first- to third-order Markov models were fit to the data using NONMEM(®) 7.2. Model selection criteria included objective function value (OFV), Akaike information criterion (AIC), visual predictive checks, and posterior predictive checks. Covariates were included based on forward addition (α = 0.05) and backward elimination (α = 0.001). Markov models better described the data than 1-coin models. A third-order Markov model gave the lowest OFV and AIC, but the simpler first-order model was used for covariate model building because no additional benefit on prediction of target measures was observed for higher-order models. Female sex and older age had a positive impact on adherence, whereas Sundays, sexual abstinence, and sex with a partner other than the study partner had a negative impact on adherence. Our findings suggest adherence interventions should consider the role of these factors.

  10. Modelling of sea salt concentrations over Europe: key uncertainties and comparison with observations

    Directory of Open Access Journals (Sweden)

    S. Tsyro

    2011-10-01

    Full Text Available Sea salt aerosol can significantly affect the air quality. Sea salt can cause enhanced concentrations of particulate matter and change particle chemical composition, in particular in coastal areas, and therefore should be accounted for in air quality modelling. We have used an EMEP Unified model to calculate sea salt concentrations and depositions over Europe, focusing on studying the effects of uncertainties in sea salt production and lifetime on calculation results. Model calculations of sea salt have been compared with EMEP observations of sodium concentrations in air and precipitation for a four year period, from 2004 to 2007, including size (fine/coarse resolved EMEP intensive measurements in 2006 and 2007. In the presented calculations, sodium air concentrations are between 8% and 46% overestimated, whereas concentrations in precipitation are systematically underestimated by 65–70% for years 2004–2007. A series of model tests have been performed to investigate the reasons for this underestimation, but further studies are needed. The model is found to reproduce the spatial distribution of Na+ in air and precipitation over Europe fairly well, and to capture most of sea salt episodes. The paper presents the main findings from a series of tests in which we compare several different sea spray source functions and also look at the effects of meteorological input and the efficiency of removal processes on calculated sea salt concentrations. Finally, sea salt calculations with the EMEP model have been compared with results from the SILAM model and observations for 2007. While the models produce quite close results for Na+ at the majority of 26 measurement sites, discrepancies in terms of bias and temporal correlation are also found. Those differences are believed to occur due to differences in the representation of source function and size distribution of sea salt aerosol, different meteorology used for model runs and the

  11. Impact of Hybrid Intelligent Computing in Identifying Constructive Weather Parameters for Modeling Effective Rainfall Prediction

    Directory of Open Access Journals (Sweden)

    M. Sudha

    2015-12-01

    Full Text Available Uncertain atmosphere is a prevalent factor affecting the existing prediction approaches. Rough set and fuzzy set theories as proposed by Pawlak and Zadeh have become an effective tool for handling vagueness and fuzziness in the real world scenarios. This research work describes the impact of Hybrid Intelligent System (HIS for strategic decision support in meteorology. In this research a novel exhaustive search based Rough set reduct Selection using Genetic Algorithm (RSGA is introduced to identify the significant input feature subset. The proposed model could identify the most effective weather parameters efficiently than other existing input techniques. In the model evaluation phase two adaptive techniques were constructed and investigated. The proposed Artificial Neural Network based on Back Propagation learning (ANN-BP and Adaptive Neuro Fuzzy Inference System (ANFIS was compared with existing Fuzzy Unordered Rule Induction Algorithm (FURIA, Structural Learning Algorithm on Vague Environment (SLAVE and Particle Swarm OPtimization (PSO. The proposed rainfall prediction models outperformed when trained with the input generated using RSGA. A meticulous comparison of the performance indicates ANN-BP model as a suitable HIS for effective rainfall prediction. The ANN-BP achieved 97.46% accuracy with a nominal misclassification rate of 0.0254 %.

  12. Modelling succession of key resource harvesting traits of mixotrophic plankton populations

    DEFF Research Database (Denmark)

    Berge, Terje; Chakraborty, Subhendu; Hansen, Per Juel;

    2016-01-01

    Unicellular eukaryotes make up the base of the ocean food web and exist as a continuum in trophic strategy from pure heterotrophy (phagotrophic zooplankton) to pure photoautotrophy (‘phytoplankton’), with a dominance of mixotrophic organisms combining both strategies. Here we formulate a trait...... in the spring and increased phagotrophy during the summer, reflecting general seasonal succession patterns of temperate waters. Our trait-based model presents a simple and general approach for the inclusion of mixotrophy, succession and evolution in ecosystem models....

  13. Key Parameters for the Inconsistencies of the Incoming Solar Radiation Boundary Condition in Global Modeling

    Science.gov (United States)

    Tsushima, Yoko; Raschke, Ehrhard; Kinne, Stefan; Abe-Ouchi, Ayako; Bakan, Stefan; Emori, Seita; Giorgetta, Marco; Kopp, Greg; Saito, Fuyuki; Timm, Oliver; Wild, Martin

    2009-03-01

    By a comparison of the insolation, computed by 19 different climate models for the International Panel on Climate Change Fourth Assessment Report (IPCC-AR4) test period from 1980 to 1999, it is shown that those models used different values for the solar constant and for its solar cycle variations. Meridional profiles for the monthly incoming radiation displayed diversities of up to ±10 Wm-2, especially during the transient seasons. Sensitivity studies with minima and maxima for the assumed orbital parameters of the Earth show almost no change. However, the different temporal partitioning for onset and length of individual months based on different calendars (e.g. simplifications such as 30 days for each month) results in the difference in the insolation, which is strongly resemble in amount and in zonal pattern the observed diversity of the insolation in IPCC models. Contributing error sources are also different assumptions for cut-off angles at low sun-elevations and differences in increment-difference during spatial and temporal integrations. Possible impacts of these contributing errors in climate modeling are investigated within a coupled ocean-atmosphere model. It is found that monthly radiative fluxes, humidity, and temperature have a difference between the two vernal equinox experiments. Although it remained within the magnitude of the inter-model difference, the difference is systematic.

  14. Modelling the exposure of wildlife to radiation: key findings and activities of IAEA working groups

    Energy Technology Data Exchange (ETDEWEB)

    Beresford, Nicholas A. [NERC Centre for Ecology and Hydrology, Lancaster Environment Center, Library Av., Bailrigg, Lancaster, LA1 4AP (United Kingdom); School of Environment and Life Sciences, University of Salford, Manchester, M4 4WT (United Kingdom); Vives i Batlle, Jordi; Vandenhove, Hildegarde [Belgian Nuclear Research Centre, Belgian Nuclear Research Centre, Boeretang 200, 2400 Mol (Belgium); Beaugelin-Seiller, Karine [Institut de Radioprotection et de Surete Nucleaire (IRSN), PRP-ENV, SERIS, LM2E, Cadarache (France); Johansen, Mathew P. [ANSTO Australian Nuclear Science and Technology Organisation, New Illawarra Rd, Menai, NSW (Australia); Goulet, Richard [Canadian Nuclear Safety Commission, Environmental Risk Assessment Division, 280 Slater, Ottawa, K1A0H3 (Canada); Wood, Michael D. [School of Environment and Life Sciences, University of Salford, Manchester, M4 4WT (United Kingdom); Ruedig, Elizabeth [Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins (United States); Stark, Karolina; Bradshaw, Clare [Department of Ecology, Environment and Plant Sciences, Stockholm University, SE-10691 (Sweden); Andersson, Pal [Swedish Radiation Safety Authority, SE-171 16, Stockholm (Sweden); Copplestone, David [Biological and Environmental Sciences, University of Stirling, Stirling, FK9 4LA (United Kingdom); Yankovich, Tamara L.; Fesenko, Sergey [International Atomic Energy Agency, Vienna International Centre, 1400, Vienna (Austria)

    2014-07-01

    In total, participants from 14 countries, representing 19 organisations, actively participated in the model application/inter-comparison activities of the IAEA's EMRAS II programme Biota Modelling Group. A range of models/approaches were used by participants (e.g. the ERICA Tool, RESRAD-BIOTA, the ICRP Framework). The agreed objectives of the group were: 'To improve Member State's capabilities for protection of the environment by comparing and validating models being used, or developed, for biota dose assessment (that may be used) as part of the regulatory process of licensing and compliance monitoring of authorised releases of radionuclides.' The activities of the group, the findings of which will be described, included: - An assessment of the predicted unweighted absorbed dose rates for 74 radionuclides estimated by 10 approaches for five of the ICRPs Reference Animal and Plant geometries assuming 1 Bq per unit organism or media. - Modelling the effect of heterogeneous distributions of radionuclides in sediment profiles on the estimated exposure of organisms. - Model prediction - field data comparisons for freshwater ecosystems in a uranium mining area and a number of wetland environments. - An evaluation of the application of available models to a scenario considering radioactive waste buried in shallow trenches. - Estimating the contribution of {sup 235}U to dose rates in freshwater environments. - Evaluation of the factors contributing to variation in modelling results. The work of the group continues within the framework of the IAEA's MODARIA programme, which was initiated in 2012. The work plan of the MODARIA working group has largely been defined by the findings of the previous EMRAS programme. On-going activities of the working group, which will be described, include the development of a database of dynamic parameters for wildlife dose assessment and exercises involving modelling the exposure of organisms in the marine coastal

  15. Quantum key management

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

    2016-11-29

    Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

  16. Quantum key management

    Science.gov (United States)

    Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

    2016-11-29

    Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

  17. Identifying Multiple Levels of Discussion-Based Teaching Strategies for Constructing Scientific Models

    Science.gov (United States)

    Williams, Grant; Clement, John

    2015-01-01

    This study sought to identify specific types of discussion-based strategies that two successful high school physics teachers using a model-based approach utilized in attempting to foster students' construction of explanatory models for scientific concepts. We found evidence that, in addition to previously documented dialogical strategies that teachers utilize to engage students in effectively communicating their scientific ideas in class, there is a second level of more cognitively focused model-construction-supporting strategies that these teachers utilized in attempting to foster students' learning. A further distinction between macro and micro strategy levels within the set of cognitive strategies is proposed. The relationships between the resulting three levels of strategies are portrayed in a diagramming system that tracks discussions over time. The study attempts to contribute to a clearer understanding of how discussion-leading strategies may be used to scaffold the development of conceptual understanding.

  18. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna

    2015-01-01

    Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...... based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted...... antimetabolites using two cell lines with different phenotypic origins, and found that it is effective in inhibiting the growth of these cell lines. Using immunohistochemistry, we also showed high or moderate expression levels of proteins targeted by the validated antimetabolite. Identified anti-growth factors...

  19. Identifying best existing practice for characterization modeling in life cycle impact assessment

    DEFF Research Database (Denmark)

    Hauschild, Michael Zwicky; Goedkoop, Mark; Guinée, Jeroen

    2013-01-01

    Purpose: Life cycle impact assessment (LCIA) is a field of active development. The last decade has seen prolific publication of new impact assessment methods covering many different impact categories and providing characterization factors that often deviate from each other for the same substance...... continents and still support aggregation of impact scores over the whole life cycle. For the impact categories human toxicity and ecotoxicity, we are now able to recommend a model, but the number of chemical substances in common use is so high that there is a need to address the substance data shortage...... was performed for the Joint Research Centre of the European Commission (JRC). Methods Existing LCIA methods were collected and their individual characterization models identified at both midpoint and endpoint levels and supplemented with other environmental models of potential use for LCIA. No new developments...

  20. A 3-D mathematical model to identify organ-specific risks in rats during thermal stress.

    Science.gov (United States)

    Rakesh, Vineet; Stallings, Jonathan D; Helwig, Bryan G; Leon, Lisa R; Jackson, David A; Reifman, Jaques

    2013-12-01

    Early prediction of the adverse outcomes associated with heat stress is critical for effective management and mitigation of injury, which may sometimes lead to extreme undesirable clinical conditions, such as multiorgan dysfunction syndrome and death. Here, we developed a computational model to predict the spatiotemporal temperature distribution in a rat exposed to heat stress in an attempt to understand the correlation between heat load and differential organ dysfunction. The model includes a three-dimensional representation of the rat anatomy obtained from medical imaging and incorporates the key mechanisms of heat transfer during thermoregulation. We formulated a novel approach to estimate blood temperature by accounting for blood mixing from the different organs and to estimate the effects of the circadian rhythm in body temperature by considering day-night variations in metabolic heat generation and blood perfusion. We validated the model using in vivo core temperature measurements in control and heat-stressed rats and other published experimental data. The model predictions were within 1 SD of the measured data. The liver demonstrated the greatest susceptibility to heat stress, with the maximum temperature reaching 2°C higher than the measured core temperature and 95% of its volume exceeding the targeted experimental core temperature. Other organs also attained temperatures greater than the core temperature, illustrating the need to monitor multiple organs during heat stress. The model facilitates the identification of organ-specific risks during heat stress and has the potential to aid in the development of improved clinical strategies for thermal-injury prevention and management.

  1. New drug candidates for liposomal delivery identified by computer modeling of liposomes' remote loading and leakage.

    Science.gov (United States)

    Cern, Ahuva; Marcus, David; Tropsha, Alexander; Barenholz, Yechezkel; Goldblum, Amiram

    2017-02-16

    Remote drug loading into nano-liposomes is in most cases the best method for achieving high concentrations of active pharmaceutical ingredients (API) per nano-liposome that enable therapeutically viable API-loaded nano-liposomes, referred to as nano-drugs. This approach also enables controlled drug release. Recently, we constructed computational models to identify APIs that can achieve the desired high concentrations in nano-liposomes by remote loading. While those previous models included a broad spectrum of experimental conditions and dealt only with loading, here we reduced the scope to the molecular characteristics alone. We model and predict API suitability for nano-liposomal delivery by fixing the main experimental conditions: liposome lipid composition and size to be similar to those of Doxil® liposomes. On that basis, we add a prediction of drug leakage from the nano-liposomes during storage. The latter is critical for having pharmaceutically viable nano-drugs. The "load and leak" models were used to screen two large molecular databases in search of candidate APIs for delivery by nano-liposomes. The distribution of positive instances in both loading and leakage models was similar in the two databases screened. The screening process identified 667 molecules that were positives by both loading and leakage models (i.e., both high-loading and stable). Among them, 318 molecules received a high score in both properties and of these, 67 are FDA-approved drugs. This group of molecules, having diverse pharmacological activities, may be the basis for future liposomal drug development.

  2. Using growth mixture modeling to identify classes of sodium adherence in adults with heart failure.

    Science.gov (United States)

    Masterson Creber, Ruth; Lee, Christopher S; Lennie, Terry A; Topaz, Maxim; Riegel, Barbara

    2014-01-01

    The prevention of fluid retention is important to reduce hospitalizations in patients with heart failure (HF). Following a low-sodium diet helps to reduce fluid retention. The primary objective of this study was to use growth mixture modeling to identify distinct classes of sodium adherence-characterized by shared growth trajectories of objectively measured dietary sodium. The secondary objective was to identify patient-level determinants of the nonadherent trajectory. This was a secondary analysis of data collected from a prospective longitudinal study of 279 community-dwelling adults with previously or currently symptomatic HF. Growth mixture modeling was used to identify distinct trajectories of change in 24-hour urinary sodium excretion measured at 3 time points over 6 months. Logistic modeling was used to predict membership in observed trajectories. The sample was predominantly male (64%), had a mean age of 62 years, was functionally compromised (59% New York Heart Association class III), and had nonischemic HF etiology. Two distinct trajectories of sodium intake were identified and labeled adherent (66%) and nonadherent (34%) to low-sodium diet recommendations. Three predictors of the nonadherent trajectory were identified, confirming our previous mixed-effect analysis. Compared with being normal weight (body mass index obese was associated with a 4-fold incremental increase in the likelihood of being in the nonadherent trajectory (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.66-12.91; P < .002). Being younger than 65 years (OR, 4.66; 95% CI, 1.04-20.81; P = .044) or having diabetes (OR, 4.15; 95% CI, 1.29-13.40; P = .016) were both associated with more than 4 times the odds of being in the nonadherent urine sodium trajectory compared with being older than 65 years or not having diabetes, respectively. Two distinct trajectories of sodium intake were identified in patients with HF. The nonadherent trajectory was characterized by an elevated pattern

  3. Animal models of diabetic macrovascular complications: key players in the development of new therapeutic approaches.

    Science.gov (United States)

    Heinonen, Suvi E; Genové, Guillem; Bengtsson, Eva; Hübschle, Thomas; Åkesson, Lina; Hiss, Katrin; Benardeau, Agnes; Ylä-Herttuala, Seppo; Jönsson-Rylander, Ann-Cathrine; Gomez, Maria F

    2015-01-01

    Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease) and microvascular disorders leading to damage of the kidneys (nephropathy) and eyes (retinopathy). Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative), the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools) consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development.

  4. Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Suvi E. Heinonen

    2015-01-01

    Full Text Available Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease and microvascular disorders leading to damage of the kidneys (nephropathy and eyes (retinopathy. Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative, the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development.

  5. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Directory of Open Access Journals (Sweden)

    Carlos Pozo

    Full Text Available Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study

  6. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Science.gov (United States)

    Pozo, Carlos; Guillén-Gosálbez, Gonzalo; Sorribas, Albert; Jiménez, Laureano

    2012-01-01

    Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the

  7. Prognostic model for brain metastases from lung adenocarcinoma identified with epidermal growth factor receptor mutation status.

    Science.gov (United States)

    Li, Hongwei; Wang, Weili; Jia, Haixia; Lian, Jianhong; Cao, Jianzhong; Zhang, Xiaqin; Song, Xing; Jia, Sufang; Li, Zhengran; Cao, Xing; Zhou, Wei; Han, Songye; Yang, Weihua; Xi, Yanfen; Lian, Shenming

    2017-09-01

    Several indices have been developed to predict survival of brain metastases (BM) based on prognostic factors. However, such models were designed for general brain metastases from different kinds of cancers, and prognostic factors vary between cancers and histological subtypes. Recently, studies have indicated that epidermal growth factor receptor (EGFR) mutation status may be a potential prognostic biological factor in BM from lung adenocarcinoma. Thus, we sought to define the role of EGFR mutation in prognoses and introduce a prognostic model specific for BM from lung adenocarcinoma. Data of 256 patients with BM from lung adenocarcinoma identified with EGFR mutations were collected. Independent prognostic factors were confirmed using a Cox regression model. The new prognostic model was developed based on the results of multivariable analyses. The score of each factor was calculated by six-month survival. Prognostic groups were divided into low, medium, and high risk based on the total scores. The prediction ability of the new model was compared to the three existing models. EGFR mutation and Karnofsky performance status were independent prognostic factors and were thus integrated into the new prognostic model. The new model was superior to the three other scoring systems regarding the prediction of three, six, and 12-month survival by pairwise comparison of the area under the curve. Our proposed prognostic model specific for BM from lung adenocarcinoma incorporating EGFR mutation status was valid in predicting patient survival. Further verification is warranted, with prospective testing using large sample sizes. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  8. Identifying the origin of waterbird carcasses in Lake Michigan using a neural network source tracking model

    Science.gov (United States)

    Kenow, Kevin P.; Ge, Zhongfu; Fara, Luke J.; Houdek, Steven C.; Lubinski, Brian R.

    2016-01-01

    Avian botulism type E is responsible for extensive waterbird mortality on the Great Lakes, yet the actual site of toxin exposure remains unclear. Beached carcasses are often used to describe the spatial aspects of botulism mortality outbreaks, but lack specificity of offshore toxin source locations. We detail methodology for developing a neural network model used for predicting waterbird carcass motions in response to wind, wave, and current forcing, in lieu of a complex analytical relationship. This empirically trained model uses current velocity, wind velocity, significant wave height, and wave peak period in Lake Michigan simulated by the Great Lakes Coastal Forecasting System. A detailed procedure is further developed to use the model for back-tracing waterbird carcasses found on beaches in various parts of Lake Michigan, which was validated using drift data for radiomarked common loon (Gavia immer) carcasses deployed at a variety of locations in northern Lake Michigan during September and October of 2013. The back-tracing model was further used on 22 non-radiomarked common loon carcasses found along the shoreline of northern Lake Michigan in October and November of 2012. The model-estimated origins of those cases pointed to some common source locations offshore that coincide with concentrations of common loons observed during aerial surveys. The neural network source tracking model provides a promising approach for identifying locations of botulinum neurotoxin type E intoxication and, in turn, contributes to developing an understanding of the dynamics of toxin production and possible trophic transfer pathways.

  9. Identifying critical success factors (CSFs) of implementing building information modeling (BIM) in Malaysian construction industry

    Science.gov (United States)

    Yaakob, Mazri; Ali, Wan Nur Athirah Wan; Radzuan, Kamaruddin

    2016-08-01

    Building Information Modeling (BIM) is defined as existing from the earliest concept to demolition and it involves creating and using an intelligent 3D model to inform and communicate project decisions. This research aims to identify the critical success factors (CSFs) of BIM implementation in Malaysian construction industry. A literature review was done to explore previous BIM studies on definitions and history of BIM, construction issues, application of BIM in construction projects as well as benefits of BIM. A series of interviews with multidisciplinary Malaysian construction experts will be conducted purposely for data collection process guided by the research design and methodology approach of this study. The analysis of qualitative data from the process will be combined with criteria identified in the literature review in order to identify the CSFs. Finally, the CSFs of BIM implementation will be validated by further Malaysian industrialists during a workshop. The validated CSFs can be used as a term of reference for both Malaysian practitioners and academics towards measuring BIM effectiveness level in their organizations.

  10. Modeling strategy to identify patients with primary immunodeficiency utilizing risk management and outcome measurement.

    Science.gov (United States)

    Modell, Vicki; Quinn, Jessica; Ginsberg, Grant; Gladue, Ron; Orange, Jordan; Modell, Fred

    2017-06-01

    This study seeks to generate analytic insights into risk management and probability of an identifiable primary immunodeficiency defect. The Jeffrey Modell Centers Network database, Jeffrey Modell Foundation's 10 Warning Signs, the 4 Stages of Testing Algorithm, physician-reported clinical outcomes, programs of physician education and public awareness, the SPIRIT® Analyzer, and newborn screening, taken together, generates P values of less than 0.05%. This indicates that the data results do not occur by chance, and that there is a better than 95% probability that the data are valid. The objectives are to improve patients' quality of life, while generating significant reduction of costs. The advances of the world's experts aligned with these JMF programs can generate analytic insights as to risk management and probability of an identifiable primary immunodeficiency defect. This strategy reduces the uncertainties related to primary immunodeficiency risks, as we can screen, test, identify, and treat undiagnosed patients. We can also address regional differences and prevalence, age, gender, treatment modalities, and sites of care, as well as economic benefits. These tools support high net benefits, substantial financial savings, and significant reduction of costs. All stakeholders, including patients, clinicians, pharmaceutical companies, third party payers, and government healthcare agencies, must address the earliest possible precise diagnosis, appropriate intervention and treatment, as well as stringent control of healthcare costs through risk assessment and outcome measurement. An affected patient is entitled to nothing less, and stakeholders are responsible to utilize tools currently available. Implementation offers a significant challenge to the entire primary immunodeficiency community.

  11. Identifying damage locations under ambient vibrations utilizing vector autoregressive models and Mahalanobis distances

    Science.gov (United States)

    Mosavi, A. A.; Dickey, D.; Seracino, R.; Rizkalla, S.

    2012-01-01

    This paper presents a study for identifying damage locations in an idealized steel bridge girder using the ambient vibration measurements. A sensitive damage feature is proposed in the context of statistical pattern recognition to address the damage detection problem. The study utilizes an experimental program that consists of a two-span continuous steel beam subjected to ambient vibrations. The vibration responses of the beam are measured along its length under simulated ambient vibrations and different healthy/damage conditions of the beam. The ambient vibration is simulated using a hydraulic actuator, and damages are induced by cutting portions of the flange at two locations. Multivariate vector autoregressive models were fitted to the vibration response time histories measured at the multiple sensor locations. A sensitive damage feature is proposed for identifying the damage location by applying Mahalanobis distances to the coefficients of the vector autoregressive models. A linear discriminant criterion was used to evaluate the amount of variations in the damage features obtained for different sensor locations with respect to the healthy condition of the beam. The analyses indicate that the highest variations in the damage features were coincident with the sensors closely located to the damages. The presented method showed a promising sensitivity to identify the damage location even when the induced damage was very small.

  12. Illustrating Electric Conductivity Using the Particle-in-a-Box Model: Quantum Superposition is the Key

    CERN Document Server

    Sivanesan, Umaseh; Izmaylov, Artur F

    2016-01-01

    Most of the textbooks explaining electric conductivity in the context of quantum mechanics provide either incomplete or semi-classical explanations that are not connected with the elementary concepts of quantum mechanics. We illustrate the conduction phenomena using the simplest model system in quantum dynamics, a particle in a box (PIB). To induce the particle dynamics, a linear potential tilting the bottom of the box is introduced, which is equivalent to imposing a constant electric field for a charged particle. Although the PIB model represents a closed system that cannot have a flow of electrons through the system, we consider the oscillatory dynamics of the particle probability density as the analogue of the electric current. Relating the amplitude and other parameters of the particle oscillatory dynamics with the gap between the ground and excited states of the PIB model allows us to demonstrate one of the most basic dependencies of electric conductivity on the valence-conduction band gap of the materia...

  13. An Innovative Mathematical Model: A Key to the Riddle of HbA1c

    Directory of Open Access Journals (Sweden)

    Mahdi Kahrom

    2010-01-01

    Full Text Available HbA1c is a standard clinical assessment of glycemia and the basis of most data relating glycemic control to complications. While daily blood glucose testing gives a picture of day-to-day fluctuations, the HbA1c test offers an overview of how well glucose has been controlled over the past 4 months. I devised an innovative mathematical model to describe novel equations governing HbA1c which enables analysis of HbA1c behavior and provides emerging new concepts in assessment of diabetes management. Linear relationship of HbA1c and mean plasma glucose along with the kinetic analysis of HbA1c formation has been used as the basic suppositions to construct this model. The main application of this devised model is prediction of mean plasma glucose at any desired point in time after a change in therapy and with great certainty. This model also appraises the pattern of HbA1c changes over time and provides a unique opportunity to address common mistakes and misconceptions in routine application of HbA1c that could have potentially important implications on diabetes control.

  14. Key features of the IPSL ocean atmosphere model and its sensitivity to atmospheric resolution

    Energy Technology Data Exchange (ETDEWEB)

    Marti, Olivier; Braconnot, P.; Bellier, J.; Brockmann, P.; Caubel, A.; Noblet, N. de; Friedlingstein, P.; Idelkadi, A.; Kageyama, M. [Unite Mixte CEA-CNRS-UVSQ, IPSL/LSCE, Gif-sur-Yvette Cedex (France); Dufresne, J.L.; Bony, S.; Codron, F.; Fairhead, L.; Grandpeix, J.Y.; Hourdin, F.; Musat, I. [Unite Mixte CNRS-Ecole Polytechnique-ENS-UPCM, IPSL/LMD, Paris Cedex 05 (France); Benshila, R.; Guilyardi, E.; Levy, C.; Madec, G.; Mignot, J.; Talandier, C. [unite mixte CNRS-IRD-UPMC, IPLS/LOCEAN, Paris Cedex 05 (France); Cadule, P.; Denvil, S.; Foujols, M.A. [Institut Pierre Simon Laplace des Sciences de l' Environnement (IPSL), Paris Cedex 05 (France); Fichefet, T.; Goosse, H. [Universite Catholique de Louvain, Institut d' Astronomie et de Geophysique Georges Lemaitre, Louvain-la-Neuve (Belgium); Krinner, G. [Unite mixte CNRS-UJF Grenoble, LGGE, BP96, Saint-Martin-d' Heres (France); Swingedouw, D. [CNRS/CERFACS, Toulouse (France)

    2010-01-15

    This paper presents the major characteristics of the Institut Pierre Simon Laplace (IPSL) coupled ocean-atmosphere general circulation model. The model components and the coupling methodology are described, as well as the main characteristics of the climatology and interannual variability. The model results of the standard version used for IPCC climate projections, and for intercomparison projects like the Paleoclimate Modeling Intercomparison Project (PMIP 2) are compared to those with a higher resolution in the atmosphere. A focus on the North Atlantic and on the tropics is used to address the impact of the atmosphere resolution on processes and feedbacks. In the North Atlantic, the resolution change leads to an improved representation of the storm-tracks and the North Atlantic oscillation. The better representation of the wind structure increases the northward salt transports, the deep-water formation and the Atlantic meridional overturning circulation. In the tropics, the ocean-atmosphere dynamical coupling, or Bjerknes feedback, improves with the resolution. The amplitude of ENSO (El Nino-Southern oscillation) consequently increases, as the damping processes are left unchanged. (orig.)

  15. Using Stochastic modelling to identify unusual continuous glucose monitor measurements and behaviour, in newborn infants

    Directory of Open Access Journals (Sweden)

    Signal Matthew

    2012-08-01

    Full Text Available Abstract Background Abnormal blood glucose (BG concentrations have been associated with increased morbidity and mortality in both critically ill adults and infants. Furthermore, hypoglycaemia and glycaemic variability have both been independently linked to mortality in these patients. Continuous Glucose Monitoring (CGM devices have the potential to improve detection and diagnosis of these glycaemic abnormalities. However, sensor noise is a trade-off of the high measurement rate and must be managed effectively if CGMs are going to be used to monitor, diagnose and potentially help treat glycaemic abnormalities. Aim To develop a tool that will aid clinicians in identifying unusual CGM behaviour and highlight CGM data that potentially need to be interpreted with care. Methods CGM data and BG measurements from 50 infants at risk of hypoglycaemia were used. Unusual CGM measurements were classified using a stochastic model based on the kernel density method and historical CGM measurements from the cohort. CGM traces were colour coded with very unusual measurements coloured red, highlighting areas to be interpreted with care. A 5-fold validation of the model was Monte Carlo simulated 25 times to ensure an adequate model fit. Results The stochastic model was generated using ~67,000 CGM measurements, spread across the glycaemic range ~2-10 mmol/L. A 5-fold validation showed a good model fit: the model 80% confidence interval (CI captured 83% of clinical CGM data, the model 90% CI captured 91% of clinical CGM data, and the model 99% CI captured 99% of clinical CGM data. Three patient examples show the stochastic classification method in use with 1 A stable, low variability patient which shows no unusual CGM measurements, 2 A patient with a very sudden, short hypoglycaemic event (classified as unusual, and, 3 A patient with very high, potentially un-physiological, glycaemic variability after day 3 of monitoring (classified as very unusual. Conclusions

  16. Multiplicity fluctuation and correlation of identified baryons in quark combination model

    CERN Document Server

    Song, Jun; Wang, Rui-qin; Shao, Feng-lan

    2016-01-01

    The dynamical fluctuation and correlation of multiplicity distributions of identified baryons and antibaryons produced by the hadronization of the bulk quark system are systematically studied in quark combination model. Starting from the most basic dynamics of quark combination which are necessary for multiplicity study, we analyze moments (variance, skewness and kurtosis) of inclusive multiplicity distribution of identified baryons, two-baryon multiplicity correlations, and baryon-antibaryon multiplicity correlations after the hadronization of quark system with given quark number and antiquark number. We obtain a series of interesting findings, e.g., binomial behavior of multiplicity moments, coincide flavor dependent two-baryon correlation and universal baryon-antibaryon correlation, which can be regarded as general features of quark combination. We further take into account correlations and fluctuations of quark numbers before hadronization to study their influence on multiple production of baryons and ant...

  17. The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

    Science.gov (United States)

    Van Kampen, Jackalina M; Baranowski, David C; Robertson, Harold A; Shaw, Christopher A; Kay, Denis G

    2015-01-01

    The development of effective neuroprotective therapies for Parkinson's disease (PD) has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG) triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the olfactory bulb, then

  18. Three-stage Method for Identifying the Dynamic Model Parameters of Stranded Wire Helical Springs

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu; WANG Shilong; ZHOU Jie; LI Chuan; SUN Shouli

    2015-01-01

    The dynamic behavior of the stranded wire helical spring is described by a modified Bouc-Wen model while the model parameters must be identified using an identification method and experimental data. Existing identification methods usually relies either solely nonlinear iterative algorithms or manually trial and error. Therefore, the identification process can be rather time consuming and effort taking. As a result, these methods are not ideal for engineering applications. To come up with a more practical method, a three-stage identification method is proposed. Periodic loading and identification simulations are carried out to verify the effectiveness of the proposed method. Noises are added to the simulated data to test the performance of the proposed method when dealing with noise contaminated data. The simulation results indicate that the proposed method is able to give satisfying results when the noise levels are set to be 0.01, 0.03, 0.05 and 0.07. In addition, the proposed method is also applied to experimental data and compared with an existing method. The experimental data is acquired through a periodic loading test. The experiment results suggest that the proposed method features better accuracy compared with the existing method. An effective approach is proposed for identifying the model parameters of the stranded wire helical spring.

  19. Models of self-peptide sampling by developing T cells identify candidate mechanisms of thymic selection.

    Directory of Open Access Journals (Sweden)

    Iren Bains

    Full Text Available Conventional and regulatory T cells develop in the thymus where they are exposed to samples of self-peptide MHC (pMHC ligands. This probabilistic process selects for cells within a range of responsiveness that allows the detection of foreign antigen without excessive responses to self. Regulatory T cells are thought to lie at the higher end of the spectrum of acceptable self-reactivity and play a crucial role in the control of autoimmunity and tolerance to innocuous antigens. While many studies have elucidated key elements influencing lineage commitment, we still lack a full understanding of how thymocytes integrate signals obtained by sampling self-peptides to make fate decisions. To address this problem, we apply stochastic models of signal integration by T cells to data from a study quantifying the development of the two lineages using controllable levels of agonist peptide in the thymus. We find two models are able to explain the observations; one in which T cells continually re-assess fate decisions on the basis of multiple summed proximal signals from TCR-pMHC interactions; and another in which TCR sensitivity is modulated over time, such that contact with the same pMHC ligand may lead to divergent outcomes at different stages of development. Neither model requires that T(conv and T(reg are differentially susceptible to deletion or that the two lineages need qualitatively different signals for development, as have been proposed. We find additional support for the variable-sensitivity model, which is able to explain apparently paradoxical observations regarding the effect of partial and strong agonists on T(conv and T(reg development.

  20. Identifying areas of deforestation risk for REDD+ using a species modeling tool.

    Science.gov (United States)

    Aguilar-Amuchastegui, Naikoa; Riveros, Juan Carlos; Forrest, Jessica L

    2014-01-01

    To implement the REDD+ mechanism (Reducing Emissions for Deforestation and Forest Degradation, countries need to prioritize areas to combat future deforestation CO2 emissions, identify the drivers of deforestation around which to develop mitigation actions, and quantify and value carbon for financial mechanisms. Each comes with its own methodological challenges, and existing approaches and tools to do so can be costly to implement or require considerable technical knowledge and skill. Here, we present an approach utilizing a machine learning technique known as Maximum Entropy Modeling (Maxent) to identify areas at high deforestation risk in the study area in Madre de Dios, Peru under a business-as-usual scenario in which historic deforestation rates continue. We link deforestation risk area to carbon density values to estimate future carbon emissions. We quantified area deforested and carbon emissions between 2000 and 2009 as the basis of the scenario. We observed over 80,000 ha of forest cover lost from 2000-2009 (0.21% annual loss), representing over 39 million Mg CO2. The rate increased rapidly following the enhancement of the Inter Oceanic Highway in 2005. Accessibility and distance to previous deforestation were strong predictors of deforestation risk, while land use designation was less important. The model performed consistently well (AUC > 0.9), significantly better than random when we compared predicted deforestation risk to observed. If past deforestation rates continue, we estimate that 132,865 ha of forest could be lost by the year 2020, representing over 55 million Mg CO2. Maxent provided a reliable method for identifying areas at high risk of deforestation and the major explanatory variables that could draw attention for mitigation action planning under REDD+. The tool is accessible, replicable and easy to use; all necessary for producing good risk estimates and adapt models after potential landscape change. We propose this approach for developing

  1. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  2. Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

    DEFF Research Database (Denmark)

    Huang, Sijia; Chong, Nicole; Lewis, Nathan

    2016-01-01

    . Methods: We propose that higher-order functional representation of metabolomics data, such as pathway-based metabolomic features, can be used as robust biomarkers for breast cancer. Towards this, we have developed a new computational method that uses personalized pathway dysregulation scores for disease...... the Curve, a receiver operating characteristic curve) of 0.968 and 0.934, sensitivities of 0.946 and 0.954, and specificities of 0.934 and 0.918. These two metabolomics-based pathway models are further validated by RNA-Seq-based TCGA (The Cancer Genome Atlas) breast cancer data, with AUCs of 0.995 and 0.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...

  3. Selection in spatial stochastic models of cancer: Migration as a key modulator of fitness

    Directory of Open Access Journals (Sweden)

    Stupack Dwayne

    2010-04-01

    Full Text Available Abstract Background We study the selection dynamics in a heterogeneous spatial colony of cells. We use two spatial generalizations of the Moran process, which include cell divisions, death and migration. In the first model, migration is included explicitly as movement to a proximal location. In the second, migration is implicit, through the varied ability of cell types to place their offspring a distance away, in response to another cell's death. Results In both models, we find that migration has a direct positive impact on the ability of a single mutant cell to invade a pre-existing colony. Thus, a decrease in the growth potential can be compensated by an increase in cell migration. We further find that the neutral ridges (the set of all types with the invasion probability equal to that of the host cells remain invariant under the increase of system size (for large system sizes, thus making the invasion probability a universal characteristic of the cells selection status. We find that repeated instances of large scale cell-death, such as might arise during therapeutic intervention or host response, strongly select for the migratory phenotype. Conclusions These models can help explain the many examples in the biological literature, where genes involved in cell's migratory and invasive machinery are also associated with increased cellular fitness, even though there is no known direct effect of these genes on the cellular reproduction. The models can also help to explain how chemotherapy may provide a selection mechanism for highly invasive phenotypes. Reviewers This article was reviewed by Marek Kimmel and Glenn Webb.

  4. Scenario-Led Habitat Modelling of Land Use Change Impacts on Key Species.

    Directory of Open Access Journals (Sweden)

    Matthew Geary

    Full Text Available Accurate predictions of the impacts of future land use change on species of conservation concern can help to inform policy-makers and improve conservation measures. If predictions are spatially explicit, predicted consequences of likely land use changes could be accessible to land managers at a scale relevant to their working landscape. We introduce a method, based on open source software, which integrates habitat suitability modelling with scenario-building, and illustrate its use by investigating the effects of alternative land use change scenarios on landscape suitability for black grouse Tetrao tetrix. Expert opinion was used to construct five near-future (twenty years scenarios for the 800 km2 study site in upland Scotland. For each scenario, the cover of different land use types was altered by 5-30% from 20 random starting locations and changes in habitat suitability assessed by projecting a MaxEnt suitability model onto each simulated landscape. A scenario converting grazed land to moorland and open forestry was the most beneficial for black grouse, and 'increased grazing' (the opposite conversion the most detrimental. Positioning of new landscape blocks was shown to be important in some situations. Increasing the area of open-canopy forestry caused a proportional decrease in suitability, but suitability gains for the 'reduced grazing' scenario were nonlinear. 'Scenario-led' landscape simulation models can be applied in assessments of the impacts of land use change both on individual species and also on diversity and community measures, or ecosystem services. A next step would be to include landscape configuration more explicitly in the simulation models, both to make them more realistic, and to examine the effects of habitat placement more thoroughly. In this example, the recommended policy would be incentives on grazing reduction to benefit black grouse.

  5. Scenario-Led Habitat Modelling of Land Use Change Impacts on Key Species.

    Science.gov (United States)

    Geary, Matthew; Fielding, Alan H; McGowan, Philip J K; Marsden, Stuart J

    2015-01-01

    Accurate predictions of the impacts of future land use change on species of conservation concern can help to inform policy-makers and improve conservation measures. If predictions are spatially explicit, predicted consequences of likely land use changes could be accessible to land managers at a scale relevant to their working landscape. We introduce a method, based on open source software, which integrates habitat suitability modelling with scenario-building, and illustrate its use by investigating the effects of alternative land use change scenarios on landscape suitability for black grouse Tetrao tetrix. Expert opinion was used to construct five near-future (twenty years) scenarios for the 800 km2 study site in upland Scotland. For each scenario, the cover of different land use types was altered by 5-30% from 20 random starting locations and changes in habitat suitability assessed by projecting a MaxEnt suitability model onto each simulated landscape. A scenario converting grazed land to moorland and open forestry was the most beneficial for black grouse, and 'increased grazing' (the opposite conversion) the most detrimental. Positioning of new landscape blocks was shown to be important in some situations. Increasing the area of open-canopy forestry caused a proportional decrease in suitability, but suitability gains for the 'reduced grazing' scenario were nonlinear. 'Scenario-led' landscape simulation models can be applied in assessments of the impacts of land use change both on individual species and also on diversity and community measures, or ecosystem services. A next step would be to include landscape configuration more explicitly in the simulation models, both to make them more realistic, and to examine the effects of habitat placement more thoroughly. In this example, the recommended policy would be incentives on grazing reduction to benefit black grouse.

  6. Epidemiological Implications of Host Biodiversity and Vector Biology: Key Insights from Simple Models.

    Science.gov (United States)

    Dobson, Andrew D M; Auld, Stuart K J R

    2016-04-01

    Models used to investigate the relationship between biodiversity change and vector-borne disease risk often do not explicitly include the vector; they instead rely on a frequency-dependent transmission function to represent vector dynamics. However, differences between classes of vector (e.g., ticks and insects) can cause discrepancies in epidemiological responses to environmental change. Using a pair of disease models (mosquito- and tick-borne), we simulated substitutive and additive biodiversity change (where noncompetent hosts replaced or were added to competent hosts, respectively), while considering different relationships between vector and host densities. We found important differences between classes of vector, including an increased likelihood of amplified disease risk under additive biodiversity change in mosquito models, driven by higher vector biting rates. We also draw attention to more general phenomena, such as a negative relationship between initial infection prevalence in vectors and likelihood of dilution, and the potential for a rise in density of infected vectors to occur simultaneously with a decline in proportion of infected hosts. This has important implications; the density of infected vectors is the most valid metric for primarily zoonotic infections, while the proportion of infected hosts is more relevant for infections where humans are a primary host.

  7. The meta-volition model: organizational leadership is the key ingredient in getting society moving, literally!

    Science.gov (United States)

    Yancey, Antronette K

    2009-10-01

    This paper argues that substantive and sustainable population-wide improvements in physical activity can be achieved only through the large scale adoption and implementation of policies and practices that make being active the default choice and remaining inactive difficult. Meta-volition refers to the volition and collective agency of early adopter leaders who implement such changes in their own organizations to drive productivity and health improvements. Leaders, themselves, are motivated by strong incentives to accomplish their organizational missions. The meta-volition model (MVM) specifies a cascade of changes that may be sparked by structural integration of brief activity bouts into organizational routine across sectors and types of organizations. MVM builds upon inter-disciplinary social ecological change models and frameworks such as diffusion of innovations, social learning and social marketing. MVM is dynamic rather than static, integrating biological influences with psychological factors, and socio-cultural influences with organizational processes. The model proposes six levels of dissemination triggered by organizational marketing to early adopter leaders carried out by "sparkplugs," boisterous leaders in population physical activity promotion: initiating (leader-leader), catalyzing (organizational-individual), viral marketing (individual-organizational), accelerating (organizational-organizational), anchoring (organizational-community) and institutionalizing (community-individual). MVM embodies public-private partnership principles, a collective investment in the high cost of achieving and maintaining active lifestyles.

  8. Nuclear inputs of key iron isotopes for core-collapse modeling and simulation

    CERN Document Server

    Nabi, Jameel-Un

    2014-01-01

    From the modeling and simulation results of presupernova evolution of massive stars, it was found that isotopes of iron, $^{54,55,56}$Fe, play a significant role inside the stellar cores, primarily decreasing the electron-to-baryon ratio ($Y_{e}$) mainly via electron capture processes thereby reducing the pressure support. The neutrinos produced, as a result of these capture processes, are transparent to the stellar matter and assist in cooling the core thereby reducing the entropy. The structure of the presupernova star is altered both by the changes in $Y_{e}$ and the entropy of the core material. Here we present the microscopic calculation of Gamow-Teller strength distributions for isotopes of iron. The calculation is also compared with other theoretical models and experimental data. Presented also are stellar electron capture rates and associated neutrino cooling rates, due to isotopes of iron, in a form suitable for simulation and modeling codes. It is hoped that the nuclear inputs presented here should ...

  9. Identifiability and Problems of Model Selection for Time-Series Analysis in Econometrics.

    Science.gov (United States)

    1980-01-01

    feedback", in Proc. 1971 NRL-.IS Con- ference on Ordinary Differential Equations , edited by L. Weiss, Acalumic Press, pazes 459-471. REKA Dr Pai-,e...abstract sense. The difficulty is nonuniqueness , not identifiability. Third, there is the question of parametrization of models. In econo- metrics...with the equation (a) + -1, O, i, where u i t is a linear stochastic process whose values ( h ) " f K c t _ Tr=O ’t - are generated with the aid of

  10. Proteomic profiling identifies breast tumor metastasis-associated factors in an isogenic model

    OpenAIRE

    KREUNIN, PAWEENA; YOO, CHUL; Urquidi, Virginia; Lubman, David M.; Goodison, Steve

    2007-01-01

    A combination of LC and MS was applied to an isogenic breast tumor metastasis model to identify proteins associated with a cellular phenotype. Chromatofocusing followed by nonporous-RP-HPLC/ESI-TOF MS was applied to cell lysates of a pair of monoclonal cell lines from the human breast carcinoma cell line MDA-MB-435 that have different metastatic phenotypes in immune-compromised mice. This method was developed to separate proteins based on pI and hydrophobicity. The high resolution and mass ac...

  11. Application of the transtheoretical model to identify aspects influencing condom use among Korean college students.

    Science.gov (United States)

    Kwon, Young Mi; Yeun, Eun Ja; Kim, Hee Young; Youn, Mi Sun; Cho, Ju Yeon; Lee, Hee Joo

    2008-12-01

    Increasing condom use requires an understanding of the influencing factors. Previous research has used psychosocial theories such as the social cognitive theory and health belief to explain AIDS risk factors and condom use. However, it is still difficult to effectively predict the multidimensional factors associated with condom use. The present study utilizes the transtheoretical model to investigate condom use among college students by examining stages of change for condom use and measuring decisional balance and self-efficacy for each stage. The aim was to identify the variables affecting condom use so as to provide scientific data that would aid the development of effective strategies for increasing condom use.

  12. The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

    Directory of Open Access Journals (Sweden)

    Jackalina M Van Kampen

    Full Text Available The development of effective neuroprotective therapies for Parkinson's disease (PD has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the

  13. Concept design theory and model for multi-use space facilities: Analysis of key system design parameters through variance of mission requirements

    Science.gov (United States)

    Reynerson, Charles Martin

    This research has been performed to create concept design and economic feasibility data for space business parks. A space business park is a commercially run multi-use space station facility designed for use by a wide variety of customers. Both space hardware and crew are considered as revenue producing payloads. Examples of commercial markets may include biological and materials research, processing, and production, space tourism habitats, and satellite maintenance and resupply depots. This research develops a design methodology and an analytical tool to create feasible preliminary design information for space business parks. The design tool is validated against a number of real facility designs. Appropriate model variables are adjusted to ensure that statistical approximations are valid for subsequent analyses. The tool is used to analyze the effect of various payload requirements on the size, weight and power of the facility. The approach for the analytical tool was to input potential payloads as simple requirements, such as volume, weight, power, crew size, and endurance. In creating the theory, basic principles are used and combined with parametric estimation of data when necessary. Key system parameters are identified for overall system design. Typical ranges for these key parameters are identified based on real human spaceflight systems. To connect the economics to design, a life-cycle cost model is created based upon facility mass. This rough cost model estimates potential return on investments, initial investment requirements and number of years to return on the initial investment. Example cases are analyzed for both performance and cost driven requirements for space hotels, microgravity processing facilities, and multi-use facilities. In combining both engineering and economic models, a design-to-cost methodology is created for more accurately estimating the commercial viability for multiple space business park markets.

  14. Probing the dynamics of identified neurons with a data-driven modeling approach.

    Directory of Open Access Journals (Sweden)

    Thomas Nowotny

    Full Text Available In controlling animal behavior the nervous system has to perform within the operational limits set by the requirements of each specific behavior. The implications for the corresponding range of suitable network, single neuron, and ion channel properties have remained elusive. In this article we approach the question of how well-constrained properties of neuronal systems may be on the neuronal level. We used large data sets of the activity of isolated invertebrate identified cells and built an accurate conductance-based model for this cell type using customized automated parameter estimation techniques. By direct inspection of the data we found that the variability of the neurons is larger when they are isolated from the circuit than when in the intact system. Furthermore, the responses of the neurons to perturbations appear to be more consistent than their autonomous behavior under stationary conditions. In the developed model, the constraints on different parameters that enforce appropriate model dynamics vary widely from some very tightly controlled parameters to others that are almost arbitrary. The model also allows predictions for the effect of blocking selected ionic currents and to prove that the origin of irregular dynamics in the neuron model is proper chaoticity and that this chaoticity is typical in an appropriate sense. Our results indicate that data driven models are useful tools for the in-depth analysis of neuronal dynamics. The better consistency of responses to perturbations, in the real neurons as well as in the model, suggests a paradigm shift away from measuring autonomous dynamics alone towards protocols of controlled perturbations. Our predictions for the impact of channel blockers on the neuronal dynamics and the proof of chaoticity underscore the wide scope of our approach.

  15. Integrative strategies to identify candidate genes in rodent models of human alcoholism.

    Science.gov (United States)

    Treadwell, Julie A

    2006-01-01

    The search for genes underlying alcohol-related behaviours in rodent models of human alcoholism has been ongoing for many years with only limited success. Recently, new strategies that integrate several of the traditional approaches have provided new insights into the molecular mechanisms underlying ethanol's actions in the brain. We have used alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) genetic strains of mice in an integrative strategy combining high-throughput gene expression screening, genetic segregation analysis, and mapping to previously published quantitative trait loci to uncover candidate genes for the ethanol-preference phenotype. In our study, 2 genes, retinaldehyde binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), were found to be strong candidates for ethanol preference. Such experimental approaches have the power and the potential to greatly speed up the laborious process of identifying candidate genes for the animal models of human alcoholism.

  16. Boolean modeling identifies Greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma.

    Science.gov (United States)

    Dahlhaus, Meike; Burkovski, Andre; Hertwig, Falk; Mussel, Christoph; Volland, Ruth; Fischer, Matthias; Debatin, Klaus-Michael; Kestler, Hans A; Beltinger, Christian

    2016-02-01

    Aurora Kinase A (AURKA) is often overexpressed in neuroblastoma (NB) with poor outcome. The causes of AURKA overexpression in NB are unknown. Here, we describe a gene regulatory network consisting of core regulators of AURKA protein expression and activation during mitosis to identify potential causes. This network was transformed to a dynamic Boolean model. Simulated activation of the serine/threonine protein kinase Greatwall (GWL, encoded by MASTL) that attenuates the pivotal AURKA inhibitor PP2A, predicted stabilization of AURKA. Consistent with this notion, gene set enrichment analysis showed enrichment of mitotic spindle assembly genes and MYCN target genes in NB with high GWL/MASTL expression. In line with the prediction of GWL/MASTL enhancing AURKA, elevated expression of GWL/MASTL was associated with NB risk factors and poor survival of patients. These results establish Boolean network modeling of oncogenic pathways in NB as a useful means for guided discovery in this enigmatic cancer.

  17. A model to identify urban traffic congestion hotspots in complex networks

    CERN Document Server

    Solé-Ribalta, Albert; Arenas, Alex

    2016-01-01

    The rapid growth of population in urban areas is jeopardizing the mobility and air quality worldwide. One of the most notable problems arising is that of traffic congestion. With the advent of technologies able to sense real-time data about cities, and its public distribution for analysis, we are in place to forecast scenarios valuable for improvement and control. Here, we propose an idealized model, based on the critical phenomena arising in complex networks, that allows to analytically predict congestion hotspots in urban environments. Results on real cities' road networks, considering, in some experiments, real-traffic data, show that the proposed model is capable of identifying susceptible junctions that might becomes hotspots if mobility demand increases.

  18. Identifying common components across biological network graphs using a bipartite data model.

    Science.gov (United States)

    Baker, Ej; Culpepper, C; Philips, C; Bubier, J; Langston, M; Chesler, Ej

    2014-01-01

    The GeneWeaver bipartite data model provides an efficient means to evaluate shared molecular components from sets derived across diverse species, disease states and biological processes. In order to adapt this model for examining related molecular components and biological networks, such as pathway or gene network data, we have developed a means to leverage the bipartite data structure to extract and analyze shared edges. Using the Pathway Commons database we demonstrate the ability to rapidly identify shared connected components among a diverse set of pathways. In addition, we illustrate how results from maximal bipartite discovery can be decomposed into hierarchical relationships, allowing shared pathway components to be mapped through various parent-child relationships to help visualization and discovery of emergent kernel driven relationships. Interrogating common relationships among biological networks and conventional GeneWeaver gene lists will increase functional specificity and reliability of the shared biological components. This approach enables self-organization of biological processes through shared biological networks.

  19. A model to identify urban traffic congestion hotspots in complex networks

    Science.gov (United States)

    Solé-Ribalta, Albert; Gómez, Sergio; Arenas, Alex

    2016-10-01

    The rapid growth of population in urban areas is jeopardizing the mobility and air quality worldwide. One of the most notable problems arising is that of traffic congestion. With the advent of technologies able to sense real-time data about cities, and its public distribution for analysis, we are in place to forecast scenarios valuable for improvement and control. Here, we propose an idealized model, based on the critical phenomena arising in complex networks, that allows to analytically predict congestion hotspots in urban environments. Results on real cities' road networks, considering, in some experiments, real traffic data, show that the proposed model is capable of identifying susceptible junctions that might become hotspots if mobility demand increases.

  20. A Simple Model to Identify Risk of Sarcopenia and Physical Disability in HIV-Infected Patients.

    Science.gov (United States)

    Farinatti, Paulo; Paes, Lorena; Harris, Elizabeth A; Lopes, Gabriella O; Borges, Juliana P

    2017-09-01

    Farinatti, P, Paes, L, Harris, EA, Lopes, GO, and Borges, JP. A simple model to identify risk of sarcopenia and physical disability in HIV-infected patients. J Strength Cond Res 31(9): 2542-2551, 2017-Early detection of sarcopenia might help preventing muscle loss and disability in HIV-infected patients. This study proposed a model for estimating appendicular skeletal muscle mass (ASM) to calculate indices to identify "sarcopenia" (SA) and "risk for disability due to sarcopenia" (RSA) in patients with HIV. An equation to estimate ASM was developed in 56 patients (47.2 ± 6.9 years), with a cross-validation sample of 24 patients (48.1 ± 6.6 years). The model validity was determined by calculating, in both samples: (a) Concordance between actual vs. estimated ASM; (b) Correlations between actual/estimated ASM vs. peak torque (PT) and total work (TW) during isokinetic knee extension/flexion; (c) Agreement of patients classified with SA and RSA. The predictive equation was ASM (kg) = 7.77 (sex; F = 0/M = 1) + 0.26 (arm circumference; cm) + 0.38 (thigh circumference; cm) + 0.03 (Body Mass Index; kg·m) - 8.94 (R = 0.74; Radj = 0.72; SEE = 3.13 kg). Agreement between actual vs. estimated ASM was confirmed in validation (t = 0.081/p = 0.94; R = 0.86/p < 0.0001) and cross-validation (t = 0.12/p = 0.92; R = 0.87/p < 0.0001) samples. Regression characteristics in cross-validation sample (Radj = 0.80; SEE = 3.65) and PRESS (RPRESS = 0.69; SEEPRESS = 3.35) were compatible with the original model. Percent agreements for the classification of SA and RSA from indices calculated using actual and estimated ASM were of 87.5% and 77.2% (gamma correlations 0.72-1.0; p < 0.04) in validation, and 95.8% and 75.0% (gamma correlations 0.98-0.97; p < 0.001) in cross-validation sample, respectively. Correlations between actual/estimated ASM vs. PT (range 0.50-0.73, p ≤ 0.05) and TW (range 0.59-0.74, p ≤ 0.05) were similar in both samples. In conclusion, our model correctly estimated ASM

  1. A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Simeone Marino

    2016-10-01

    Full Text Available Tuberculosis (TB is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB. The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs, take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung to lung-draining lymph nodes (LNs where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim describing in silico immune cell, bacterial (Mtb and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form, lung draining lymph node (LN, site of generation of adaptive immunity and blood (a measurable compartment. Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM, while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs. In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs in a computational fashion into GranSim. Results: The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. Conclusion: The main conclusion of this study is

  2. DESCARTES' RULE OF SIGNS AND THE IDENTIFIABILITY OF POPULATION DEMOGRAPHIC MODELS FROM GENOMIC VARIATION DATA.

    Science.gov (United States)

    Bhaskar, Anand; Song, Yun S

    2014-01-01

    The sample frequency spectrum (SFS) is a widely-used summary statistic of genomic variation in a sample of homologous DNA sequences. It provides a highly efficient dimensional reduction of large-scale population genomic data and its mathematical dependence on the underlying population demography is well understood, thus enabling the development of efficient inference algorithms. However, it has been recently shown that very different population demographies can actually generate the same SFS for arbitrarily large sample sizes. Although in principle this nonidentifiability issue poses a thorny challenge to statistical inference, the population size functions involved in the counterexamples are arguably not so biologically realistic. Here, we revisit this problem and examine the identifiability of demographic models under the restriction that the population sizes are piecewise-defined where each piece belongs to some family of biologically-motivated functions. Under this assumption, we prove that the expected SFS of a sample uniquely determines the underlying demographic model, provided that the sample is sufficiently large. We obtain a general bound on the sample size sufficient for identifiability; the bound depends on the number of pieces in the demographic model and also on the type of population size function in each piece. In the cases of piecewise-constant, piecewise-exponential and piecewise-generalized-exponential models, which are often assumed in population genomic inferences, we provide explicit formulas for the bounds as simple functions of the number of pieces. Lastly, we obtain analogous results for the "folded" SFS, which is often used when there is ambiguity as to which allelic type is ancestral. Our results are proved using a generalization of Descartes' rule of signs for polynomials to the Laplace transform of piecewise continuous functions.

  3. Identifying Training Images from Fracture Outcrops for MPS-based Modeling

    Science.gov (United States)

    Roy, A.; Mukerji, T.; Caers, J.

    2014-12-01

    Various MPS (multi-point geostatistics) based techniques have been successfully employed for modeling heterogeneous geologic features such as channel bodies. However, few studies exist on modeling fracture networks implementing MPS. Selecting a TI (training image) that is representative of the target subsurface fracture pattern is key to an effective implementation of any MPS algorithm. While recent research has employed equivalent continuum models created from Discrete Fracture Networks (DFN) to serve as TIs, the present research explores the direct usage of outcrop analogues of fracture networks for this purpose. A set of nested-fracture maps from the Devonian Sandstone of Hornelen basin created at multiple scales and resolutions is considered. These maps have been previously classified as belonging to a single fractal system characterized by a fractal dimension but having slightly different spatial organization at each scale. Our research implements unconditional image quilting in generating multiple realizations of fracture networks from these maps. This pattern-based algorithm requires a template-size to be chosen which is representative of the heterogeneity of the pattern of interest. Lacunarity is a technique that essentially quantifies the distribution of spaces or gaps in a pattern and can thus delineate scale-dependent heterogeneity. It is therefore investigated if this technique, in conjunction with Entropy (a measure for randomness), can be applied for choosing the template-size required for reproducing a desired pattern from a given TI. Finally, it will be tested if fracture networks generated from two or more TIs at different scales but belonging to the same fractal-fracture system, can capture similar ranges of uncertainty.

  4. The Laser Scan Data as a Key Element in the Hydraulic Flood Modelling in Urban Areas

    Science.gov (United States)

    Sole, A.; Giosa, L.; Albano, R.; Cantisani, A.

    2013-05-01

    This paper is intended to highlight the need to use data at high spatial resolution, such as those obtained through the use of Airborne Laser Scanning (ALS) techniques, to support hydraulic models for the assessment of flood hazards in urban territory. In fact, the significant structural features (houses, walls, roads, etc.) in the city are important in relation to both the volume of the floodplain that can be occupied by the flow and the direction that the flow takes across the floodplain. ALS data can range up to several terabytes in size and is a function of the geographic scale of the mission. Also, this data is typically irregular with uneven point density. Therefore, a quick method is described to ride out the difficulties to handle the large datasets with uneven point densities and to improve the extracting of feature information for further use in Geographic Information System (GIS) analysis. Finally, a comparison is made between the maximum inundated area obtained from ALS data and that one calculated using a traditional topographic map. The results show that the high-resolution data obtained from airborne remote sensing can increase the opportunities for representation of small-scale structural elements in complex systems using two-dimensional models of flood inundation.

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

    Science.gov (United States)

    Westoby, M.

    2014-12-01

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

  6. Assessing the performance of community-available global MHD models using key system parameters and empirical relationships

    Science.gov (United States)

    Gordeev, E.; Sergeev, V.; Honkonen, I.; Kuznetsova, M.; Rastätter, L.; Palmroth, M.; Janhunen, P.; Tóth, G.; Lyon, J.; Wiltberger, M.

    2015-12-01

    Global magnetohydrodynamic (MHD) modeling is a powerful tool in space weather research and predictions. There are several advanced and still developing global MHD (GMHD) models that are publicly available via Community Coordinated Modeling Center's (CCMC) Run on Request system, which allows the users to simulate the magnetospheric response to different solar wind conditions including extraordinary events, like geomagnetic storms. Systematic validation of GMHD models against observations still continues to be a challenge, as well as comparative benchmarking of different models against each other. In this paper we describe and test a new approach in which (i) a set of critical large-scale system parameters is explored/tested, which are produced by (ii) specially designed set of computer runs to simulate realistic statistical distributions of critical solar wind parameters and are compared to (iii) observation-based empirical relationships for these parameters. Being tested in approximately similar conditions (similar inputs, comparable grid resolution, etc.), the four models publicly available at the CCMC predict rather well the absolute values and variations of those key parameters (magnetospheric size, magnetic field, and pressure) which are directly related to the large-scale magnetospheric equilibrium in the outer magnetosphere, for which the MHD is supposed to be a valid approach. At the same time, the models have systematic differences in other parameters, being especially different in predicting the global convection rate, total field-aligned current, and magnetic flux loading into the magnetotail after the north-south interplanetary magnetic field turning. According to validation results, none of the models emerges as an absolute leader. The new approach suggested for the evaluation of the models performance against reality may be used by model users while planning their investigations, as well as by model developers and those interesting to quantitatively

  7. Development of personnel motivation models as a key component of innovative activity management

    Directory of Open Access Journals (Sweden)

    D.O. Krykunenko

    2014-03-01

    Full Text Available The aim of the article. The aim of the article is to examine the algorithm, approaches and methods of development the model of staff motivation at high technology enterprises, to strengthen the creative-directed processes of developing new products, as well as analysis of additional factors that have contributed to the effective creative work of the staff. The results of the analysis. The problem of improving the efficiency of different economic systems in the situation of limited amount of resources and fierce competition among enterprises is highlighted in the article. The author found that the performance of the considered task can be achieved through the active use of creative abilities of employees. Entities of innovative business must address the development of management concepts creativity of staff motivation model of creative work, the development and application of a wide range of methods and instruments for the control creativity. In this case, the algorithm of motivation improvement involves defining the objective model of motivation, diagnosis of the existing system of staff incentives, building a creative ranking of employees, development of effective methods of creative work motivation. Scientific novelty of the present study is in organizing of staff creativity management, which involves the intensification and revitalization innovations of the company, the aim of which is in development and implementation of innovative products. An important phase of model motivation is to create additional motivators manifestation of the creative energy of employees, which will increase the cost-effectiveness of high-tech enterprises, to reduce the turnaround time for the development of innovative products. Thus, the development, implementation and operation of the motivation model to incorporate the creative abilities of the staff of the enterprise should be based on an integrated, generalized, systemic and integrated approach, taking into

  8. A model-based approach to identify binding sites in CLIP-Seq data.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html, and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip for customized analysis.

  9. Identifying influential nodes in dynamic social networks based on degree-corrected stochastic block model

    Science.gov (United States)

    Wang, Tingting; Dai, Weidi; Jiao, Pengfei; Wang, Wenjun

    2016-05-01

    Many real-world data can be represented as dynamic networks which are the evolutionary networks with timestamps. Analy