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Sample records for approach identifies coordinated

  1. Using the Onto-Semiotic Approach to Identify and Analyze Mathematical Meaning when Transiting between Different Coordinate Systems in a Multivariate Context

    Science.gov (United States)

    Montiel, Mariana; Wilhelmi, Miguel R.; Vidakovic, Draga; Elstak, Iwan

    2009-01-01

    The main objective of this paper is to apply the onto-semiotic approach to analyze the mathematical concept of different coordinate systems, as well as some situations and university students' actions related to these coordinate systems. The identification of objects that emerge from the mathematical activity and a first intent to describe an…

  2. 'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus

    Directory of Open Access Journals (Sweden)

    Stürzenbaum Stephen R

    2008-06-01

    Full Text Available Abstract Background New methods are needed for research into non-model organisms, to monitor the effects of toxic disruption at both the molecular and functional organism level. We exposed earthworms (Lumbricus rubellus Hoffmeister to sub-lethal levels of copper (10–480 mg/kg soil for 70 days as a real-world situation, and monitored both molecular (cDNA transcript microarrays and nuclear magnetic resonance-based metabolic profiling: metabolomics and ecological/functional endpoints (reproduction rate and weight change, which have direct relevance to population-level impacts. Results Both of the molecular endpoints, metabolomics and transcriptomics, were highly sensitive, with clear copper-induced differences even at levels below those that caused a reduction in reproductive parameters. The microarray and metabolomic data provided evidence that the copper exposure led to a disruption of energy metabolism: transcripts of enzymes from oxidative phosphorylation were significantly over-represented, and increases in transcripts of carbohydrate metabolising enzymes (maltase-glucoamylase, mannosidase had corresponding decreases in small-molecule metabolites (glucose, mannose. Treating both enzymes and metabolites as functional cohorts led to clear inferences about changes in energetic metabolism (carbohydrate use and oxidative phosphorylation, which would not have been possible by taking a 'biomarker' approach to data analysis. Conclusion Multiple post-genomic techniques can be combined to provide mechanistic information about the toxic effects of chemical contaminants, even for non-model organisms with few additional mechanistic toxicological data. With 70-day no-observed-effect and lowest-observed-effect concentrations (NOEC and LOEC of 10 and 40 mg kg-1 for metabolomic and microarray profiles, copper is shown to interfere with energy metabolism in an important soil organism at an ecologically and functionally relevant level.

  3. A Coordinated Approach to Curricular Review and Development in Undergraduate Geoscience Programs: Using a Matrix to Identify and Track Skills and Skill Development

    Science.gov (United States)

    MacDonald, R.; Savina, M. E.

    2003-12-01

    assignment or activities. We have found that much conversation among faculty and change within courses happens simply as a result of compiling the matrix. One effect of the use of the matrix is that faculty in the department know fairly specifically what skills students are learning and practicing in their other geology courses. Moreover, some faculty members are better suited by background or inclination to teach certain sets of skills. This coordinated approach avoids unnecessary duplication and allows faculty to build on skills and topics developed in previous courses. The matrix can also be used as a planning tool to identify gaps in the curriculum. In our experience, the skills matrix is a powerful organizational and communication tool. The skills matrix is a representation of what the department believes actually happens in the curriculum. Thus, development of a skills matrix provides a basis for departmental discussions of student learning goals and objectives as well as for describing the existing curriculum. The matrix is also a graphic representation, to college administrators and outside evaluators, of the "intentionality" of an entire curriculum, going beyond single courses and their syllabi. It can be used effectively to engage administration in discussions of departmental planning and needs analysis.

  4. Recent developments in methods for identifying reaction coordinates.

    Science.gov (United States)

    Li, Wenjin; Ma, Ao

    2014-01-01

    In the study of rare events in complex systems with many degrees of freedom, a key element is to identify the reaction coordinates of a given process. Over recent years, a number of methods and protocols have been developed to extract the reaction coordinates based on limited information from molecular dynamics simulations. In this review, we provide a brief survey over a number of major methods developed in the past decade, some of which are discussed in greater detail, to provide an overview of the problems that are partially solved and challenges that still remain. A particular emphasis has been placed on methods for identifying reaction coordinates that are related to the committor.

  5. Recent Developments in Methods for Identifying Reaction Coordinates

    CERN Document Server

    Li, Wenjin

    2015-01-01

    In the study of rare events in complex systems with many degrees of freedom, a key element is to identify the reaction coordinates of a given process. Over recent years, a number of methods and protocols have been developed to extract the reaction coordinates based on limited information from molecular dynamics simulations. In this review, we provide a brief survey over a number of major methods developed in the past decade, some of which are discussed in greater detail, to provide an overview of the problems that are partially solved and challenges that still remain. A particular emphasis has been placed on methods for identifying reaction coordinates that are related to the committor.

  6. Coordination Approaches for Complex Software Systems

    NARCIS (Netherlands)

    Bosse, T.; Hoogendoorn, M.; Treur, J.

    2006-01-01

    This document presents the results of a collaboration between the Vrije Universiteit Amsterdam, Department of Artificial Intelligence and Force Vision to investigate coordination approaches for complex software systems. The project was funded by Force Vision.

  7. Stochastic learning in co-ordination games : a simulation approach

    OpenAIRE

    Zaninotto, Enrico; Rossi, Alessandro; Gaio, Loris

    1999-01-01

    In the presence of externalities, consumption behaviour depends on the solution of a co-ordination problem. In our paper we suggest a learning approach to the study of co-ordination in consumption contexts where agents adjust their choices on the basis of the reinforcement (payoff) they receive during the game. The results of simulations allowed us to distinguish the roles of different aspects of learning in enabling co-ordination within a population of agents. Our main results highlight: 1. ...

  8. A BARGAINING APPROACH TO COORDINATION IN NETWORKS

    OpenAIRE

    Miguel A. Meléndez-Jiménez

    2007-01-01

    This paper presents a model in which players interact via the formation of costly links and the benefits of bilateral interactions are determined by a coordination game. A novel contribution of this paper is that the fraction of the cost borne by each player involved in a bilateral link is not fixed exogenously, but results from bargaining. We analyze the model both in a static and a dynamic setting. Whereas the static game has multiplicity of equilibria, we show that only one is stochastical...

  9. Identifying Geographic Clusters: A Network Analytic Approach

    CERN Document Server

    Catini, Roberto; Penner, Orion; Riccaboni, Massimo

    2015-01-01

    In recent years there has been a growing interest in the role of networks and clusters in the global economy. Despite being a popular research topic in economics, sociology and urban studies, geographical clustering of human activity has often studied been by means of predetermined geographical units such as administrative divisions and metropolitan areas. This approach is intrinsically time invariant and it does not allow one to differentiate between different activities. Our goal in this paper is to present a new methodology for identifying clusters, that can be applied to different empirical settings. We use a graph approach based on k-shell decomposition to analyze world biomedical research clusters based on PubMed scientific publications. We identify research institutions and locate their activities in geographical clusters. Leading areas of scientific production and their top performing research institutions are consistently identified at different geographic scales.

  10. Crew coordination issues of EVS approaches

    Science.gov (United States)

    Lorenz, Bernd; Korn, Bernd R.

    2004-08-01

    Enhanced Vision Systems (EVS) are currently developed with the goal to alleviate restrictions in airspace and airport capacity in low visibility conditions. Existing EVS-systems are based on IR-sensors although the penetration of bad weather (dense fog and light rain) by MMW-radar is remarkably better than in the infrared spectrum. But the quality of MMW radar is rather poor compared to IR images. However, the analysis of radar images can be simplified dramatically when simple passive radar retro-reflectors are used to mark the runway. This presentation is the third in a series of studies investigating the use of such simple landing aids. In the first study the feasibility of the radar PAPI concept was determined; the second one provided first promising human performance results in a low-fidelity simulation. The present study examined pilot performance, workload, situation awareness, and crew coordination issues in a high-fidelity simulation of 'Radar-PAPI' visual aids supporting a precision straight-in landing in low visibility (CAT-II). Simulation scenarios were completed in a fixed-base cockpit simulator involving six two-pilot flight-deck crews. Pilots could derive visual cues to correct lateral glide-path deviations from 13 pairs of runway-marking corner reflectors. Vertical deviations were indicated by a set of six diplane reflectors using intensity-coding to provide the PAPI categories needed for the correction of vertical deviations. The study compared three display formats and associated crew coordination issues: (1) PF views a head-down B-scope display and switches to visual landing upon PNF's call-out that runway is in sight; (2) PF views a head-down C-scope display and switches to visual landing upon PNF's call-out that runway is in sight; (3) PF views through a head-up display (HUD) that displays primary flight guidance information and receives vertical and lateral guidance from PNF who views a head-down B-scope. PNF guidance is terminated upon PF

  11. Coordination between offshore transmission assets - A third way approach

    DEFF Research Database (Denmark)

    Silva, Filipe Miguel Faria da

    2014-01-01

    Offshore wind farms have been seen for several years as key for achieving the European targets on the use of renewable energies. The majority of offshore wind parks has been built without considering possible coordination between them, but as their number increases so does the benefits of coordin......Offshore wind farms have been seen for several years as key for achieving the European targets on the use of renewable energies. The majority of offshore wind parks has been built without considering possible coordination between them, but as their number increases so does the benefits...... of coordination between assets. This paper analyses the Ofgem’s document ”Consultation on a proposed framework to enable coordination of offshore transmission” and summarises its proposals. The developer-lead approach used in UK is compared with the TSO-lead approach used in Denmark, regarding potential...... coordination between offshore wind farms of different developers. The paper proposes a third approach, mixing the developer-lead and TSO-lead approaches. The main benefits and challenges of the proposed approach are presented, as well as future work....

  12. Coordination-theoretic approach to modelling grid service composition process

    Institute of Scientific and Technical Information of China (English)

    Meng Qian; Zhong Liu; Jing Wang; Li Yao; Weiming Zhang

    2010-01-01

    A grid service composite process is made up of complex coordinative activities.Developing the appropriate model of grid service coordinative activities is an important foundation for the grid service composition.According to the coordination theory,this paper elaborates the process of the grid service composition by using UML 2.0,and proposes an approach to modelling the grid service composition process based on the coordination theory.This approach helps not only to analyze accurately the task activities and relevant dependencies among task activities,but also to facilitate the adaptability of the grid service orchestration to further realize the connectivity,timeliness,appropriateness and expansibility of the grid service composition.

  13. Understanding confounding effects in linguistic coordination: an information-theoretic approach

    CERN Document Server

    Gao, Shuyang; Galstyan, Aram

    2014-01-01

    We suggest an information-theoretic approach for measuring linguistic style coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong sig- natures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect - length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors.

  14. Evolutionary Trends of Developer Coordination: A Network Approach

    OpenAIRE

    Joblin, Mitchell; Apel, Sven; Mauerer, Wolfgang

    2015-01-01

    Software evolution is a fundamental process that transcends the realm of technical artifacts and permeates the entire organizational structure of a software project. By means of a longitudinal empirical study of 18 large open-source projects, we examine and discuss the evolutionary principles that govern the coordination of developers. By applying a network-analytic approach, we found that the implicit and self-organizing structure of developer coordination is ubiquitously described by non-ra...

  15. Wind-CSP short-term coordination by MILP approach

    OpenAIRE

    Pousinho, Hugo Miguel Inácio; Silva, Hugo Alexandre Fernandes dos Santos e; Mendes, Víctor Manuel Fernandes; Collares-Pereira, M.; Cabrita, C. Pereira

    2014-01-01

    This paper is on the maximization of total profit in a day-ahead market for a price-taker producer needing a short-term scheduling for wind power plants coordination with concentrated solar power plants, having thermal energy storage systems. The optimization approach proposed for the maximization of profit is a mixed-integer linear programming problem. The approach considers not only transmission grid constraints, but also technical operating constraints on both wind and concentrated solar p...

  16. Dynamics of coupled field solitons: A collective coordinate approach

    Indian Academy of Sciences (India)

    Danial Saadatmand; Aliakbar Moradi Marjaneh; Mahdi Heidari

    2014-10-01

    In this paper we consider a class of systems of two coupled real scalar fields in bidimensional space-time, with the main motivation of studying classical stability of soliton solutions using collective coordinate approach. First, we present the class of systems of the collective coordinate equations which are derived using the presented method. After that, we follow the dynamics of the coupled fields with local inhomogeneity like a delta function potential wall as well as a delta function potential well. The results of the investigation of the two coupled fields are compared to each other and the differences are discussed. The method can predict most of the characters of the interaction.

  17. Sensitivity analysis approach to multibody systems described by natural coordinates

    Science.gov (United States)

    Li, Xiufeng; Wang, Yabin

    2014-03-01

    The classical natural coordinate modeling method which removes the Euler angles and Euler parameters from the governing equations is particularly suitable for the sensitivity analysis and optimization of multibody systems. However, the formulation has so many principles in choosing the generalized coordinates that it hinders the implementation of modeling automation. A first order direct sensitivity analysis approach to multibody systems formulated with novel natural coordinates is presented. Firstly, a new selection method for natural coordinate is developed. The method introduces 12 coordinates to describe the position and orientation of a spatial object. On the basis of the proposed natural coordinates, rigid constraint conditions, the basic constraint elements as well as the initial conditions for the governing equations are derived. Considering the characteristics of the governing equations, the newly proposed generalized-α integration method is used and the corresponding algorithm flowchart is discussed. The objective function, the detailed analysis process of first order direct sensitivity analysis and related solving strategy are provided based on the previous modeling system. Finally, in order to verify the validity and accuracy of the method presented, the sensitivity analysis of a planar spinner-slider mechanism and a spatial crank-slider mechanism are conducted. The test results agree well with that of the finite difference method, and the maximum absolute deviation of the results is less than 3%. The proposed approach is not only convenient for automatic modeling, but also helpful for the reduction of the complexity of sensitivity analysis, which provides a practical and effective way to obtain sensitivity for the optimization problems of multibody systems.

  18. A Rational Approach to Ring Flexibility in Internal Coordinate Dynamics

    CERN Document Server

    Mazur, A K

    1998-01-01

    Internal coordinate molecular dynamics (ICMD) is an efficient method for studying biopolymers, but it is readily applicable only to molecules with tree topologies, that is with no internal flexible rings. Common examples violating this condition are prolines and loops closed by S-S bridges in proteins. The most important such case, however, is nucleic acids because the flexibility of the furanose rings always plays an essential role in conformational transitions both in DNA and RNA. There are a few long-known theoretical approaches to this problem, but, in practice, rings with fixed bond lengths are closed by adding appropriate harmonic distance restraints, which is not always acceptable especially in dynamics. This paper tries to overcome this handicap of ICMD and proposes a rational strategy which results in practical numerical algorithms. It gives a unified analytical treatment which shows that this problem is very close to the difficulties encountered by the method of constraints in Cartesian coordinate d...

  19. Identifying Care Coordination Interventions Provided to Community-Dwelling Older Adults Using Electronic Health Records.

    Science.gov (United States)

    Kim, Tae Youn; Marek, Karen D; Coenen, Amy

    2016-07-01

    Although care coordination is a popular intervention, there is no standard method of delivery. Also little is known about who benefits most, or characteristics that predict the amount of care coordination needed, especially with chronically ill older adults. The purpose of this study was to identify types and amount of nurse care coordination interventions provided to 231 chronically ill older adults who participated in a 12-month home care medication management program in the Midwest. For each participant, the nurse care coordinator spent an average of 134 min/mo providing in-person home care, 48 min/mo of travel, and 18 min/mo of indirect care occurring outside the home visit. This accounted for 67.2%, 23.8%, and 9.0% of nursing time, respectively, for home visits, travel, and indirect care. Four of 11 nursing interventions focused on medication management were provided to all participants. Seven of the 11 main interventions were individualized according to each person's special needs. Wide variations were observed in time provided with in-person home care and communications with multiple stakeholders. Study findings indicate the importance of individualizing interventions and the variability in the amount of nursing time needed to provide care coordination to chronically ill older adults.

  20. Identifying Care Coordination Interventions Provided to Community-Dwelling Older Adults Using Electronic Health Records.

    Science.gov (United States)

    Kim, Tae Youn; Marek, Karen D; Coenen, Amy

    2016-07-01

    Although care coordination is a popular intervention, there is no standard method of delivery. Also little is known about who benefits most, or characteristics that predict the amount of care coordination needed, especially with chronically ill older adults. The purpose of this study was to identify types and amount of nurse care coordination interventions provided to 231 chronically ill older adults who participated in a 12-month home care medication management program in the Midwest. For each participant, the nurse care coordinator spent an average of 134 min/mo providing in-person home care, 48 min/mo of travel, and 18 min/mo of indirect care occurring outside the home visit. This accounted for 67.2%, 23.8%, and 9.0% of nursing time, respectively, for home visits, travel, and indirect care. Four of 11 nursing interventions focused on medication management were provided to all participants. Seven of the 11 main interventions were individualized according to each person's special needs. Wide variations were observed in time provided with in-person home care and communications with multiple stakeholders. Study findings indicate the importance of individualizing interventions and the variability in the amount of nursing time needed to provide care coordination to chronically ill older adults. PMID:26985762

  1. Identifying MMORPG Bots: A Traffic Analysis Approach

    Directory of Open Access Journals (Sweden)

    Wen-Chin Chen

    2008-11-01

    Full Text Available Massively multiplayer online role playing games (MMORPGs have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1 the regularity in the release time of client commands, 2 the trend and magnitude of traffic burstiness in multiple time scales, and 3 the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  2. Identifying MMORPG Bots: A Traffic Analysis Approach

    Science.gov (United States)

    Chen, Kuan-Ta; Jiang, Jhih-Wei; Huang, Polly; Chu, Hao-Hua; Lei, Chin-Laung; Chen, Wen-Chin

    2008-12-01

    Massively multiplayer online role playing games (MMORPGs) have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1) the regularity in the release time of client commands, 2) the trend and magnitude of traffic burstiness in multiple time scales, and 3) the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  3. An approach to identify urban groundwater recharge

    Directory of Open Access Journals (Sweden)

    E. Vázquez-Suñé

    2010-10-01

    Full Text Available Evaluating the proportion in which waters from different origins are mixed in a given water sample is relevant for many hydrogeological problems, such as quantifying total recharge, assessing groundwater pollution risks, or managing water resources. Our work is motivated by urban hydrogeology, where waters with different chemical signature can be identified (losses from water supply and sewage networks, infiltration from surface runoff and other water bodies, lateral aquifers inflows, .... The relative contribution of different sources to total recharge can be quantified by means of solute mass balances, but application is hindered by the large number of potential origins. Hence, the need to incorporate data from a large number of conservative species, the uncertainty in sources concentrations and measurement errors. We present a methodology to compute mixing ratios and end-members composition, which consists of (i Identification of potential recharge sources, (ii Selection of tracers, (iii Characterization of the hydrochemical composition of potential recharge sources and mixed water samples, and (iv Computation of mixing ratios and reevaluation of end-members. The analysis performed in a data set from samples of the Barcelona city aquifers suggests that the main contributors to total recharge are the water supply network losses (22%, the sewage network losses (30%, rainfall, concentrated in the non-urbanized areas (17%, from runoff infiltration (20%, and the Besòs River (11%. Regarding species, halogens (chloride, fluoride and bromide, sulfate, total nitrogen, and stable isotopes (18O, 2H, and 34S behaved quite conservatively. Boron, residual alkalinity, EDTA and Zn did not. Yet, including these species in the computations did not affect significantly the proportion estimations.

  4. An approach to identify urban groundwater recharge

    Directory of Open Access Journals (Sweden)

    E. Vázquez-Suñé

    2010-04-01

    Full Text Available Evaluating the proportion in which waters from different origins are mixed in a given water sample is relevant for many hydrogeological problems, such as quantifying total recharge, assessing groundwater pollution risks, or managing water resources. Our work is motivated by urban hydrogeology, where waters with different chemical signature can be identified (losses from water supply and sewage networks, infiltration from surface runoff and other water bodies, lateral aquifers inflows, .... The relative contribution of different sources to total recharge can be quantified by means of solute mass balances, but application is hindered by the large number of potential origins. Hence, the need to incorporate data from a large number of conservative species, the uncertainty in sources concentrations and measurement errors. We present a methodology to compute mixing ratios and end-members composition, which consists of (i Identification of potential recharge sources, (ii Selection of tracers, (iii Characterization of the hydrochemical composition of potential recharge sources and mixed water samples, and (iv Computation of mixing ratios and reevaluation of end-members. The analysis performed in a data set from samples of the Barcelona city aquifers suggests that the main contributors to total recharge are the water supply network losses (22%, the sewage network losses (30%, rainfall, concentrated in the non-urbanized areas (17%, from runoff infiltration (20%, and the Besòs River (11%. Regarding species, halogens (chloride, fluoride and bromide, sulfate, total nitrogen, and stable isotopes (18O2H, and 34S behaved quite conservatively. Boron, residual alkalinity, EDTA and Zn did not. Yet, including these species in the computations did not affect significantly the proportion estimations.

  5. Mapping the Generator Coordinate Method to the Coupled Cluster Approach

    CERN Document Server

    Stuber, Jason L

    2015-01-01

    The generator coordinate method (GCM) casts the wavefunction as an integral over a weighted set of non-orthogonal single determinantal states. In principle this representation can be used like the configuration interaction (CI) or shell model to systematically improve the approximate wavefunction towards an exact solution. In practice applications have generally been limited to systems with less than three degrees of freedom. This bottleneck is directly linked to the exponential computational expense associated with the numerical projection of broken symmetry Hartree-Fock (HF) or Hartree-Fock-Bogoliubov (HFB) wavefunctions and to the use of a variational rather than a bi-variational expression for the energy. We circumvent these issues by choosing a hole-particle representation for the generator and applying algebraic symmetry projection, via the use of tensor operators and the invariant mean (operator average). The resulting GCM formulation can be mapped directly to the coupled cluster (CC) approach, leading...

  6. Energy Management in Prosumer Communities: A Coordinated Approach

    Directory of Open Access Journals (Sweden)

    Rodrigo Verschae

    2016-07-01

    Full Text Available The introduction of uncontrollable renewable energy is having a positive impact on our health, the climate, and the economy, but it is also pushing the limits of the power system. The main reason for this is that, in any power system, the generation and consumption must match each other at all times. Thus, if we want to further introduce uncontrollable generation, we need a large ability to manage the demand. However, the ability to control the power consumption of existing demand management approaches is limited, and most of these approaches cannot contribute to the introduction of reneweables, because they do not consider distributed uncontrolled consumption and generation in the control. Furthermore, these methods do not allow users to exchange or jointly manage their power generation and consumption. In this context, we propose an augmented energy management model for prosumers (i.e., producer and consumer. This model considers controlled and uncontrolled generation and consumption, as well as the prosumer’s ability (i to plan the intended power consumption; and (ii to manage real-time deviations from the intended consumption. We apply this model to the energy management of prosumer communities, by allowing the prosumers to coordinate their power consumption plan, to manage the deviations from the intended consumption, and to help each other by compensating deviations. The proposed approach seeks to enhance the power system, and to enable a prosumer society that takes account social and environmental issues, as well as each prosumer’s quality of life.

  7. Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function.

    NARCIS (Netherlands)

    Fliers, E.A.; Arias Vasquez, A.; Poelmans, G.J.V.; Rommelse, N.N.; Altink, M.E.; Buschgens, C.J.M.; Asherson, P.; Banaschewski, T.; Ebstein, R.; Gill, M.; Miranda, A.; Mulas, F.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.S.J.; Steinhausen, H.C.; Faraone, S.V.; Buitelaar, J.K.; Franke, B.

    2012-01-01

    OBJECTIVES: Motor coordination problems are frequent in children with attention deficit/hyperactivity disorder (ADHD). We performed a genome-wide association study to identify genes contributing to motor coordination problems, hypothesizing that the presence of such problems in children with ADHD ma

  8. Drosophila Imp iCLIP identifies an RNA assemblage coordinating F-actin formation

    DEFF Research Database (Denmark)

    Hansen, Heidi Theil; Rasmussen, Simon Horskjær; Adolph, Sidsel Kramshøj;

    2015-01-01

    CLIP) technologies in Drosophila cells to identify transcripts associated with cytoplasmic ribonucleoproteins (RNPs) containing the RNA-binding protein Imp. RESULTS: We find extensive binding of Imp to 3'UTRs of transcripts that are involved in F-actin formation. A common denominator of the RNA-protein interface....... This demonstrates a physiological significance of the defined RNA regulon. CONCLUSIONS: Our data imply that Drosophila Imp RNPs may function as cytoplasmic mRNA assemblages that encode proteins which participate in actin cytoskeletal remodeling. Thus, they may facilitate co-ordinated protein expression in sub...... is the presence of multiple motifs with a central UA-rich element flanked by CA-rich elements. Experiments in single cells and intact flies reveal compromised actin cytoskeletal dynamics associated with low Imp levels. The former shows reduced F-actin formation and the latter exhibits abnormal neuronal patterning...

  9. Low-income DSM Programs: Methodological approach to determining the cost-effectiveness of coordinated partnerships

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.A.; Hill, L.J.

    1994-05-01

    As governments at all levels become increasingly budget-conscious, expenditures on low-income, demand-side management (DSM) programs are being evaluated more on the basis of efficiency at the expense of equity considerations. Budgetary pressures have also caused government agencies to emphasize resource leveraging and coordination with electric and gas utilities as a means of sharing the expenses of low-income programs. The increased involvement of electric and gas utilities in coordinated low-income DSM programs, in turn, has resulted in greater emphasis on estimating program cost-effectiveness. The objective of this study is to develop a methodological approach to estimate the cost- effectiveness of coordinated low-income DSM programs, given the special features that distinguish these programs from other utility-operated DSM programs. The general approach used in this study was to (1) select six coordinated low-income DSM programs from among those currently operating across the United States, (2) examine the main features of these programs, and (3) determine the conceptual and pragmatic problems associated with estimating their cost-effectiveness. Three types of coordination between government and utility cosponsors were identified. At one extreme, local agencies operate {open_quotes}parallel{close_quotes} programs, each of which is fully funded by a single sponsor (e.g., one funded by the U.S. Department of Energy and the other by a utility). At the other extreme are highly {open_quotes}coupled{close_quotes} programs that capitalize on the unique capabilities and resources offered by each cosponsor. In these programs, agencies employ a combination of utility and government funds to deliver weatherization services as part of an integrated effort. In between are {open_quotes}supplemental{close_quotes} programs that utilize resources to supplement the agency`s government-funded weatherization, with no changes to the operation of that program.

  10. The Approach to Steady State Using Homogeneous and Cartesian Coordinates

    Directory of Open Access Journals (Sweden)

    D. F. Gochberg

    2013-01-01

    Full Text Available Repeating an arbitrary sequence of RF pulses and magnetic field gradients will eventually lead to a steady-state condition in any magnetic resonance system. While numerical methods can quantify this trajectory, analytic analysis provides significantly more insight and a means for faster calculation. Recently, an analytic analysis using homogeneous coordinates was published. The current work further develops this line of thought and compares the relative merits of using a homogeneous or a Cartesian coordinate system.

  11. Using a polyphasic approach to identify wild Brazilian fungal strains

    OpenAIRE

    Lima, M. Sanitá; Santos, C.; Lima, Nelson; Maria de Lourdes T. M. Polizeli

    2012-01-01

    [Aim] The species must be delineated based on a polyphasic approach, including morphology, physiology, profile of secondary metabolites and molecular biology [1]. According to Santos et al. [2;3] it is clearer that spectral analyses add value to the polyphasic approach. This work aimed to perform a polyphasic approach based on morphological, biochemical and spectral analysis by MALDI-TOF ICMS for identify Aspergilli isolates from different environments of Brazil.

  12. A review of five tests to identify motor coordination difficulties in young adults.

    Science.gov (United States)

    Hands, Beth; Licari, Melissa; Piek, Jan

    2015-01-01

    Difficulties with low motor competence in childhood and adolescence, such as that seen in Developmental Coordination Disorder (DCD), often persist into adulthood. Identification of DCD at all ages is particularly challenging and problematic because of the diversity of motor symptoms. Many tests of motor proficiency and impairment have been developed for children up to 12 years of age. Whilst identification of DCD is important during childhood, it is of equal importance to identify and monitor the impact of this impairment as an individual grows and develops. Currently there is no test specifically designed to support diagnosis and monitor change in the age range 16-30 years. In this article we review five tests that have been used to assess motor competence among young adults (Bruininks-Oseretsky Test of Motor Proficiency-2, McCarron Assessment of Neuromuscular Development, Movement Assessment Battery for Children-2, Tufts Assessment of Motor Performance and the Zurich Neuromotor Assessment). Key issues relevant to testing motor skills in older populations, such as the inclusion of age appropriate skills, are explored. While the BOT-2 provided the most evidence for valid and reliable measurement of Criterion A of the diagnostic criteria for DCD among this age group, no test adequately evaluated Criterion B. Further evaluation of motor skill assessment among the young adult population is needed.

  13. Utilizing Distributed Resources in Smart Grids - A Coordination Approach

    DEFF Research Database (Denmark)

    Juelsgaard, Morten

    2014-01-01

    as well as its limitations. Enforcing coordination through temporal shifts of consumption and production requires the problems we consider to be solved across some predefined time-horizon. Utilizing flexibility of consumers through coordination, is known as demand management, and considers how consumers...... of power if the flow reverses on account of residential production. The focus of this thesis is to show that proper utilization and coordination of distributed resources in the grid can be an important tool to alleviate these challenges. We initially elaborate on the expected challenges, where we focus...... specifically on grid balancing, congestion management, minimization of transport losses, and control of power quality. Subsequently, we discuss various classes of resources in the grid and introduce the concept of a smart grid, within which we derive optimization strategies to demonstrate the resources...

  14. Covert Flow Graph Approach to Identifying Covert Channels

    Directory of Open Access Journals (Sweden)

    XiangMei Song

    2011-12-01

    Full Text Available In this paper, the approach for identifying covert channels using a graph structure called Covert Flow Graph is introduced. Firstly, the construction of Covert Flow Graph which can offer information flows of the system for covert channel detection is proposed, and the search and judge algorithm used to identify covert channels in Covert Flow Graph is given. Secondly, an example file system analysis using Covert Flow Graph approach is provided, and the analysis result is compared with that of Shared Resource Matrix and Covert Flow Tree method. Finally, the comparison between Covert Flow Graph approach and other two methods is discussed. Different from previous methods, Covert Flow Graph approach provides a deep insight for system’s information flows, and gives an effective algorithm for covert channel identification.

  15. Coordinated aggregation in complex systems:. an interdisciplinary approach

    Science.gov (United States)

    Basios, V.; Nicolis, S. C.; Deneubourg, J. L.

    2016-09-01

    The study of the topic of guided aggregation in biology brings together decision making, collective motion and the dynamical interplay between individuals and groups. At the same time it meets statistical mechanics and the physics of complex systems in a new paradigmatic thinking. We propose a research platform for implementation and for undertaking systematic studies of coordinated aggregation, in a truly multi- and inter-disciplinary fashion.

  16. Coordinate independent approach to 5d black holes

    CERN Document Server

    Didenko, V E

    2011-01-01

    Five-dimensional generalization of (A)dS(5)-Kerr black hole is shown to be generated in a coordinate free way by a single AdS(5) global symmetry parameter. Its mass and angular momenta are associated to Casimir invariants of the background space-time symmetry parameter leading to the black hole classification scheme similar to that of relativistic fields resulting apart from ordinary black hole to "tachyonic" and "light-like" ones.

  17. Learning to Coordinate Efficiently: A Model-based Approach

    CERN Document Server

    Brafman, R I; 10.1613/jair.1154

    2011-01-01

    In common-interest stochastic games all players receive an identical payoff. Players participating in such games must learn to coordinate with each other in order to receive the highest-possible value. A number of reinforcement learning algorithms have been proposed for this problem, and some have been shown to converge to good solutions in the limit. In this paper we show that using very simple model-based algorithms, much better (i.e., polynomial) convergence rates can be attained. Moreover, our model-based algorithms are guaranteed to converge to the optimal value, unlike many of the existing algorithms.

  18. Game-theoretic interference coordination approaches for dynamic spectrum access

    CERN Document Server

    Xu, Yuhua

    2016-01-01

    Written by experts in the field, this book is based on recent research findings in dynamic spectrum access for cognitive radio networks. It establishes a game-theoretic framework and presents cutting-edge technologies for distributed interference coordination. With game-theoretic formulation and the designed distributed learning algorithms, it provides insights into the interactions between multiple decision-makers and the converging stable states. Researchers, scientists and engineers in the field of cognitive radio networks will benefit from the book, which provides valuable information, useful methods and practical algorithms for use in emerging 5G wireless communication.

  19. Coordination between Subway and Urban Space: A Networked Approach

    Directory of Open Access Journals (Sweden)

    Lei Mao

    2014-05-01

    Full Text Available This paper selects Changsha as a case study and constructs the models of the subway network and the urban spatial network by using planning data. In the network models, the districts of Changsha are regarded as nodes and the connections between each pair of districts are regarded as edges. The method is based on quantitative analysis of the node weights and the edge weights, which are defined in the complex network theory. And the structures of subway and urban space are visualized in the form of networks. Then, through analyzing the discrepancy coefficients of the corresponding nodes and edges, the paper carries out a comparison between the two networks to evaluate the coordination. The results indicate that only 21.4% of districts and 13.2% of district connections have a rational coordination. Finally, the strategies are put forward for optimization, which suggest adjusting subway transit density, regulating land-use intensity and planning new mass transits for the uncoordinated parts.

  20. Large screen approaches to identify novel malaria vaccine candidates.

    Science.gov (United States)

    Davies, D Huw; Duffy, Patrick; Bodmer, Jean-Luc; Felgner, Philip L; Doolan, Denise L

    2015-12-22

    Until recently, malaria vaccine development efforts have focused almost exclusively on a handful of well characterized Plasmodium falciparum antigens. Despite dedicated work by many researchers on different continents spanning more than half a century, a successful malaria vaccine remains elusive. Sequencing of the P. falciparum genome has revealed more than five thousand genes, providing the foundation for systematic approaches to discover candidate vaccine antigens. We are taking advantage of this wealth of information to discover new antigens that may be more effective vaccine targets. Herein, we describe different approaches to large-scale screening of the P. falciparum genome to identify targets of either antibody responses or T cell responses using human specimens collected in Controlled Human Malaria Infections (CHMI) or under conditions of natural exposure in the field. These genome, proteome and transcriptome based approaches offer enormous potential for the development of an efficacious malaria vaccine. PMID:26428458

  1. Population planning: a well co-ordinated approach required.

    Science.gov (United States)

    1984-01-01

    This discussion combines information obtained from 5 countries in the Economic and Social Commission for Asia and the Pacific (ESCAP) region on the role of population planning in the context of integrated policies and programs. The countries were asked what specific aspects of the present population policy and program would require concentrated inputs in order to achieve stated goals and targets. In Indonesia 2 program areas are identified for intensification: the organized transmigration scheme which aims at a balanced distribution of population and exploitation of potential resources throughout the country, including islands outside Java and Bali; and the national family planning program as a whole, in order to achieve the target of 60% prevalence rate of contraceptive use among eligible couples in 1990 and a decline of the crude birthrate from 33/1000 to 23/1000 by that date. Both programs are receiving high priority. Nepal policy and programs are aimed at achieving replacement level fertility by 2000. Steps that have been initiated in Bangladesh include intensive motivation activities with strong media inputs, the maintenance of a regular and adequate supply of contraceptives at the doorstep of clients, and strengthening the multisectoral program. The Philippines National Population Program advocates and promotes 4 norms in order to achieve a population growth rate of 2%, a prevalence rate of 54%, and contraceptive effectiveness of 80% by 1987: small family size; birth spacing; delayed marriages; and reduced incidence of teenage pregnancies. The goals envisaged for India are a reduction in the crude birthrate to not more than 21/1000, crude death rate of not more than 9/1000, and an infant mortality rate of less than 60/1000 live births by 2000. Concentrated efforts will be needed in the use of mass media and interpersonal communication strategies with services and supplies being provided as close to the doorstep of the acceptor as possible. In most countries

  2. Identifying acute coronary syndrome patients approaching end-of-life.

    Directory of Open Access Journals (Sweden)

    Stephen Fenning

    Full Text Available BACKGROUND: Acute coronary syndrome (ACS is common in patients approaching the end-of-life (EoL, but these patients rarely receive palliative care. We compared the utility of a palliative care prognostic tool (Gold Standards Framework (GSF and the Global Registry of Acute Coronary Events (GRACE score, to help identify patients approaching EoL. METHODS AND FINDINGS: 172 unselected consecutive patients with confirmed ACS admitted over an eight-week period were assessed using prognostic tools and followed up for 12 months. GSF criteria identified 40 (23% patients suitable for EoL care while GRACE identified 32 (19% patients with ≥ 10% risk of death within 6 months. Patients meeting GSF criteria were older (p = 0.006, had more comorbidities (1.6 ± 0.7 vs. 1.2 ± 0.9, p = 0.007, more frequent hospitalisations before (p = 0.001 and after (0.0001 their index admission, and were more likely to die during follow-up (GSF+ 20% vs GSF- 7%, p = 0.03. GRACE score was predictive of 12-month mortality (C-statistic 0.75 and this was improved by the addition of previous hospital admissions and previous history of stroke (C-statistic 0.88. CONCLUSIONS: This study has highlighted a potentially large number of ACS patients eligible for EoL care. GSF or GRACE could be used in the hospital setting to help identify these patients. GSF identifies ACS patients with more comorbidity and at increased risk of hospital readmission.

  3. New Geo-location Approach Based on Camera Coordinates and Common Points on Multiple Images

    Directory of Open Access Journals (Sweden)

    Yu Jiaxiang

    2009-01-01

    Full Text Available The accuracy of traditional unmanned aerial vehicle (UAV geo-location based on single image is too low to meet the needs of precise strike. In this paper, a new UAV geo-location method is presented. The mathematical models are constructed by linearization of the collinearity equations to iteratively compute the pose angles and focal length of the camera. At least three images of the target, along with at least three identifiable common points among the images, are needed for reckoning camera pose angles and focal length. The three dimensional (3D coordinates of ground target are calculated using forward intersection. The new method can get the target coordinates with no dependence on digital elevation model (DEM and the measured values of camera pose angles, therefore two of the three primary error sources in the traditional UAV target location approach are eliminated. Simulation and real image experiment results show that the accuracy of the estimated target location is close to that of the UAV position, and that target location error is within 5m circular error probable (CEP on condition that the UAV is navigated by differential global positioning systems (DGPS.Defence Science Journal, 2009, 59(1, pp.43-48, DOI:http://dx.doi.org/10.14429/dsj.59.1483

  4. Contemporary Approaches for Identifying Rare Bone Disease Causing Genes

    Institute of Scientific and Technical Information of China (English)

    Charles R.Farber; Thomas L.Clemens

    2013-01-01

    Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti-cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.

  5. 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.

  6. A mobile-agent-based approach to software coordination inthe HOOPE system

    Institute of Scientific and Technical Information of China (English)

    马晓星; 吕建; 陶先平; 李英军; 胡昊

    2002-01-01

    Software coordination is central to the construction of large-scale high-performance distributed applications with software services scattered over the decentralized Internet. In this paper, a new mobile-agent-based architecture is proposed for the utilization and coordination of geographically distributed computing resources. Under this architecture, a user application is built with a set of software agents that can travel across the network autonomously. These agents utilize the distributed resources and coordinate with each other to complete their task. This approach's advantages include the natural expression and flexible deployment of the coordination logic, the dynamic adaptation to the network environment and the potential of better application performance. This coordination architecture, together with an object-oriented hierarchical parallel application framework and a graphical application construction tool, is implemented in the HOOPE environment, which provides a systematic support for the development and execution of Internet-based distributed and parallel applications in the petroleum exploration industry.

  7. Distribution Free Approach for Coordination of a Supply Chain with Consumer Return

    Science.gov (United States)

    Hu, Jinsong; Xu, Yuanji

    Consumer return is considered in a coordination of a supply chain consisting of one manufacturer and one retailer. A distribution free approach is employed to deal with a centralized decision model and a decentralized model which are constructed under the situation with only knowing the demand function's mean and variance, respectively. A markdown money contract is designed to coordinate the supply chain, and it is also proved that the contract can make the supply chain perfectly coordinated. Several numerical examples are given at the end of this paper.

  8. A computational approach for identifying pathogenicity islands in prokaryotic genomes

    Directory of Open Access Journals (Sweden)

    Oh Tae Kwang

    2005-07-01

    Full Text Available Abstract Background Pathogenicity islands (PAIs, distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs that have been acquired by horizontal gene transfer event. Up to now, computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage. These approaches often lead to the identification of genomic islands, rather than PAIs. Results We present a computational method for detecting potential PAIs in complete prokaryotic genomes by combining sequence similarities and abnormalities in genomic composition. We first collected 207 GenBank accessions containing either part or all of the reported PAI loci. In sequenced genomes, strips of PAI-homologs were defined based on the proximity of the homologs of genes in the same PAI accession. An algorithm reminiscent of sequence-assembly procedure was then devised to merge overlapping or adjacent genomic strips into a large genomic region. Among the defined genomic regions, PAI-like regions were identified by the presence of homolog(s of virulence genes. Also, GIs were postulated by calculating G+C content anomalies and codon usage bias. Of 148 prokaryotic genomes examined, 23 pathogenic and 6 non-pathogenic bacteria contained 77 candidate PAIs that partly or entirely overlap GIs. Conclusion Supporting the validity of our method, included in the list of candidate PAIs were thirty four PAIs previously identified from genome sequencing papers. Furthermore, in some instances, our method was able to detect entire PAIs for those only partial sequences are available. Our method was proven to be an efficient method for demarcating the potential PAIs in our study. Also, the function(s and origin(s of a candidate PAI can be inferred by investigating the PAI queries comprising it. Identification and analysis of potential PAIs in prokaryotic

  9. Identifying low-coordinated atoms on oxide-supported Au clusters

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Xiao; Nilius, Niklas; Freund, Hans-Joachim [Fritz-Haber-Institut der MPG, Faradayweg 4-6, D-14195 Berlin (Germany); Koskinen, Pekka; Haekkinen, Hannu [Department of Physics, University of Jyvaeskylae, Finland (Finland)

    2010-07-01

    The outstanding chemical properties of small metal particles are partly governed by the perimeter atoms that are located at the boundary to the oxide support. Those edge and corner sites are unique due to their low coordination, a peculiar electronic structure and charge state. We have employed STM and DFT to characterize the perimeter atoms around planar Au clusters grown on a MgO/Ag(001) thin film. The atoms exhibit an enhanced state density with respect to the island center in conductance spectra taken around the Fermi level. Furthermore, they carry extra electrons resulting from a charge transfer from the MgO-Ag interface into the Au islands. Both effects render the perimeter atoms highly attractive for binding molecules, as demonstrated via CO adsorption experiments on the system.

  10. A thermodynamic approach for identifying the conditions for gasless detonation

    Energy Technology Data Exchange (ETDEWEB)

    Gheribi, Aïmen E., E-mail: aimen.gheribi@polymtl.ca [Center for Research in Computational Thermochemistry, Department of Chemical Eng., École Polytechnique de Montréal, QC (Canada); Lee, Julian J. [Defence Research and Development Canada – Suffield, Suffield, AB (Canada); Thibault, Paul [TimeScales Scientific Ltd., Medicine Hat, AB (Canada)

    2015-01-15

    The present paper describes a theoretical method of examining thermodynamic equilibrium detonation states for reactions producing little or no gaseous products. Calculation of Phase Diagram (CALPHAD) techniques are used to calculate the thermodynamic states of the condensed-phase reaction at ambient conditions, and an analytical shock physics approach is used to estimate the detonation state. This method provides more accurate thermo–chemical equilibrium calculations for low-gas reactive mixtures, and can help evaluate the ability of a mixture to support a gasless detonation. A representative analysis was performed on an iron–aluminum thermite mixture and significant differences were found compared to previously published results. - Highlights: • A new CALPHAD method is used to identify optimal condition for gasless detonation. • The FactSage software and databases are used to calculate the materials properties. • The optimal detonation compositions are presented and discussed.

  11. Novel approaches to identify protective malaria vaccine candidates

    Directory of Open Access Journals (Sweden)

    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  12. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    Science.gov (United States)

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  13. FENICIA: a generic plasma simulation code using a flux-independent field-aligned coordinate approach

    International Nuclear Information System (INIS)

    The primary thrust of this work is the development and implementation of a new approach to the problem of field-aligned coordinates in magnetized plasma turbulence simulations called the FCI approach (Flux-Coordinate Independent). The method exploits the elongated nature of micro-instability driven turbulence which typically has perpendicular scales on the order of a few ion gyro-radii, and parallel scales on the order of the machine size. Mathematically speaking, it relies on local transformations that align a suitable coordinate to the magnetic field to allow efficient computation of the parallel derivative. However, it does not rely on flux coordinates, which permits discretizing any given field on a regular grid in the natural coordinates such as (x, y, z) in the cylindrical limit. The new method has a number of advantages over methods constructed starting from flux coordinates, allowing for more flexible coding in a variety of situations including X-point configurations. In light of these findings, a plasma simulation code FENICIA has been developed based on the FCI approach with the ability to tackle a wide class of physical models. The code has been verified on several 3D test models. The accuracy of the approach is tested in particular with respect to the question of spurious radial transport. Tests on 3D models of the drift wave propagation and of the Ion Temperature Gradient (ITG) instability in cylindrical geometry in the linear regime demonstrate again the high quality of the numerical method. Finally, the FCI approach is shown to be able to deal with an X-point configuration such as one with a magnetic island with good convergence and conservation properties. (author)

  14. Identifying Coordination Problems in Software Development: Finding Mismatches between Software and Project Team Structures

    CERN Document Server

    Amrit, Chintan; Kumar, Kuldeep

    2012-01-01

    Today's dynamic and iterative development environment brings significant challenges for software project management. In distributed project settings, "management by walking around" is no longer an option and project managers may miss out on key project insights. The TESNA (TEchnical Social Network Analysis) method and tool aims to provide project managers both a method and a tool for gaining insights and taking corrective action. TESNA achieves this by analysing a project's evolving social and technical network structures using data from multiple sources, including CVS, email and chat repositories. Using pattern theory, TESNA helps to identify areas where the current state of the project's social and technical networks conflicts with what patterns suggest. We refer to such a conflict as a Socio-Technical Structure Clash (STSC). In this paper we report on our experience of using TESNA to identify STSCs in a corporate environment through the mining of software repositories. We find multiple instances of three S...

  15. Identifying perinatal risk factors for infant maltreatment: an ecological approach

    Directory of Open Access Journals (Sweden)

    Hallisey Elaine J

    2006-12-01

    Full Text Available Abstract Background Child maltreatment and its consequences are a persistent problem throughout the world. Public health workers, human services officials, and others are interested in new and efficient ways to determine which geographic areas to target for intervention programs and resources. To improve assessment efforts, selected perinatal factors were examined, both individually and in various combinations, to determine if they are associated with increased risk of infant maltreatment. State of Georgia birth records and abuse and neglect data were analyzed using an area-based, ecological approach with the census tract as a surrogate for the community. Cartographic visualization suggested some correlation exists between risk factors and child maltreatment, so bivariate and multivariate regression were performed. The presence of spatial autocorrelation precluded the use of traditional ordinary least squares regression, therefore a spatial regression model coupled with maximum likelihood estimation was employed. Results Results indicate that all individual factors or their combinations are significantly associated with increased risk of infant maltreatment. The set of perinatal risk factors that best predicts infant maltreatment rates are: mother smoked during pregnancy, families with three or more siblings, maternal age less than 20 years, births to unmarried mothers, Medicaid beneficiaries, and inadequate prenatal care. Conclusion This model enables public health to take a proactive stance, to reasonably predict areas where poor outcomes are likely to occur, and to therefore more efficiently allocate resources. U.S. states that routinely collect the variables the National Center for Health Statistics (NCHS defines for birth certificates can easily identify areas that are at high risk for infant maltreatment. The authors recommend that agencies charged with reducing child maltreatment target communities that demonstrate the perinatal risks

  16. Lyapunov-based Low-thrust Optimal Orbit Transfer: An approach in Cartesian coordinates

    CERN Document Server

    Zhang, Hantian; Cao, Qingjie

    2014-01-01

    This paper presents a simple approach to low-thrust optimal-fuel and optimal-time transfer problems between two elliptic orbits using the Cartesian coordinates system. In this case, an orbit is described by its specific angular momentum and Laplace vectors with a free injection point. Trajectory optimization with the pseudospectral method and nonlinear programming are supported by the initial guess generated from the Chang-Chichka-Marsden Lyapunov-based transfer controller. This approach successfully solves several low-thrust optimal problems. Numerical results show that the Lyapunov-based initial guess overcomes the difficulty in optimization caused by the strong oscillation of variables in the Cartesian coordinates system. Furthermore, a comparison of the results shows that obtaining the optimal transfer solution through the polynomial approximation by utilizing Cartesian coordinates is easier than using orbital elements, which normally produce strongly nonlinear equations of motion. In this paper, the Eart...

  17. A geometric approach to identify cavities in particle systems

    Science.gov (United States)

    Voyiatzis, Evangelos; Böhm, Michael C.; Müller-Plathe, Florian

    2015-11-01

    The implementation of a geometric algorithm to identify cavities in particle systems in an open-source python program is presented. The algorithm makes use of the Delaunay space tessellation. The present python software is based on platform-independent tools, leading to a portable program. Its successful execution provides information concerning the accessible volume fraction of the system, the size and shape of the cavities and the group of atoms forming each of them. The program can be easily incorporated into the LAMMPS software. An advantage of the present algorithm is that no a priori assumption on the cavity shape has to be made. As an example, the cavity size and shape distributions in a polyethylene melt system are presented for three spherical probe particles. This paper serves also as an introductory manual to the script. It summarizes the algorithm, its implementation, the required user-defined parameters as well as the format of the input and output files. Additionally, we demonstrate possible applications of our approach and compare its capability with the ones of well documented cavity size estimators.

  18. Identifying predictors of physics item difficulty: A linear regression approach

    Science.gov (United States)

    Mesic, Vanes; Muratovic, Hasnija

    2011-06-01

    Large-scale assessments of student achievement in physics are often approached with an intention to discriminate students based on the attained level of their physics competencies. Therefore, for purposes of test design, it is important that items display an acceptable discriminatory behavior. To that end, it is recommended to avoid extraordinary difficult and very easy items. Knowing the factors that influence physics item difficulty makes it possible to model the item difficulty even before the first pilot study is conducted. Thus, by identifying predictors of physics item difficulty, we can improve the test-design process. Furthermore, we get additional qualitative feedback regarding the basic aspects of student cognitive achievement in physics that are directly responsible for the obtained, quantitative test results. In this study, we conducted a secondary analysis of data that came from two large-scale assessments of student physics achievement at the end of compulsory education in Bosnia and Herzegovina. Foremost, we explored the concept of “physics competence” and performed a content analysis of 123 physics items that were included within the above-mentioned assessments. Thereafter, an item database was created. Items were described by variables which reflect some basic cognitive aspects of physics competence. For each of the assessments, Rasch item difficulties were calculated in separate analyses. In order to make the item difficulties from different assessments comparable, a virtual test equating procedure had to be implemented. Finally, a regression model of physics item difficulty was created. It has been shown that 61.2% of item difficulty variance can be explained by factors which reflect the automaticity, complexity, and modality of the knowledge structure that is relevant for generating the most probable correct solution, as well as by the divergence of required thinking and interference effects between intuitive and formal physics knowledge

  19. Identifying predictors of physics item difficulty: A linear regression approach

    Directory of Open Access Journals (Sweden)

    Hasnija Muratovic

    2011-06-01

    Full Text Available Large-scale assessments of student achievement in physics are often approached with an intention to discriminate students based on the attained level of their physics competencies. Therefore, for purposes of test design, it is important that items display an acceptable discriminatory behavior. To that end, it is recommended to avoid extraordinary difficult and very easy items. Knowing the factors that influence physics item difficulty makes it possible to model the item difficulty even before the first pilot study is conducted. Thus, by identifying predictors of physics item difficulty, we can improve the test-design process. Furthermore, we get additional qualitative feedback regarding the basic aspects of student cognitive achievement in physics that are directly responsible for the obtained, quantitative test results. In this study, we conducted a secondary analysis of data that came from two large-scale assessments of student physics achievement at the end of compulsory education in Bosnia and Herzegovina. Foremost, we explored the concept of “physics competence” and performed a content analysis of 123 physics items that were included within the above-mentioned assessments. Thereafter, an item database was created. Items were described by variables which reflect some basic cognitive aspects of physics competence. For each of the assessments, Rasch item difficulties were calculated in separate analyses. In order to make the item difficulties from different assessments comparable, a virtual test equating procedure had to be implemented. Finally, a regression model of physics item difficulty was created. It has been shown that 61.2% of item difficulty variance can be explained by factors which reflect the automaticity, complexity, and modality of the knowledge structure that is relevant for generating the most probable correct solution, as well as by the divergence of required thinking and interference effects between intuitive and formal

  20. Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions.

    Science.gov (United States)

    Mahfouz, Ahmed; Lelieveldt, Boudewijn P F; Grefhorst, Aldo; van Weert, Lisa T C M; Mol, Isabel M; Sips, Hetty C M; van den Heuvel, José K; Datson, Nicole A; Visser, Jenny A; Reinders, Marcel J T; Meijer, Onno C

    2016-03-01

    Steroid receptors are pleiotropic transcription factors that coordinate adaptation to different physiological states. An important target organ is the brain, but even though their effects are well studied in specific regions, brain-wide steroid receptor targets and mediators remain largely unknown due to the complexity of the brain. Here, we tested the idea that novel aspects of steroid action can be identified through spatial correlation of steroid receptors with genome-wide mRNA expression across different regions in the mouse brain. First, we observed significant coexpression of six nuclear receptors (NRs) [androgen receptor (Ar), estrogen receptor alpha (Esr1), estrogen receptor beta (Esr2), glucocorticoid receptor (Gr), mineralocorticoid receptor (Mr), and progesterone receptor (Pgr)] with sets of steroid target genes that were identified in single brain regions. These coexpression relationships were also present in distinct other brain regions, suggestive of as yet unidentified coordinate regulation of brain regions by, for example, glucocorticoids and estrogens. Second, coexpression of a set of 62 known NR coregulators and the six steroid receptors in 12 nonoverlapping mouse brain regions revealed selective downstream pathways, such as Pak6 as a mediator for the effects of Ar and Gr on dopaminergic transmission. Third, Magel2 and Irs4 were identified and validated as strongly responsive targets to the estrogen diethylstilbestrol in the mouse hypothalamus. The brain- and genome-wide correlations of mRNA expression levels of six steroid receptors that we provide constitute a rich resource for further predictions and understanding of brain modulation by steroid hormones. PMID:26811448

  1. DNA enrichment approaches to identify unauthorized genetically modified organisms (GMOs).

    Science.gov (United States)

    Arulandhu, Alfred J; van Dijk, Jeroen P; Dobnik, David; Holst-Jensen, Arne; Shi, Jianxin; Zel, Jana; Kok, Esther J

    2016-07-01

    With the increased global production of different genetically modified (GM) plant varieties, chances increase that unauthorized GM organisms (UGMOs) may enter the food chain. At the same time, the detection of UGMOs is a challenging task because of the limited sequence information that will generally be available. PCR-based methods are available to detect and quantify known UGMOs in specific cases. If this approach is not feasible, DNA enrichment of the unknown adjacent sequences of known GMO elements is one way to detect the presence of UGMOs in a food or feed product. These enrichment approaches are also known as chromosome walking or gene walking (GW). In recent years, enrichment approaches have been coupled with next generation sequencing (NGS) analysis and implemented in, amongst others, the medical and microbiological fields. The present review will provide an overview of these approaches and an evaluation of their applicability in the identification of UGMOs in complex food or feed samples. PMID:27086015

  2. DNA enrichment approaches to identify unauthorized genetically modified organisms (GMOs).

    Science.gov (United States)

    Arulandhu, Alfred J; van Dijk, Jeroen P; Dobnik, David; Holst-Jensen, Arne; Shi, Jianxin; Zel, Jana; Kok, Esther J

    2016-07-01

    With the increased global production of different genetically modified (GM) plant varieties, chances increase that unauthorized GM organisms (UGMOs) may enter the food chain. At the same time, the detection of UGMOs is a challenging task because of the limited sequence information that will generally be available. PCR-based methods are available to detect and quantify known UGMOs in specific cases. If this approach is not feasible, DNA enrichment of the unknown adjacent sequences of known GMO elements is one way to detect the presence of UGMOs in a food or feed product. These enrichment approaches are also known as chromosome walking or gene walking (GW). In recent years, enrichment approaches have been coupled with next generation sequencing (NGS) analysis and implemented in, amongst others, the medical and microbiological fields. The present review will provide an overview of these approaches and an evaluation of their applicability in the identification of UGMOs in complex food or feed samples.

  3. Contemporary Approaches for Identifying Rare Bone Disease Causing Genes

    OpenAIRE

    Farber, Charles R; Clemens, Thomas L.

    2013-01-01

    Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisticated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. ...

  4. A Cooperative Reinforcement Learning Approach for Inter-Cell Interference Coordination in OFDMA Cellular Networks

    OpenAIRE

    Dirani, Mariana; Altman, Zwi

    2010-01-01

    Interference Management International audience Inter-Cell Interference Coordination (ICIC) is commonly identified as a key radio resource management mechanism to enhance system performance of 4G networks. This paper addresses the problem of ICIC in the downlink of cellular OFDMA (LTE and WiMAX) systems in the context of Self-Organizing Networks (SON). The problem is posed as a cooperative Multi-Agent control problem. Each base station is an agent that dynamically changes power masks on ...

  5. Identifying Predictors of Physics Item Difficulty: A Linear Regression Approach

    Science.gov (United States)

    Mesic, Vanes; Muratovic, Hasnija

    2011-01-01

    Large-scale assessments of student achievement in physics are often approached with an intention to discriminate students based on the attained level of their physics competencies. Therefore, for purposes of test design, it is important that items display an acceptable discriminatory behavior. To that end, it is recommended to avoid extraordinary…

  6. Identifying the "Truly Disadvantaged": A Comprehensive Biosocial Approach

    Science.gov (United States)

    Barnes, J. C.; Beaver, Kevin M.; Connolly, Eric J.; Schwartz, Joseph A.

    2016-01-01

    There has been significant interest in examining the developmental factors that predispose individuals to chronic criminal offending. This body of research has identified some social-environmental risk factors as potentially important. At the same time, the research producing these results has generally failed to employ genetically sensitive…

  7. Identifying predictors of physics item difficulty: A linear regression approach

    OpenAIRE

    Hasnija Muratovic; Vanes Mesic

    2011-01-01

    Large-scale assessments of student achievement in physics are often approached with an intention to discriminate students based on the attained level of their physics competencies. Therefore, for purposes of test design, it is important that items display an acceptable discriminatory behavior. To that end, it is recommended to avoid extraordinary difficult and very easy items. Knowing the factors that influence physics item difficulty makes it possible to model the item difficulty even before...

  8. The flux-coordinate independent approach applied to X-point geometries

    International Nuclear Information System (INIS)

    A Flux-Coordinate Independent (FCI) approach for anisotropic systems, not based on magnetic flux coordinates, has been introduced in Hariri and Ottaviani [Comput. Phys. Commun. 184, 2419 (2013)]. In this paper, we show that the approach can tackle magnetic configurations including X-points. Using the code FENICIA, an equilibrium with a magnetic island has been used to show the robustness of the FCI approach to cases in which a magnetic separatrix is present in the system, either by design or as a consequence of instabilities. Numerical results are in good agreement with the analytic solutions of the sound-wave propagation problem. Conservation properties are verified. Finally, the critical gain of the FCI approach in situations including the magnetic separatrix with an X-point is demonstrated by a fast convergence of the code with the numerical resolution in the direction of symmetry. The results highlighted in this paper show that the FCI approach can efficiently deal with X-point geometries

  9. Computational approaches to identify functional genetic variants in cancer genomes

    Science.gov (United States)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris; Ritchie, Graham R.S.; Creixell, Pau; Karchin, Rachel; Vazquez, Miguel; Fink, J. Lynn; Kassahn, Karin S.; Pearson, John V.; Bader, Gary; Boutros, Paul C.; Muthuswamy, Lakshmi; Ouellette, B.F. Francis; Reimand, Jüri; Linding, Rune; Shibata, Tatsuhiro; Valencia, Alfonso; Butler, Adam; Dronov, Serge; Flicek, Paul; Shannon, Nick B.; Carter, Hannah; Ding, Li; Sander, Chris; Stuart, Josh M.; Stein, Lincoln D.; Lopez-Bigas, Nuria

    2014-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor, but only a minority drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype. PMID:23900255

  10. A Bayesian Approach to Identifying New Risk Factors for Dementia

    OpenAIRE

    Wen, Yen-Hsia; Wu, Shihn-Sheng; Lin, Chun-Hung Richard; Tsai, Jui-Hsiu; Yang, Pinchen; Chang, Yang-Pei; Tseng, Kuan-Hua

    2016-01-01

    Abstract Dementia is one of the most disabling and burdensome health conditions worldwide. In this study, we identified new potential risk factors for dementia from nationwide longitudinal population-based data by using Bayesian statistics. We first tested the consistency of the results obtained using Bayesian statistics with those obtained using classical frequentist probability for 4 recognized risk factors for dementia, namely severe head injury, depression, diabetes mellitus, and vascular...

  11. Multidisciplinary approach to identify aquifer-peatland connectivity

    Science.gov (United States)

    Larocque, Marie; Pellerin, Stéphanie; Cloutier, Vincent; Ferlatte, Miryane; Munger, Julie; Quillet, Anne; Paniconi, Claudio

    2015-04-01

    In southern Quebec (Canada), wetlands sustain increasing pressures from agriculture, urban development, and peat exploitation. To protect both groundwater and ecosystems, it is important to be able to identify how, where, and to what extent shallow aquifers and wetlands are connected. This study focuses on peatlands which are especially abundant in Quebec. The objective of this research was to better understand aquifer-peatland connectivity and to identify easily measured indicators of this connectivity. Geomorphology, hydrogeochemistry, and vegetation were selected as key indicators of connectivity. Twelve peatland transects were instrumented and monitored in the Abitibi (slope peatlands associated with eskers) and Centre-du-Quebec (depression peatlands) regions of Quebec (Canada). Geomorphology, geology, water levels, water chemistry, and vegetation species were identified/measured on all transects. Flow conditions were simulated numerically on two typical transects. Results show that a majority of peatland transects receives groundwater from a shallow aquifer. In slope peatlands, groundwater flows through the organic deposits towards the peatland center. In depression peatlands, groundwater flows only 100-200 m within the peatland before being redirected through surface routes towards the outlet. Flow modeling and sensitivity analysis have identified that the thickness and hydraulic conductivity of permeable deposits close to the peatland and beneath the organic deposits influence flow directions within the peatland. Geochemical data have confirmed the usefulness of total dissolved solids (TDS) exceeding 14 mg/L as an indicator of the presence of groundwater within the peatland. Vegetation surveys have allowed the identification of species and groups of species that occur mostly when groundwater is present, for instance Carex limosa and Sphagnum russowii. Geomorphological conditions (slope or depression peatland), TDS, and vegetation can be measured

  12. Bioinformatics approaches for identifying new therapeutic bioactive peptides in food

    OpenAIRE

    Nora Khaldi

    2012-01-01

    ABSTRACT:The traditional methods for mining foods for bioactive peptides are tedious and long. Similar to the drug industry, the length of time to identify and deliver a commercial health ingredient that reduces disease symptoms can take anything between 5 to 10 years. Reducing this time and effort is crucial in order to create new commercially viable products with clear and important health benefits. In the past few years, bioinformatics, the science that brings together fast computational b...

  13. Computational approaches to identify functional genetic variants in cancer genomes

    DEFF Research Database (Denmark)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris;

    2013-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu...... of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....

  14. A Maximum Entropy Approach to Identifying Sentence Boundaries

    CERN Document Server

    Reynar, J C; Reynar, Jeffrey C.; Ratnaparkhi, Adwait

    1997-01-01

    We present a trainable model for identifying sentence boundaries in raw text. Given a corpus annotated with sentence boundaries, our model learns to classify each occurrence of ., ?, and ! as either a valid or invalid sentence boundary. The training procedure requires no hand-crafted rules, lexica, part-of-speech tags, or domain-specific information. The model can therefore be trained easily on any genre of English, and should be trainable on any other Roman-alphabet language. Performance is comparable to or better than the performance of similar systems, but we emphasize the simplicity of retraining for new domains.

  15. A Coordinated Approach to Channel Estimation in Large-scale Multiple-antenna Systems

    CERN Document Server

    Yin, Haifan; Filippou, Miltiades; Liu, Yingzhuang

    2012-01-01

    This paper addresses the problem of channel estimation in multi-cell interference-limited cellular networks. We consider systems employing multiple antennas and are interested in both the finite and large-scale antenna number regimes (so-called "Massive MIMO"). Such systems deal with the multi-cell interference by way of per-cell beamforming applied at each base station. Channel estimation in such networks, which is known to be hampered by the pilot contamination effect, constitute a major bottleneck for overall performance. We present a novel approach which tackles this problem by enabling a low-rate coordination between cells during the channel estimation phase itself. The coordination makes use of the additional second-order statistical information about the user channels, which are shown to offer a powerful way of discriminating across interfering users with even strongly correlated pilot sequences. Importantly, we demonstrate analytically that in the large number of antennas regime the pilot contaminatio...

  16. Semi-analytical approach for the Vaidya metric in double-null coordinates

    CERN Document Server

    Girotto, F; Girotto, Fernando; Saa, Alberto

    2004-01-01

    We reexamine here a problem considered in detail before by Waugh and Lake: the solutions of spherically symmetric Einstein's equations with a radial flow of unpolarized radiation (the Vaidya metric) in double-null coordinates. This problem is known to be not analytically solvable, the only known explicit solutions correspond to the constant mass case (Schwarzschild solution in Kruskal-Szekeres form) and the linear and exponential mass functions originally discovered by Waugh and Lake. We present here a semi-analytical approach that can be used to discuss some qualitative and quantitative aspects of the Vaidya metric in double-null coordinates for generic mass functions. We present also a new analytical solution corresponding to $(1/v)$-mass function.

  17. Illustration and analysis of a coordinated approach to an effective forensic trace evidence capability.

    Science.gov (United States)

    Stoney, David A; Stoney, Paul L

    2015-08-01

    An effective trace evidence capability is defined as one that exploits all useful particle types, chooses appropriate technologies to do so, and directly integrates the findings with case-specific problems. Limitations of current approaches inhibit the attainment of an effective capability and it has been strongly argued that a new approach to trace evidence analysis is essential. A hypothetical case example is presented to illustrate and analyze how forensic particle analysis can be used as a powerful practical tool in forensic investigations. The specifics in this example, including the casework investigation, laboratory analyses, and close professional interactions, provide focal points for subsequent analysis of how this outcome can be achieved. This leads to the specification of five key elements that are deemed necessary and sufficient for effective forensic particle analysis: (1) a dynamic forensic analytical approach, (2) concise and efficient protocols addressing particle combinations, (3) multidisciplinary capabilities of analysis and interpretation, (4) readily accessible external specialist resources, and (5) information integration and communication. A coordinating role, absent in current approaches to trace evidence analysis, is essential to achieving these elements. However, the level of expertise required for the coordinating role is readily attainable. Some additional laboratory protocols are also essential. However, none of these has greater staffing requirements than those routinely met by existing forensic trace evidence practitioners. The major challenges that remain are organizational acceptance, planning and implementation.

  18. Identifying Pathogenicity Islands in Bacterial Pathogenomics Using Computational Approaches

    Directory of Open Access Journals (Sweden)

    Dongsheng Che

    2014-01-01

    Full Text Available High-throughput sequencing technologies have made it possible to study bacteria through analyzing their genome sequences. For instance, comparative genome sequence analyses can reveal the phenomenon such as gene loss, gene gain, or gene exchange in a genome. By analyzing pathogenic bacterial genomes, we can discover that pathogenic genomic regions in many pathogenic bacteria are horizontally transferred from other bacteria, and these regions are also known as pathogenicity islands (PAIs. PAIs have some detectable properties, such as having different genomic signatures than the rest of the host genomes, and containing mobility genes so that they can be integrated into the host genome. In this review, we will discuss various pathogenicity island-associated features and current computational approaches for the identification of PAIs. Existing pathogenicity island databases and related computational resources will also be discussed, so that researchers may find it to be useful for the studies of bacterial evolution and pathogenicity mechanisms.

  19. PROCESS OF IDENTIFYING COMPETENCIES BASED ON A FUNCTIONAL APPROACH

    Directory of Open Access Journals (Sweden)

    NAOUFAL SEFIANI

    2012-01-01

    Full Text Available To cope with fast change of the technological and organizational context, managers need tools to help them to improve competence management. Our contribution aims at supporting the task of competence identification that is considered as the first step of the management process. The proposed identification involves tree stages.The first stage concerns the research of competences based on a functional approach. The second stage is to define a typology of the component of competence (characterization and the third stage to define the core competencies of competence (prioritization. The application of the method in an industrial case in the logisticsfield confirms the possibility of using the “principle of solution” to provide a dynamic process for the identification of requisite competencies.

  20. A Novel Approach for Identify Small and Capital Handwritten Letter

    Directory of Open Access Journals (Sweden)

    Ekta Tiwari

    2012-06-01

    Full Text Available A handwritten character is represented as a sequence of strokes whose features are extracted and classified. Although the off-line and on-line character recognition techniques have different approaches, they share a lot of common problems and solutions. The printed documents available in the form of books, papers, magazines, etc. are scanned using standard scanners which produce an image of the scanned document. The preprocessed image is segmented using an algorithm which decomposes the scanned text into paragraphs using special space detection technique and then the paragraphs into lines using vertical histograms, and lines into words using horizontal histograms, and words into character image glyphs using horizontal histograms. Each image glyph is comprised of 24x24 pixels. Thus a database of character image glyphs is created out of the segmentation phase. The various features that are considered for classification are the character height, character width, the number of horizontal lines (long and short, image centroid and special dots. we proposed extracted features were passed to a Support Vector Machine (SVM where the characters are classified by Supervised Learning Algorithm. These classes are mapped onto for recognition. Then the text is reconstructed using fonts.

  1. Bioinformatics approaches for identifying new therapeutic bioactive peptides in food

    Directory of Open Access Journals (Sweden)

    Nora Khaldi

    2012-10-01

    Full Text Available ABSTRACT:The traditional methods for mining foods for bioactive peptides are tedious and long. Similar to the drug industry, the length of time to identify and deliver a commercial health ingredient that reduces disease symptoms can take anything between 5 to 10 years. Reducing this time and effort is crucial in order to create new commercially viable products with clear and important health benefits. In the past few years, bioinformatics, the science that brings together fast computational biology, and efficient genome mining, is appearing as the long awaited solution to this problem. By quickly mining food genomes for characteristics of certain food therapeutic ingredients, researchers can potentially find new ones in a matter of a few weeks. Yet, surprisingly, very little success has been achieved so far using bioinformatics in mining for food bioactives.The absence of food specific bioinformatic mining tools, the slow integration of both experimental mining and bioinformatics, and the important difference between different experimental platforms are some of the reasons for the slow progress of bioinformatics in the field of functional food and more specifically in bioactive peptide discovery.In this paper I discuss some methods that could be easily translated, using a rational peptide bioinformatics design, to food bioactive peptide mining. I highlight the need for an integrated food peptide database. I also discuss how to better integrate experimental work with bioinformatics in order to improve the mining of food for bioactive peptides, therefore achieving a higher success rates.

  2. Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

    Science.gov (United States)

    Marone, Palma Ann; Birkenbach, Victoria L; Hayes, A Wallace

    2016-01-01

    Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products. PMID:26657815

  3. Enhanced Approaches for Identifying Amadori Products: Application to Peanut Allergens.

    Science.gov (United States)

    Johnson, Katina L; Williams, Jason G; Maleki, Soheila J; Hurlburt, Barry K; London, Robert E; Mueller, Geoffrey A

    2016-02-17

    The dry roasting of peanuts is suggested to influence allergic sensitization as a result of the formation of advanced glycation end products (AGEs) on peanut proteins. Identifying AGEs is technically challenging. The AGEs of a peanut allergen were probed with nano-scale liquid chromatography-electrospray ionization-mass spectrometry (nanoLC-ESI-MS) and tandem mass spectrometry (MS/MS) analyses. Amadori product ions matched to expected peptides and yielded fragments that included a loss of three waters and HCHO. As a result of the paucity of b and y ions in the MS/MS spectrum, standard search algorithms do not perform well. Reactions with isotopically labeled sugars confirmed that the peptides contained Amadori products. An algorithm was developed on the basis of information content (Shannon entropy) and the loss of water and HCHO. Results with test data show that the algorithm finds the correct spectra with high precision, reducing the time needed to manually inspect data. Computational and technical improvements allowed for better identification of the chemical differences between modified and unmodified proteins. PMID:26811263

  4. A generic approach to identifying faults in HVAC plants

    Energy Technology Data Exchange (ETDEWEB)

    Dexter, A.L.; Benouarets, M. [Univ. of Oxford (United Kingdom). Dept. of Engineering Science

    1996-11-01

    The paper describes a semi-qualitative model-based method of fault diagnosis that is suitable for generic applications over a range of different sizes and designs of heating, ventilating, and air-conditioning (HVAC) plant items, such as terminal boxes and heating coils. The method requires no training data from the actual plant and is suitable for real-time implementation in packaged digital controllers or in the outstations of energy management and control systems. The scheme uses reference models describing fault free and faulty operation that are generated from data produced by simulating a number of plants of the same type as the plant under test. The method of diagnosis takes account of the ambiguity introduced by using such generic reference models that can arise if the symptoms of correct and faulty operation, or of different faults, are similar at certain operating points. The results presented demonstrate that the scheme can successfully detect and identify faults in the cooling coil subsystem of an air-handling unit.

  5. A landscape ecology approach identifies important drivers of urban biodiversity.

    Science.gov (United States)

    Turrini, Tabea; Knop, Eva

    2015-04-01

    Cities are growing rapidly worldwide, yet a mechanistic understanding of the impact of urbanization on biodiversity is lacking. We assessed the impact of urbanization on arthropod diversity (species richness and evenness) and abundance in a study of six cities and nearby intensively managed agricultural areas. Within the urban ecosystem, we disentangled the relative importance of two key landscape factors affecting biodiversity, namely the amount of vegetated area and patch isolation. To do so, we a priori selected sites that independently varied in the amount of vegetated area in the surrounding landscape at the 500-m scale and patch isolation at the 100-m scale, and we hold local patch characteristics constant. As indicator groups, we used bugs, beetles, leafhoppers, and spiders. Compared to intensively managed agricultural ecosystems, urban ecosystems supported a higher abundance of most indicator groups, a higher number of bug species, and a lower evenness of bug and beetle species. Within cities, a high amount of vegetated area increased species richness and abundance of most arthropod groups, whereas evenness showed no clear pattern. Patch isolation played only a limited role in urban ecosystems, which contrasts findings from agro-ecological studies. Our results show that urban areas can harbor a similar arthropod diversity and abundance compared to intensively managed agricultural ecosystems. Further, negative consequences of urbanization on arthropod diversity can be mitigated by providing sufficient vegetated space in the urban area, while patch connectivity is less important in an urban context. This highlights the need for applying a landscape ecological approach to understand the mechanisms shaping urban biodiversity and underlines the potential of appropriate urban planning for mitigating biodiversity loss.

  6. A Bayesian Approach to Identifying New Risk Factors for Dementia

    Science.gov (United States)

    Wen, Yen-Hsia; Wu, Shihn-Sheng; Lin, Chun-Hung Richard; Tsai, Jui-Hsiu; Yang, Pinchen; Chang, Yang-Pei; Tseng, Kuan-Hua

    2016-01-01

    Abstract Dementia is one of the most disabling and burdensome health conditions worldwide. In this study, we identified new potential risk factors for dementia from nationwide longitudinal population-based data by using Bayesian statistics. We first tested the consistency of the results obtained using Bayesian statistics with those obtained using classical frequentist probability for 4 recognized risk factors for dementia, namely severe head injury, depression, diabetes mellitus, and vascular diseases. Then, we used Bayesian statistics to verify 2 new potential risk factors for dementia, namely hearing loss and senile cataract, determined from the Taiwan's National Health Insurance Research Database. We included a total of 6546 (6.0%) patients diagnosed with dementia. We observed older age, female sex, and lower income as independent risk factors for dementia. Moreover, we verified the 4 recognized risk factors for dementia in the older Taiwanese population; their odds ratios (ORs) ranged from 3.469 to 1.207. Furthermore, we observed that hearing loss (OR = 1.577) and senile cataract (OR = 1.549) were associated with an increased risk of dementia. We found that the results obtained using Bayesian statistics for assessing risk factors for dementia, such as head injury, depression, DM, and vascular diseases, were consistent with those obtained using classical frequentist probability. Moreover, hearing loss and senile cataract were found to be potential risk factors for dementia in the older Taiwanese population. Bayesian statistics could help clinicians explore other potential risk factors for dementia and for developing appropriate treatment strategies for these patients. PMID:27227925

  7. Genetic Approaches To Identifying Novel Osteoporosis Drug Targets.

    Science.gov (United States)

    Brommage, Robert

    2015-10-01

    During the past two decades effective drugs for treating osteoporosis have been developed, including anti-resorptives inhibiting bone resorption (estrogens, the SERM raloxifene, four bisphosphonates, RANKL inhibitor denosumab) and the anabolic bone forming daily injectable peptide teriparatide. Two potential drugs (odanacatib and romosozumab) are in late stage clinical development. The most pressing unmet need is for orally active anabolic drugs. This review describes the basic biological studies involved in developing these drugs, including the animal models employed for osteoporosis drug development. The genomics revolution continues to identify potential novel osteoporosis drug targets. Studies include human GWAS studies and identification of mutant genes in subjects having abnormal bone mass, mouse QTL and gene knockouts, and gene expression studies. Multiple lines of evidence indicate that Wnt signaling plays a major role in regulating bone formation and continued study of this complex pathway is likely to lead to key discoveries. In addition to the classic Wnt signaling targets DKK1 and sclerostin, LRP4, LRP5/LRP6, SFRP4, WNT16, and NOTUM can potentially be targeted to modulate Wnt signaling. Next-generation whole genome and exome sequencing, RNA-sequencing and CRISPR/CAS9 gene editing are new experimental techniques contributing to understanding the genome. The International Knockout Mouse Consortium efforts to knockout and phenotype all mouse genes are poised to accelerate. Accumulating knowledge will focus attention on readily accessible databases (Big Data). Efforts are underway by the International Bone and Mineral Society to develop an annotated Skeletome database providing information on all genes directly influencing bone mass, architecture, mineralization or strength. PMID:25833316

  8. A Staged Approach for Identifying Children with Developmental Coordination Disorder from the Population

    Science.gov (United States)

    Missiuna, Cheryl; Cairney, John; Pollock, Nancy; Russell, Dianne; Macdonald, Kathryn; Cousins, Martha; Veldhuizen, Scott; Schmidt, Louis

    2011-01-01

    The purpose of this study was to describe the motor, attention and intellectual characteristics of a population-based sample of children first screened for motor impairment and to discuss the recruitment and identification methods employed. A two stage cross-sectional, school-based survey was conducted to screen for children with motor…

  9. New approach for motion coordination of a mobile manipulator using fuzzy behavioral algorithms

    Science.gov (United States)

    Haeusler, Kurt; Klement, Erich P.; Zeichen, Gerfried

    1998-10-01

    In this paper a new approach for the coordination of the motion axes of a mobile manipulator based on fuzzy behavioral algorithms and its implementation on a physical demonstrator is presented. The kinematic redundancy of the overall system (consisting of a 7 DOF manipulator and a 3 DOF mobile robot) will be used for autonomous and reactive motion of the mobile manipulator within poorly structured and even dynamically changing surroundings. Sensors around the mobile and along the manipulator will provide the necessary information for navigation purposes and perception of the environment.

  10. Coordination Devices in the Refurbishment Design Process: A Partial-Correlation Approach

    Directory of Open Access Journals (Sweden)

    Azlan Shah Ali

    2009-12-01

    Full Text Available Building refurbishment is an important sector in the Malaysian construction industry. The increase the number of building renovations, alterations, extensions and extensive repair works contributed to the high demand for refurbishment projects. However, refurbishment projects are more difficult to manage compared to new-built, due to uncertainty factors inherent in the projects. Therefore, this paper identifies factors that contributed to uncertainty and shows how it affects design performance of refurbishment projects. This paper was also extended to the used of coordination devices to improve design performance from the effect of uncertainty in the projects. Partial-correlation technique was used in data analysis to check any significant moderate effects of coordination devices to control the negative effect of uncertainty on design performance of refurbishment projects. Four (4 coordination devices involved in the partial-correlation tests. The results concluded that the use of lateral relations and architect’s characteristics are most likely reducing the uncertainty of client attributes towards design completeness before work started on site.

  11. COORDINATION IN MULTILEVEL NETWORK-CENTRIC CONTROL SYSTEMS OF REGIONAL SECURITY: APPROACH AND FORMAL MODEL

    Directory of Open Access Journals (Sweden)

    A. V. Masloboev

    2015-01-01

    Full Text Available The paper deals with development of methods and tools for mathematical and computer modeling of the multilevel network-centric control systems of regional security. This research is carried out under development strategy implementation of the Arctic zone of the Russian Federation and national safeguarding for the period before 2020 in the Murmansk region territory. Creation of unified interdepartmental multilevel computer-aided system is proposed intended for decision-making information support and socio-economic security monitoring of the Arctic regions of Russia. The distinctive features of the investigated system class are openness, self-organization, decentralization of management functions and decision-making, weak hierarchy in the decision-making circuit and goal generation capability inside itself. Research techniques include functional-target approach, mathematical apparatus of multilevel hierarchical system theory and principles of network-centric control of distributed systems with pro-active components and variable structure. The work considers network-centric management local decisions coordination problem-solving within the multilevel distributed systems intended for information support of regional security. The coordination problem-solving approach and problem formalization in the multilevel network-centric control systems of regional security have been proposed based on developed multilevel recurrent hierarchical model of regional socio-economic system complex security. The model provides coordination of regional security indexes, optimized by the different elements of multilevel control systems, subject to decentralized decision-making. The model specificity consists in application of functional-target technology and mathematical apparatus of multilevel hierarchical system theory for coordination procedures implementation of the network-centric management local decisions. The work-out and research results can find further

  12. Case Studies on an Approach to Multiple Autonomous Vehicle Motion Coordination

    Institute of Scientific and Technical Information of China (English)

    D.K. Liu; X. Wu; G. Paul; G. Dissanayake

    2006-01-01

    This paper conducts a series of case studies on a novel Simultaneous Path and Motion Planning (SiPaMoP) approach[1] to multiple autonomous or Automated Guided Vehicle (AGV) motion coordination in bidirectional networks. The SiPaMoP approach plans collision-free paths for vehicles based on the principle of shortest path by dynamically changing the vehicles' paths, traveling speeds or waiting times, whichever gives the shortest traveling time. It integrates path planning, collision avoidance and motion planning into a comprehensive model and optimizes the vehicles' path and motion to minimize the completion time of a set of tasks. Five case studies, i.e., head-on collision avoidance,catching-up collision avoidance, buffer node generation and collision avoidance, prioritybased motion coordination, and safety distance based planning, are presented. The results demonstrated that the method can effectively plan the path and motion for a team of autonomous vehicles or AGVs, and solve the problems of traffic congestion and collision under various conditions.

  13. A new approach on restoration of dynamic measurement uncertainties in optical precision coordinate metrology

    International Nuclear Information System (INIS)

    This paper presents a new approach to the restoration of dynamic influenced measurement uncertainties in optical precision coordinate metrology (OPCM) using image sensors to measure geometrical features. Dynamic measurements within the context of this paper are based upon relative motion between the imaging setup (CCD-camera and optical system) and the measuring object respectively the measuring scene. The dynamic image acquisition causes image motion blur effects, which downgrades the uncertainties of the measurand. The approach presented deals with a new technique to restore motion degraded images using different methods to analyze important image features by extending the famous state of the art Richardson-Lucy image restoration technique using a new convergence criteria based on the variation of the detectable sub-pixel edge position of each iteration

  14. A new neural net approach to robot 3D perception and visuo-motor coordination

    Science.gov (United States)

    Lee, Sukhan

    1992-01-01

    A novel neural network approach to robot hand-eye coordination is presented. The approach provides a true sense of visual error servoing, redundant arm configuration control for collision avoidance, and invariant visuo-motor learning under gazing control. A 3-D perception network is introduced to represent the robot internal 3-D metric space in which visual error servoing and arm configuration control are performed. The arm kinematic network performs the bidirectional association between 3-D space arm configurations and joint angles, and enforces the legitimate arm configurations. The arm kinematic net is structured by a radial-based competitive and cooperative network with hierarchical self-organizing learning. The main goal of the present work is to demonstrate that the neural net representation of the robot 3-D perception net serves as an important intermediate functional block connecting robot eyes and arms.

  15. Low dose radiation effects: an integrative european approach (Risc-Rad Project) coordinated by the Cea

    International Nuclear Information System (INIS)

    RISC-RAD (Radiosensitivity of Individuals and Susceptibility to Cancer induced by ionizing Radiations) is an Integrated Project funded by the European Commission under 6. Framework Programme / EURATOM. RISC-RAD started on 1. January 2004 for a duration of four years. Coordinated by Cea (Dr Laure Sabatier), it involves 11 European countries (Austria, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Spain, Sweden and the United Kingdom) and 29 research institutions. Objectives: Exposures to low and protracted doses of ionizing radiation are very frequent in normal living environment, at work places, in industry and in medicine. Effects of these exposures on human health cannot be reliably assessed by epidemiological methods, nor is thoroughly understood by biologists. RISC-RAD project proposes to help bridging the gap of scientific knowledge about these effects. To achieve this goal, a necessary key step is to understand the basic mechanisms by which radiation induces cancer. Studying this multistage process in an integrated way, the project offers a new biological approach characterised by and clear-cut and objective-driven scientific policy: the project is focused on the effects of low doses (less than 100 mSv) and protracted doses of radiation. It aims at identifying new parameters that take into account the differences in radiation responses between individuals. A group of modelers works closely with the experimental teams in order to better quantify the risks associated with low and protracted doses. Research work is divided into five work packages interacting closely with each other. WP1 is dedicated to DNA damage. Ionizing Radiation (IR) produce a broad spectrum of base modifications and DNA strand breaks of different kinds, among which double-strand breaks and 'clustered damage' which is thought to be a major feature in biological effectiveness of IR. The aim of Work Package 1 is to improve understanding of the initial DNA damage induced by

  16. Approach to valuing visual pollution from Western Electricity Production. [For Western Systems Coordinating Council area

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, L.E.

    1977-02-01

    This paper outlines an approach to valuing visual pollution from electric power plants. The differences between public-good pollution externalities, such as these aesthetic damages, and other market failures are discussed. Approaches generally used to value externalities are briefly described. The approach used relies heavily on an earlier application of bidding games to estimate people's willingness to pay for abatement of emissions from the Four Corners fossil-fuel power plant in northwestern New Mexico. The results of these surveys were used here to estimate the value of visual pollution from electric power plants for residents of and visitors to the Four Corners Air Quality Control Region, as a function of power plant emissions in that region. The approach presented here for the Four Corners region is structured so that replication for other air quality control regions is relatively easy. Preliminary results of this procedure for all of the air quality control regions in the Western Systems Coordinating Council area are presented. Visual pollution damages from electric power plants to residents of and recreational visitors to these western regions are estimated to total more than $100 million annually by 1985. These damages are expected to occur unless additional pollution controls are implemented, even if these subject populations do not increase.

  17. Hermitian spin-orbit Hamiltonians on a surface in orthogonal curvilinear coordinates: A new practical approach

    Science.gov (United States)

    Shikakhwa, M. S.; Chair, N.

    2016-05-01

    The Hermitian Hamiltonian of a spin one-half particle with spin-orbit coupling (SOC) confined to a surface that is embedded in a three-dimensional space spanned by a general Orthogonal Curvilinear Coordinate (OCC) is constructed. A gauge field formalism, where the SOC is expressed as a non-Abelian SU (2) gauge field is used. A new practical approach, based on the physical argument that upon confining the particle to the surface by a potential, then it is the physical Hermitian momentum operator transverse to the surface, rather than just the derivative with respect to the transverse coordinate that should be dropped from the Hamiltonian. Doing so, it is shown that the Hermitian Hamiltonian for SOC is obtained with the geometric potential and the geometric kinetic energy terms emerging naturally. The geometric potential is shown to represent a coupling between the transverse component of the gauge field and the mean curvature of the surface that replaces the coupling between the transverse momentum and the gauge field. The most general Hermitian Hamiltonian with linear SOC on a general surface embedded in any 3D OCC system is reported. Explicit plug-and-play formulae for this Hamiltonian on the surfaces of a cylinder, a sphere and a torus are given. The formalism is applied to the Rashba SOC in three dimensions (3D RSOC) and the explicit expressions for the surface Hamiltonians on these three geometries are worked out.

  18. A combinatorial bidirectional and bicistronic approach for coordinated multi-gene expression in corn.

    Science.gov (United States)

    Kumar, Sandeep; AlAbed, Diaa; Whitteck, John T; Chen, Wei; Bennett, Sara; Asberry, Andrew; Wang, Xiujuan; DeSloover, Daniel; Rangasamy, Murugesan; Wright, Terry R; Gupta, Manju

    2015-03-01

    Transgene stacking in trait development process through genetic engineering is becoming complex with increased number of desired traits and multiple modes of action for each trait. We demonstrate here a novel gene stacking strategy by combining bidirectional promoter (BDP) and bicistronic approaches to drive coordinated expression of multi-genes in corn. A unidirectional promoter, Ubiquitin-1 (ZMUbi1), from Zea mays was first converted into a synthetic BDP, such that a single promoter can direct the expression of two genes from each end of the promoter. The BDP system was then combined with a bicistronic organization of genes at both ends of the promoter by using a Thosea asigna virus 2A auto-cleaving domain. With this gene stacking configuration, we have successfully obtained expression in transgenic corn of four transgenes; three transgenes conferring insect (cry34Ab1 and cry35Ab1) and herbicide (aad1) resistance, and a phiyfp reporter gene using a single ZMUbi1 bidirectional promoter. Gene expression analyses of transgenic corn plants confirmed better coordinated expression of the four genes compared to constructs driving each gene by independent unidirectional ZmUbi1 promoter. To our knowledge, this is the first report that demonstrates application of a single promoter for co-regulation of multiple genes in a crop plant. This stacking technology would be useful for engineering metabolic pathways both for basic and applied research. PMID:25657118

  19. Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

    DEFF Research Database (Denmark)

    Liu, Y.; Melillo, J.; Niu, S.;

    2011-01-01

    Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation...... a coordinated approach that combines long-term, large-scale global change experiments with process studies and modeling. Long-term global change manipulative experiments, especially in high-priority ecosystems such as tropical forests and high-latitude regions, are essential to maximize information gain...... concerning future states of the earth system. The long-term experiments should be conducted in tandem with complementary process studies, such as those using model ecosystems, species replacements, laboratory incubations, isotope tracers, and greenhouse facilities. Models are essential to assimilate data...

  20. Control of molecular rotor rotational frequencies in porous coordination polymers using a solid-solution approach.

    Science.gov (United States)

    Inukai, Munehiro; Fukushima, Tomohiro; Hijikata, Yuh; Ogiwara, Naoki; Horike, Satoshi; Kitagawa, Susumu

    2015-09-30

    Rational design to control the dynamics of molecular rotors in crystalline solids is of interest because it offers advanced materials with precisely tuned functionality. Herein, we describe the control of the rotational frequency of rotors in flexible porous coordination polymers (PCPs) using a solid-solution approach. Solid-solutions of the flexible PCPs [{Zn(5-nitroisophthalate)x(5-methoxyisophthalate)1-x(deuterated 4,4'-bipyridyl)}(DMF·MeOH)]n allow continuous modulation of cell volume by changing the solid-solution ratio x. Variation of the isostructures provides continuous changes in the local environment around the molecular rotors (pyridyl rings of the 4,4'-bipyridyl group), leading to the control of the rotational frequency without the need to vary the temperature. PMID:26368067

  1. Gene-based Association Approach Identify Genes Across Stress Traits in Fruit Flies

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Edwards, Stefan McKinnon; Sarup, Pernille Merete;

    approach grouping variants accordingly to gene position, thus lowering the number of statistical tests performed and increasing the probability of identifying genes with small to moderate effects. Using this approach we identify numerous genes associated with different types of stresses in Drosophila...

  2. Lifting the burden: a coordinated approach to action on Aboriginal tobacco resistance and control in NSW.

    Science.gov (United States)

    Sarin, Jasmine; Hunt, Jennifer; Ivers, Rowena; Smyth, Colleen

    2015-01-01

    Smoking prevalence continues to be significantly higher among Aboriginal people than non-Aboriginal people, resulting in a range of serious health consequences and inequities. The Aboriginal Health and Medical Research Council of New South Wales (AHandMRC) and the New South Wales (NSW) Ministry of Health (the Ministry) have worked in partnership to develop The ATRAC Framework: A Strategic Framework for Aboriginal Tobacco Resistance and Control in NSW, in collaboration with Aboriginal communities and a range of stakeholders. The goal of the ATRAC Framework is to reduce smoking prevalence and the harmful impacts of tobacco use among Aboriginal people and communities in NSW. The framework includes reviews of relevant evidence and recommended actions, organised under six areas: leadership, partnerships and coordination; community action, awareness and engagement; workforce development; supportive environments; quitting support; and evidence, evaluation and research. The framework stresses that, to be successful, Aboriginal tobacco resistance and control programs and activities need to be evidence based, coordinated, integrated and involve Aboriginal people and Aboriginal community controlled health organisations in all aspects, from development through to implementation and evaluation. Consultations and evidence reviews highlight the importance of workforce support and development, including the ongoing need for more workers specialising in Aboriginal tobacco resistance and control, as well as ongoing training for all staff involved in delivering care to Aboriginal people. Other key strategies identified in the framework include improving access to nicotine replacement therapy and other medications to support quitting; supporting, strengthening and building on existing innovative community-based programs; and further developing the evidence base. The AHandMRC and the Ministry will continue to work in partnership to drive the use of the ATRAC Framework by all people

  3. Can coordination variability identify performance factors and skill level in competitive sport? The case of race walking

    Institute of Scientific and Technical Information of China (English)

    Dario Cazzola; Gaspare Pavei; Ezio Preatoni

    2016-01-01

    Background: Marginal changes in the execution of competitive sports movements can represent a significant change for performance success. However, such differences may emerge only at certain execution intensities and are not easily detectable through conventional biomechanical techniques. This study aimed to investigate if and how competition standard and progression speed affect race walking kinematics from both a conventional and a coordination variability perspective. Methods: Fifteen experienced athletes divided into three groups (elite, international, and national) were studied while race walking on a treadmill at two different speeds (12.0 and 15.5 km/h). Basic gait parameters, the angular displacement of the pelvis and lower limbs, and the variability in continuous relative phase between six different joint couplings were analyzed. Results: Most of the spatio-temporal, kinematic, and coordination variability measures proved sensitive to the change in speed. Conversely, non-linear dynamics measures highlighted differences between athletes of different competition standard when conventional analytical tools were not able to discriminate between different skill levels. Continuous relative phase variability was higher for national level athletes than international and elite in two couplings (pelvis obliquity—hip flex/extension and pelvis rotation—ankle dorsi/plantarflexion) and gait phases (early stance for the first coupling, propulsive phase for the second) that are deemed fundamental for correct technique and performance. Conclusion: Measures of coordination variability showed to be a more sensitive tool for the fine detection of skill-dependent factors in competitive race walking, and showed good potential for being integrated in the assessment and monitoring of sports motor abilities.

  4. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    NARCIS (Netherlands)

    Y. Zha; J.A. Westerhuis; B. Muilwijk; K.M. Overkamp; B.M. Nijmeijer; L. Coulier; A.K. Smilde; P.J. Punt

    2014-01-01

    BACKGROUND: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates. RESULTS: We studied the co

  5. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    NARCIS (Netherlands)

    Zha, Y.; Westerhuis, J.A.; Muilwijk, B.; Overkamp, K.M.; Nijmeijer, B.M.; Coulier, L.; Smilde, A.K.; Punt, P.J.

    2014-01-01

    Background: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates.Results: We studied the com

  6. An iterative neighborhood search approach for minimum zone circularity evaluation from coordinate measuring machine data

    International Nuclear Information System (INIS)

    An iterative neighborhood search approach (INSA) was proposed to precisely evaluate the circularity error under minimum zone conditions without directly solving nonlinear equations from coordinate measurement machine (CMM) data. The method starts with calculating the initial location and radius of an initial circular search scope. The location is the center of the circle based on an approximate least-squares method of all measurement data points uniformly sampled around the circle, and the radius is the circularity error value by using the approximate center as the datum center of two concentric circles enclosing all measurement data points. Then the circular search scope was divided according to some concentric circles and radials with some radius and angle step lengths. Intersections of the circles and radials were candidate centers for circularity evaluation under the minimum zone criteria. An optimal center with minimum circularity error value was picked out as a new location of the search scope. The distance from the old location was the radius of the new search scope. Further it was divided and the intersections were evaluated until the optimal solution was met. Some examples in the literature were used to verify the validity of this method. The results are the same as or better than those minimum zone solutions adopted from previous work, and computation time is no more than 0.07 s implementing on an IBM ThinkPad R40 laptop for all examples. The computation and comparison show that the proposed INSA is a precise, fast, convergent and simple approach which solved circularity evaluation problems effectively. (technical design note)

  7. Selection Effects in Identifying Magnetic Clouds and the Importance of the Closest Approach Parameter

    Science.gov (United States)

    Lepping, R. P.; Wu, Chin-Chun

    2010-01-01

    This study is motivated by the unusually low number of magnetic clouds (MCs) that are strictly identified within interplanetary coronal mass ejections (ICMEs), as observed at 1 AU; this is usually estimated to be around 30% or lower. But a looser definition of MCs may significantly increase this percentage. Another motivation is the unexpected shape of the occurrence distribution of the observers' "closest approach distances" (measured from a MC's axis, and called CA) which drops off somewhat rapidly as |CA| (in % of MC radius) approaches 100%, based on earlier studies. We suggest, for various geometrical and physical reasons, that the |CA|-distribution should be somewhere between a uniform one and the one actually observed, and therefore the 30% estimate should be higher. So we ask, When there is a failure to identify a MC within an ICME, is it occasionally due to a large |CA| passage, making MC identification more difficult, i.e., is it due to an event selection effect? In attempting to answer this question we examine WIND data to obtain an accurate distribution of the number of MCs vs. |CA| distance, whether the event is ICME-related or not, where initially a large number of cases (N=98) are considered. This gives a frequence distribution that is far from uniform, confirming earlier studies. This along with the fact that there are many ICME identification-parameters that do not depend on |CA| suggest that, indeed an MC event selection effect may explain at least part of the low ratio of (No. MCs)/(No. ICMEs). We also show that there is an acceptable geometrical and physical consistency in the relationships for both average "normalized" magnetic field intensity change and field direction change vs. |CA| within a MC, suggesting that our estimates of |CA|, B(sub 0) (magnetic field intensity on the axis), and choice of a proper "cloud coordinate" system (all needed in the analysis) are acceptably accurate. Therefore the MC fitting model (Lepping et al., 1990) is

  8. Selection effects in identifying magnetic clouds and the importance of the closest approach parameter

    Directory of Open Access Journals (Sweden)

    R. P. Lepping

    2010-08-01

    Full Text Available This study is motivated by the unusually low number of magnetic clouds (MCs that are strictly identified within interplanetary coronal mass ejections (ICMEs, as observed at 1 AU; this is usually estimated to be around 30% or lower. But a looser definition of MCs may significantly increase this percentage. Another motivation is the unexpected shape of the occurrence distribution of the observers' "closest approach distances" (measured from a MC's axis, and called CA which drops off somewhat rapidly as |CA| (in % of MC radius approaches 100%, based on earlier studies. We suggest, for various geometrical and physical reasons, that the |CA|-distribution should be somewhere between a uniform one and the one actually observed, and therefore the 30% estimate should be higher. So we ask, When there is a failure to identify a MC within an ICME, is it occasionally due to a large |CA| passage, making MC identification more difficult, i.e., is it due to an event selection effect? In attempting to answer this question we examine WIND data to obtain an accurate distribution of the number of MCs vs. |CA| distance, whether the event is ICME-related or not, where initially a large number of cases (N=98 are considered. This gives a frequence distribution that is far from uniform, confirming earlier studies. This along with the fact that there are many ICME identification-parameters that do not depend on |CA| suggest that, indeed an MC event selection effect may explain at least part of the low ratio of (No. MCs/(No. ICMEs. We also show that there is an acceptable geometrical and physical consistency in the relationships for both average "normalized" magnetic field intensity change and field direction change vs. |CA| within a MC, suggesting that our estimates of |CA|, BO (magnetic field intensity on the axis, and choice of a proper "cloud coordinate" system (all needed in the analysis are acceptably accurate. Therefore, the MC

  9. Computational Approaches for Mining GRO-Seq Data to Identify and Characterize Active Enhancers.

    Science.gov (United States)

    Nagari, Anusha; Murakami, Shino; Malladi, Venkat S; Kraus, W Lee

    2017-01-01

    Transcriptional enhancers are DNA regulatory elements that are bound by transcription factors and act to positively regulate the expression of nearby or distally located target genes. Enhancers have many features that have been discovered using genomic analyses. Recent studies have shown that active enhancers recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs (eRNAs). GRO-seq, a method for identifying the location and orientation of all actively transcribing RNA polymerases across the genome, is a powerful approach for monitoring nascent enhancer transcription. Furthermore, the unique pattern of enhancer transcription can be used to identify enhancers in the absence of any information about the underlying transcription factors. Here, we describe the computational approaches required to identify and analyze active enhancers using GRO-seq data, including data pre-processing, alignment, and transcript calling. In addition, we describe protocols and computational pipelines for mining GRO-seq data to identify active enhancers, as well as known transcription factor binding sites that are transcribed. Furthermore, we discuss approaches for integrating GRO-seq-based enhancer data with other genomic data, including target gene expression and function. Finally, we describe molecular biology assays that can be used to confirm and explore further the function of enhancers that have been identified using genomic assays. Together, these approaches should allow the user to identify and explore the features and biological functions of new cell type-specific enhancers. PMID:27662874

  10. Internal pressure gradient errors in sigma-coordinate ocean models: The finite volume and weighted approaches

    OpenAIRE

    Pedersen, Helene Hisken

    2010-01-01

    Terrain-following (sigma-coordinate) models are widely used. They are often advantageous when dealing with large variations in topography, and give an accurate representation of the bottom and top boundary layers. However, near steep topography, the use of these coordinates can lead to a large error in the internal pressure gradient force. Using finite differences is the traditional way of discretising the equations. However, it is possible to integrate over horizontal cells by using a fi...

  11. A Multi-Atlas Labeling Approach for Identifying Subject-Specific Functional Regions of Interest.

    Science.gov (United States)

    Huang, Lijie; Zhou, Guangfu; Liu, Zhaoguo; Dang, Xiaobin; Yang, Zetian; Kong, Xiang-Zhen; Wang, Xu; Song, Yiying; Zhen, Zonglei; Liu, Jia

    2016-01-01

    The functional region of interest (fROI) approach has increasingly become a favored methodology in functional magnetic resonance imaging (fMRI) because it can circumvent inter-subject anatomical and functional variability, and thus increase the sensitivity and functional resolution of fMRI analyses. The standard fROI method requires human experts to meticulously examine and identify subject-specific fROIs within activation clusters. This process is time-consuming and heavily dependent on experts' knowledge. Several algorithmic approaches have been proposed for identifying subject-specific fROIs; however, these approaches cannot easily incorporate prior knowledge of inter-subject variability. In the present study, we improved the multi-atlas labeling approach for defining subject-specific fROIs. In particular, we used a classifier-based atlas-encoding scheme and an atlas selection procedure to account for the large spatial variability across subjects. Using a functional atlas database for face recognition, we showed that with these two features, our approach efficiently circumvented inter-subject anatomical and functional variability and thus improved labeling accuracy. Moreover, in comparison with a single-atlas approach, our multi-atlas labeling approach showed better performance in identifying subject-specific fROIs.

  12. AbsIDconvert: An absolute approach for converting genetic identifiers at different granularities

    Directory of Open Access Journals (Sweden)

    Mohammad Fahim

    2012-09-01

    Full Text Available Abstract Background High-throughput molecular biology techniques yield vast amounts of data, often by detecting small portions of ribonucleotides corresponding to specific identifiers. Existing bioinformatic methodologies categorize and compare these elements using inferred descriptive annotation given this sequence information irrespective of the fact that it may not be representative of the identifier as a whole. Results All annotations, no matter the granularity, can be aligned to genomic sequences and therefore annotated by genomic intervals. We have developed AbsIDconvert, a methodology for converting between genomic identifiers by first mapping them onto a common universal coordinate system using an interval tree which is subsequently queried for overlapping identifiers. AbsIDconvert has many potential uses, including gene identifier conversion, identification of features within a genomic region, and cross-species comparisons. The utility is demonstrated in three case studies: 1 comparative genomic study mapping plasmodium gene sequences to corresponding human and mosquito transcriptional regions; 2 cross-species study of Incyte clone sequences; and 3 analysis of human Ensembl transcripts mapped by Affymetrix®; and Agilent microarray probes. AbsIDconvert currently supports ID conversion of 53 species for a given list of input identifiers, genomic sequence, or genome intervals. Conclusion AbsIDconvert provides an efficient and reliable mechanism for conversion between identifier domains of interest. The flexibility of this tool allows for custom definition identifier domains contingent upon the availability and determination of a genomic mapping interval. As the genomes and the sequences for genetic elements are further refined, this tool will become increasingly useful and accurate. AbsIDconvert is freely available as a web application or downloadable as a virtual machine at: http://bioinformatics.louisville.edu/abid/.

  13. Applying Hybrid Heuristic Approach to Identify Contaminant Source Information in Transient Groundwater Flow Systems

    Directory of Open Access Journals (Sweden)

    Hund-Der Yeh

    2014-01-01

    Full Text Available Simultaneous identification of the source location and release history in aquifers is complicated and time-consuming if the release of groundwater contaminant source varies in time. This paper presents an approach called SATSO-GWT to solve complicated source release problems which contain the unknowns of three location coordinates and several irregular release periods and concentrations. The SATSO-GWT combines with ordinal optimization algorithm (OOA, roulette wheel approach, and a source identification algorithm called SATS-GWT. The SATS-GWT was developed based on simulated annealing, tabu search, and three-dimensional groundwater flow and solute transport model MD2K-GWT. The OOA and roulette wheel method are utilized mainly to reduce the size of feasible solution domain and accelerate the identification of the source information. A hypothetic site with one contaminant source location and two release periods is designed to assess the applicability of the present approach. The results indicate that the performance of SATSO-GWT is superior to that of SATS-GWT. In addition, the present approach works very effectively in dealing with the cases which have different initial guesses of source location and measurement errors in the monitoring points as well as problems with large suspicious areas and several source release periods and concentrations.

  14. A review of approaches to identifying patient phenotype cohorts using electronic health records

    OpenAIRE

    Shivade, Chaitanya; Raghavan, Preethi; Fosler-Lussier, Eric; Embi, Peter J; Elhadad, Noemie; Johnson, Stephen B.; Lai, Albert M.

    2013-01-01

    Objective To summarize literature describing approaches aimed at automatically identifying patients with a common phenotype. Materials and methods We performed a review of studies describing systems or reporting techniques developed for identifying cohorts of patients with specific phenotypes. Every full text article published in (1) Journal of American Medical Informatics Association, (2) Journal of Biomedical Informatics, (3) Proceedings of the Annual American Medical Informatics Associatio...

  15. Artificial neural network approach for atomic coordinate prediction of carbon nanotubes

    Science.gov (United States)

    Acı, Mehmet; Avcı, Mutlu

    2016-07-01

    In this paper, four artificial neural network (ANN) models [i.e., feed-forward neural network (FFNN), function fitting neural network (FITNET), cascade-forward neural network (CFNN) and generalized regression neural network] have been developed for atomic coordinate prediction of carbon nanotubes (CNTs). The research reported in this study has two primary objectives: (1) to develop ANN prediction models that calculate atomic coordinates of CNTs instead of using any simulation software and (2) to use results of the ANN models as an initial value of atomic coordinates for reducing number of iterations in calculation process. The dataset consisting of 10,721 data samples was created by combining the atomic coordinates of elements and chiral vectors using BIOVIA Materials Studio CASTEP (CASTEP) software. All prediction models yield very low mean squared normalized error and mean absolute error rates. Multiple correlation coefficient (R) results of FITNET, FFNN and CFNN models are close to 1. Compared with CASTEP, calculation times decrease from days to minutes. It would seem possible to predict CNTs' atomic coordinates using ANN models can be successfully used instead of mathematical calculations.

  16. Accurate Simulation of Resonance-Raman Spectra of Flexible Molecules: An Internal Coordinates Approach.

    Science.gov (United States)

    Baiardi, Alberto; Bloino, Julien; Barone, Vincenzo

    2015-07-14

    The interpretation and analysis of experimental resonance-Raman (RR) spectra can be significantly facilitated by vibronic computations based on reliable quantum-mechanical (QM) methods. With the aim of improving the description of large and flexible molecules, our recent time-dependent formulation to compute vibrationally resolved electronic spectra, based on Cartesian coordinates, has been extended to support internal coordinates. A set of nonredundant delocalized coordinates is automatically generated from the molecular connectivity thanks to a new general and robust procedure. In order to validate our implementation, a series of molecules has been used as test cases. Among them, rigid systems show that normal modes based on Cartesian and delocalized internal coordinates provide equivalent results, but the latter set is much more convenient and reliable for systems characterized by strong geometric deformations associated with the electronic transition. The so-called Z-matrix internal coordinates, which perform well for chain molecules, are also shown to be poorly suited in the presence of cycles or nonstandard structures.

  17. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  18. New General Approach for Normally Ordering Coordinate-Momentum Operator Functions

    Science.gov (United States)

    Xu, Shi-Min; Xu, Xing-Lei; Li, Hong-Qi; Fan, Hong-Yi

    2016-09-01

    By virtue of integration technique within ordered product of operators and Dirac's representation theory we find a new general formula for normally ordering coordinate-momentum operator functions, that is f(ghat {{Q}}+hhat {P})= :exp [{g2+h2 over 4}{{partial 2} over {partial (ghat {{Q}}+hhat {P})2}}]f(ghat {{Q}}+hhat {P}):, where hat {Q} and hat {P} are the coordinate operator and momentum operator respectively, the symbol :: denotes normal ordering. Using this formula we can derive a series of new relations about Hermite polynomial and Laguerre polynomial, as well as some new differential relations.

  19. Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

    DEFF Research Database (Denmark)

    Bream, Elise N A; Leppellere, Cara R; Cooper, Margaret E;

    2013-01-01

    Background:The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.Methods:We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were...

  20. A goal-oriented approach to identify and engineer ;and use systems.

    NARCIS (Netherlands)

    Hengsdijk, H.; Ittersum, van M.K.

    2002-01-01

    This paper describes a formalized approach to identify and engineer future-oriented land use systems. Such land use systems can be used to explore options for strategic decision making with respect to land use policy and to do ex-ante assessment of land use alternatives to be further tested or devel

  1. Genomic approaches for identifying DNA damage response pathways in S. cerevisiae

    NARCIS (Netherlands)

    Chang, Michael; Parsons, Ainslie B; Sheikh, Bilal H; Boone, Charles; Brown, Grant W

    2006-01-01

    DNA damage response pathways have been studied extensively in the budding yeast Saccharomyces cerevisiae, yet new genes with roles in the DNA damage response are still being identified. In this chapter we describe the use of functional genomic approaches in the identification of DNA damage response

  2. Identifying Core Mobile Learning Faculty Competencies Based Integrated Approach: A Delphi Study

    Science.gov (United States)

    Elbarbary, Rafik Said

    2015-01-01

    This study is based on the integrated approach as a concept framework to identify, categorize, and rank a key component of mobile learning core competencies for Egyptian faculty members in higher education. The field investigation framework used four rounds Delphi technique to determine the importance rate of each component of core competencies…

  3. Motivating Children with Developmental Coordination Disorder in School Physical Education: The Self-Determination Theory Approach

    Science.gov (United States)

    Katartzi, Ermioni S.; Vlachopoulos, Symeon P.

    2011-01-01

    The purpose of the current article is to highlight the potential of self-determination theory (SDT) to inform the teaching practices of physical education (PE) teachers. Such practices may enhance motivational levels for participation in physical activity (PA) for children with developmental coordination disorder (DCD). First, we review the…

  4. A Data-Flow Based Coordination Approach to Concurrent Software Engineering

    NARCIS (Netherlands)

    F. Penczek; W. Cheng; C. Grelck; R. Kirner; B. Scheuermann; A. Shafarenko

    2012-01-01

    In this paper we present S-Net, a coordination language based on dataflow principles, intended for design of concurrent software. The language is introduced and then used for programming a concurrent solver for a combinatorial optimisation problem. We present the analysis and tracing facilities of o

  5. Approaches to CETA Vocational Education Coordination at the District and State Level.

    Science.gov (United States)

    Jacobson, Thomas J.

    Both district and state-level programs have been implemented in the state of California to facilitate the coordination between CETA (Comprehensive Employment and Training Act) and vocational education. The Grossmont Union High School District established the Director of Grants and Contracts/School Improvement position to develop an internal…

  6. Quantitative and qualitative approaches to identifying migration chronology in a continental migrant.

    Directory of Open Access Journals (Sweden)

    William S Beatty

    Full Text Available The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international, whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result

  7. Quantitative and qualitative approaches to identifying migration chronology in a continental migrant

    Science.gov (United States)

    Beatty, William S.; Kesler, Dylan C.; Webb, Elisabeth B.; Raedeke, Andrew H.; Naylor, Luke W.; Humburg, Dale D.

    2013-01-01

    The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted

  8. A cross-species bi-clustering approach to identifying conserved co-regulated genes

    Science.gov (United States)

    Sun, Jiangwen; Jiang, Zongliang; Tian, Xiuchun; Bi, Jinbo

    2016-01-01

    Motivation: A growing number of studies have explored the process of pre-implantation embryonic development of multiple mammalian species. However, the conservation and variation among different species in their developmental programming are poorly defined due to the lack of effective computational methods for detecting co-regularized genes that are conserved across species. The most sophisticated method to date for identifying conserved co-regulated genes is a two-step approach. This approach first identifies gene clusters for each species by a cluster analysis of gene expression data, and subsequently computes the overlaps of clusters identified from different species to reveal common subgroups. This approach is ineffective to deal with the noise in the expression data introduced by the complicated procedures in quantifying gene expression. Furthermore, due to the sequential nature of the approach, the gene clusters identified in the first step may have little overlap among different species in the second step, thus difficult to detect conserved co-regulated genes. Results: We propose a cross-species bi-clustering approach which first denoises the gene expression data of each species into a data matrix. The rows of the data matrices of different species represent the same set of genes that are characterized by their expression patterns over the developmental stages of each species as columns. A novel bi-clustering method is then developed to cluster genes into subgroups by a joint sparse rank-one factorization of all the data matrices. This method decomposes a data matrix into a product of a column vector and a row vector where the column vector is a consistent indicator across the matrices (species) to identify the same gene cluster and the row vector specifies for each species the developmental stages that the clustered genes co-regulate. Efficient optimization algorithm has been developed with convergence analysis. This approach was first validated on

  9. A comparison of approaches for finding minimum identifying codes on graphs

    Science.gov (United States)

    Horan, Victoria; Adachi, Steve; Bak, Stanley

    2016-05-01

    In order to formulate mathematical conjectures likely to be true, a number of base cases must be determined. However, many combinatorial problems are NP-hard and the computational complexity makes this research approach difficult using a standard brute force approach on a typical computer. One sample problem explored is that of finding a minimum identifying code. To work around the computational issues, a variety of methods are explored and consist of a parallel computing approach using MATLAB, an adiabatic quantum optimization approach using a D-Wave quantum annealing processor, and lastly using satisfiability modulo theory (SMT) and corresponding SMT solvers. Each of these methods requires the problem to be formulated in a unique manner. In this paper, we address the challenges of computing solutions to this NP-hard problem with respect to each of these methods.

  10. A coordinated approach to cutaneous wound healing: vibrational microscopy and molecular biology.

    Science.gov (United States)

    Andrew Chan, K L; Zhang, Guojin; Tomic-Canic, Marjana; Stojadinovic, Olivera; Lee, Brian; Flach, Carol R; Mendelsohn, Richard

    2008-10-01

    The repair of cutaneous wounds in the adult body involves a complex series of spatially and temporally organized processes to prevent infection and restore homeostasis. Three characteristic phases of wound repair (inflammation, proliferation including re-epithelialization and remodelling) overlap in time and space. We have utilized a human skin wound-healing model to correlate changes in genotype and pheno-type with infrared (IR) and confocal Raman spectroscopic images during the re-epithelialization of excisional wounds. The experimental protocols validated as IR images clearly delineate the keratin-rich migrating epithelial tongue from the collagen-rich wound bed. Multivariate statistical analysis of IR datasets acquired 6 days post-wounding reveal subtle spectral differences that map to distinct spatial distributions, which are correlated with immunofluorescent staining patterns of different keratin types. Images computed within collagen-rich regions expose complementary spatial patterns and identify elastin in the wound bed. The temporal sequence of events is explored through a comparison of gene array analysis with confocal Raman microscopy. Our approach demonstrates the feasibility of acquiring detailed molecular structure information from the various proteins and their subclasses involved in the wound-healing process.

  11. Crude to leads: a triple-pronged direct NMR approach in coordination with docking simulation.

    Science.gov (United States)

    Tanoli, Sheraz A K; Tanoli, Nazish U; Bondancia, Tatiani M; Usmani, Saman; Kerssebaum, Rainer; Ferreira, Antonio G; Fernandes, Joao B; Ul-Haq, Zaheer

    2013-09-01

    The screening of compounds that bind to the target of interest (specific proteins) plays a vital role in drug discovery. Usually, the identification of biologically active compounds is done from a library of structurally known compounds. However, we successfully illustrate here, that NMR techniques including saturation transfer difference (STD), transfer nuclear Overhauser spectroscopy (TrNOESY) and STD-TOCSY (total correlation spectroscopy) in combination with separation methods not only enable the rapid and comprehensive screening of active components, but also their unequivocal structural characterization. Furthermore, a time saving for the recognition of leads is also possible with this application. To probe the binding studies, a hydroethanolic fraction of crude extract (1 mg) from natural product (Rauia resinous) was used for the initial assessment with BSA protein. The docking simulation was performed with BSA in the region of Thr190, Arg198, Arg217, Trp213, Arg256, Ala290 and Tyr451 to further refine the active compound towards the leads. Docking results mimic binding as identified by STD, Tr-NOESY and STD-TOCSY. Isovetexine-2-rhamnosoide (2) was found to be most active through group epitope mapping results as well as the docking simulation with relative free energy of -7.2770. This experiment provided excellent results through the direct NMR screening method. Using Bovine Serum Albumin as a reference, we illustrate that this approach offers an excellent way for the first hand detection of the active constituents/inhibitors from natural remedies used in folk medicinal treatments.

  12. Chameleons in imagined conversations: A new approach to understanding coordination of linguistic style in dialogs

    CERN Document Server

    Danescu-Niculescu-Mizil, Cristian

    2011-01-01

    Conversational participants tend to immediately and unconsciously adapt to each other's language styles: a speaker will even adjust the number of articles and other function words in their next utterance in response to the number in their partner's immediately preceding utterance. This striking level of coordination is thought to have arisen as a way to achieve social goals, such as gaining approval or emphasizing difference in status. But has the adaptation mechanism become so deeply embedded in the language-generation process as to become a reflex? We argue that fictional dialogs offer a way to study this question, since authors create the conversations but don't receive the social benefits (rather, the imagined characters do). Indeed, we find significant coordination across many families of function words in our large movie-script corpus. We also report suggestive preliminary findings on the effects of gender and other features; e.g., surprisingly, for articles, on average, characters adapt more to females...

  13. A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

    Science.gov (United States)

    Blasius, Clemens K; Intorp, Sebastian N; Wadepohl, Hubert

    2016-01-01

    Summary We report the modular synthesis of three different types of neutral κ2-P,N-ligands comprising an imine and a phosphine binding site. These ligands were reacted with rhodium, iridium and palladium metal precursors and the structures of the resulting complexes were elucidated by means of X-ray crystallography. We observed that subtle changes of the ligand backbone have a significant influence on the binding geometry und coordination properties of these bidentate P,N-donors. PMID:27340475

  14. Exact Solution of the Curved Dirac Equation in Polar Coordinates: Master Function Approach

    Directory of Open Access Journals (Sweden)

    H. Panahi

    2015-01-01

    Full Text Available We show that the (2+1 curved Dirac equation in polar coordinates can be transformed into Schrodinger-like differential equation for upper spinor component. We compare this equation with the Schrodinger equation derived from shape invariance property of second order differential equations of mathematical physics. This formalism enables us to determine the electrostatic potential and relativistic energy in terms of master function and corresponding weight function. We also obtain the spinor wave function in terms of orthogonal polynomials.

  15. A novel pattern mining approach for identifying cognitive activity in EEG based functional brain networks.

    Science.gov (United States)

    Thilaga, M; Vijayalakshmi, R; Nadarajan, R; Nandagopal, D

    2016-06-01

    The complex nature of neuronal interactions of the human brain has posed many challenges to the research community. To explore the underlying mechanisms of neuronal activity of cohesive brain regions during different cognitive activities, many innovative mathematical and computational models are required. This paper presents a novel Common Functional Pattern Mining approach to demonstrate the similar patterns of interactions due to common behavior of certain brain regions. The electrode sites of EEG-based functional brain network are modeled as a set of transactions and node-based complex network measures as itemsets. These itemsets are transformed into a graph data structure called Functional Pattern Graph. By mining this Functional Pattern Graph, the common functional patterns due to specific brain functioning can be identified. The empirical analyses show the efficiency of the proposed approach in identifying the extent to which the electrode sites (transactions) are similar during various cognitive load states.

  16. Pathways to Energy from Inertial Fusion. An Integrated Approach. Report of a Coordinated Research Project 2006-2010

    International Nuclear Information System (INIS)

    The IAEA has continuously demonstrated its commitment to supporting the development of safe and environmentally clean nuclear fusion energy. Statistics show that at the current rate of energy consumption, fusion energy would remain an inexhaustible energy source for humankind for millions of years. Furthermore, some of the existing and foreseen risks - such as nuclear waste disposal and rising greenhouse gas emissions from the use of fossil fuels - can also be reduced. In the quest for fusion energy, two main lines of research and development are currently being pursued worldwide, namely the inertial and the magnetic confinement fusion concepts. For both approaches, the IAEA has conducted coordinated research activities focusing on specific physics and technological issues relevant the establishment of the knowledge base and foundation for the design and construction of fusion power plants. This report describes the recent research and technological developments and challenges in inertial fusion energy within the framework of such a coordinated research effort. The coordinated research project on Pathways to Energy from Inertial Fusion: An Integrated Approach was initiated in 2006 and concluded in 2010. The project involved experts and institutions from 16 Member States, addressing issues relevant to advancing inertial fusion energy research and development in its practical applications. The key topics addressed include: (i) high repetition rate, low cost, high efficiency ignition drivers; (ii) beam-matter/beam-plasma interaction related to inertial fusion target physics; (iii) target fusion chamber coupling and interface; and (iv) integrated inertial fusion power plant design. Participants in this coordinated research project have contributed 17 detailed research and technology progress reports of work performed at national and international levels. This report compiles all these reports while highlighting the various achievements.

  17. A Likelihood-Based Approach to Identifying Contaminated Food Products Using Sales Data: Performance and Challenges

    OpenAIRE

    Kaufman, James; Lessler, Justin; Harry, April; Edlund, Stefan; Hu, Kun; Douglas, Judith; Thoens, Christian; Appel, Bernd; Käsbohrer, Annemarie; Filter, Matthias

    2014-01-01

    Foodborne disease outbreaks of recent years demonstrate that due to increasingly interconnected supply chains these type of crisis situations have the potential to affect thousands of people, leading to significant healthcare costs, loss of revenue for food companies, and—in the worst cases—death. When a disease outbreak is detected, identifying the contaminated food quickly is vital to minimize suffering and limit economic losses. Here we present a likelihood-based approach that has the pote...

  18. A likelihood-based approach to identifying contaminated food products using sales data: performance and challenges.

    OpenAIRE

    James Kaufman; Justin Lessler; April Harry; Stefan Edlund; Kun Hu; Judith Douglas; Christian Thoens; Bernd Appel; Annemarie Käsbohrer; Matthias Filter

    2014-01-01

    Foodborne disease outbreaks of recent years demonstrate that due to increasingly interconnected supply chains these type of crisis situations have the potential to affect thousands of people, leading to significant healthcare costs, loss of revenue for food companies, and--in the worst cases--death. When a disease outbreak is detected, identifying the contaminated food quickly is vital to minimize suffering and limit economic losses. Here we present a likelihood-based approach that has the po...

  19. A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells

    OpenAIRE

    Visnyei, Koppany; Onodera, Hideyuki; Damoiseaux, Robert; Saigusa, Kuniyasu; Petrosyan, Syuzanna; De Vries, David; Ferrari, Denise; Saxe, Jonathan; Panosyan, Eduard H.; Masterman-Smith, Michael; Mottahedeh, Jack; Bradley, Kenneth A.; Huang, Jing; Sabatti, Chiara; Nakano, Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM) is amongst the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells amongst which a tumor initiating and treatment-resistant subpopulation, here termed GBM stem cells (GSC), have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GSC. The paradigm uses a tissue cult...

  20. 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.

  1. A social institutional approach to identifying generation cohorts in China with a comparison with American consumers

    OpenAIRE

    Kineta H Hung; Flora Fang Gu; Chi Kin (Bennett) Yim

    2007-01-01

    Identifying distinctive target segments is a fundamental challenge faced by international marketers. This paper describes an approach to understanding consumer market structures in an important international market, China, and to segmenting Chinese consumers by integrating insights from generational cohort and social institutional theories. We conduct two empirical studies to verify how China's recent momentous ideological events could give rise to and affect the life experiences of different...

  2. Cloning approaches for identifying aging and longevity-related genes in mammals

    OpenAIRE

    Simoes, Davina C.; Gonos, Efstathios S.

    2008-01-01

    Aging is a phenomenon that affects nearly all animal species. Several studies using different systems have identified a number of processes thought to contribute to the aging phenotype. Many differentially expressed genes have been implicated, but the mechanisms governing mammalian aging (and longevity) are not yet fully understood, and the list of concerned genes is still incomplete and fragmented. Different approaches have been used to clone aging and longevity-related genes. In this articl...

  3. A cross-species bi-clustering approach to identifying conserved co-regulated genes

    OpenAIRE

    Sun, Jiangwen; Jiang, Zongliang; Tian, Xiuchun; Bi, Jinbo

    2016-01-01

    Motivation: A growing number of studies have explored the process of pre-implantation embryonic development of multiple mammalian species. However, the conservation and variation among different species in their developmental programming are poorly defined due to the lack of effective computational methods for detecting co-regularized genes that are conserved across species. The most sophisticated method to date for identifying conserved co-regulated genes is a two-step approach. This approac...

  4. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    OpenAIRE

    Zha, Y; Westerhuis, J.A.; Muilwijk, B.; Overkamp, K.M.; Nijmeijer, B.M.; Coulier, L; Smilde, A.K.; Punt, P J

    2014-01-01

    Background: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates.Results: We studied the composition and fermentability of 24 different biomass hydrolysates. To create diversity, the 24 hydrolysates were prepared from six different biomass types, namely sugar cane bagasse, corn stover, wh...

  5. Water use and quality in life cycle assessment: identifying good practices and developing operational spatial approaches

    OpenAIRE

    Kounina, Anna

    2014-01-01

    Pressure on freshwater resources is increasingly covered by methodological developments addressing freshwater use in the field of Life Cycle Assessment (LCA). These developments ultimately lead to the publication of the ISO 14046 standard to define the principles, requirement and guidelines for a water footprint in August 2014. The objective of this thesis is to foster the application of water footprint by identifying good practices and developing operational approaches to assess and improve ...

  6. A Likelihood-Based Approach to Identifying Contaminated Food Products Using Sales Data: Performance and Challenges

    OpenAIRE

    James Kaufman; Justin Lessler; April Harry; Stefan Edlund; Kun Hu; Judith Douglas; Christian Thoens; Bernd Appel; Annemarie Käsbohrer; Matthias Filter

    2014-01-01

    Foodborne disease outbreaks of recent years demonstrate that due to increasingly interconnected supply chains these type of crisis situations have the potential to affect thousands of people, leading to significant healthcare costs, loss of revenue for food companies, and--in the worst cases--death. When a disease outbreak is detected, identifying the contaminated food quickly is vital to minimize suffering and limit economic losses. Here we present a likelihood-based approach that has the po...

  7. An approach to identify issues affecting ERP implementation in Indian SMEs

    Directory of Open Access Journals (Sweden)

    Rana Basu

    2012-06-01

    Full Text Available Purpose: The purpose of this paper is to present the findings of a study which is based on the results of a comprehensive compilation of literature and subsequent analysis of ERP implementation success issues in context to Indian Small and Medium scale Enterprises (SME’s. This paper attempts to explore the existing literature and highlight those issues on ERP implementation and further to this the researchers applied TOPSIS (Technique for order preference by similarity to ideal solution method to prioritize issues affecting successful implementation of ERP. Design/methodology/approach: Based on the literature review certain issues leading to successful ERP implementation have been identified and to identify key issues Pareto Analysis (80-20 Rule have been applied. Further to extraction of key issues a survey based on TOPSIS was carried out in Indian small and medium scale enterprises. Findings: Based on review of literature 25 issues have been identified and further Pareto analysis has been done to extract key issues which is further prioritized by applying Topsis method. Research limitations/implications: Beside those identified issues there may be other issues that need to be explored. There is scope to enhance this study by taking into consideration different type of industries and by extending number of respondents. Practical implications: By identifying key issues for SMEs, managers can better prioritize issues to make implementation process smooth without disruption. ERP vendors can take inputs from this study to change their implementation approach while targeting small scale enterprises. Originality/value: There is no published literature available which followed a similar approach in identification of the critical issues affecting ERP in small and mid-sized companies in India or in any developing economy.

  8. A Chemical Screening Approach to Identify Novel Key Mediators of Erythroid Enucleation

    Science.gov (United States)

    Wölwer, Christina B.; Pase, Luke B.; Pearson, Helen B.; Gödde, Nathan J.; Lackovic, Kurt; Huang, David C. S.; Russell, Sarah M.; Humbert, Patrick O.

    2015-01-01

    Erythroid enucleation is critical for terminal differentiation of red blood cells, and involves extrusion of the nucleus by orthochromatic erythroblasts to produce reticulocytes. Due to the difficulty of synchronizing erythroblasts, the molecular mechanisms underlying the enucleation process remain poorly understood. To elucidate the cellular program governing enucleation, we utilized a novel chemical screening approach whereby orthochromatic cells primed for enucleation were enriched ex vivo and subjected to a functional drug screen using a 324 compound library consisting of structurally diverse, medicinally active and cell permeable drugs. Using this approach, we have confirmed the role of HDACs, proteasomal regulators and MAPK in erythroid enucleation and introduce a new role for Cyclin-dependent kinases, in particular CDK9, in this process. Importantly, we demonstrate that when coupled with imaging analysis, this approach provides a powerful means to identify and characterize rate limiting steps involved in the erythroid enucleation process. PMID:26569102

  9. Identifying Patients in the Acute Psychiatric Hospital Who May Benefit From a Palliative Care Approach.

    Science.gov (United States)

    Burton, M Caroline; Warren, Mark; Cha, Stephen S; Stevens, Maria; Blommer, Megan; Kung, Simon; Lapid, Maria I

    2016-04-01

    Identifying patients who will benefit from a palliative care approach is the first critical step in integrating palliative with curative therapy. Criteria are established that identify hospitalized medical patients who are near end of life, yet there are no criteria with respect to hospitalized patients with psychiatric disorders. The records of 276 consecutive patients admitted to a dedicated inpatient psychiatric unit were reviewed to identify prognostic criteria predictive of mortality. Mortality predictors were 2 or more admissions in the past year (P = .0114) and older age (P = .0006). Twenty-two percent of patients met National Hospice and Palliative Care Organization noncancer criteria for dementia. Palliative care intervention should be considered when treating inpatients with psychiatric disorders, especially older patients who have a previous hospitalization or history of dementia.

  10. EFSA’s approach to identifying emerging risks in food and feed: taking stock and looking forward

    Directory of Open Access Journals (Sweden)

    Robinson T

    2012-10-01

    Full Text Available

    The Emerging Risks Unit has the responsibility for coordinating EFSA’s activities to establish a capacity for the identification of emerging risks. A process was trialled and further developed during a pilot period of 18 months from 2010-2012. This included the implementation of an operational procedure for emerging risks identification, the assessment of selected data sources, the testing of tools for collecting information, the consolidation of knowledge networks for sharing information and the development of a methodological framework. Specific issues were identified for follow-up activities using an expert judgment approach. These include a study on climate change and the emergence of aflatoxins in cereal crops in the European Union (EU, a European-wide survey on the consumption of energy drinks, a task force on human risk assessment of chemical mixtures, an internal task force on bee health, and a foresight study on the potential impact of omics technologies on food and feed safety risk assessment. These follow-up activities will contribute to the determination of whether the issues identified can indeed give rise to emerging risks. Overall, our experience shows that emerging risks identification requires a high level of expertise due to major data gaps and uncertainties in the evaluation process. Effective networking has proven to be essential for exchanging methods, data and evaluations of emerging risks. The system piloted has shown some potential for the identification of issues that may give rise to emerging risks. Useful knowledge has been gained in the area of gathering and filtering large amounts of information and building knowledge networks on emerging risks. Next steps include the establishment of a standing Working Group (WG on Emerging Risks, the reinforcement of the engagement with Member States and Stakeholders, the fine tuning of the revised methodological framework, and the completion of the projects on the issues

  11. Poisson Coordinates.

    Science.gov (United States)

    Li, Xian-Ying; Hu, Shi-Min

    2013-02-01

    Harmonic functions are the critical points of a Dirichlet energy functional, the linear projections of conformal maps. They play an important role in computer graphics, particularly for gradient-domain image processing and shape-preserving geometric computation. We propose Poisson coordinates, a novel transfinite interpolation scheme based on the Poisson integral formula, as a rapid way to estimate a harmonic function on a certain domain with desired boundary values. Poisson coordinates are an extension of the Mean Value coordinates (MVCs) which inherit their linear precision, smoothness, and kernel positivity. We give explicit formulas for Poisson coordinates in both continuous and 2D discrete forms. Superior to MVCs, Poisson coordinates are proved to be pseudoharmonic (i.e., they reproduce harmonic functions on n-dimensional balls). Our experimental results show that Poisson coordinates have lower Dirichlet energies than MVCs on a number of typical 2D domains (particularly convex domains). As well as presenting a formula, our approach provides useful insights for further studies on coordinates-based interpolation and fast estimation of harmonic functions.

  12. Coordination of pricing and co-op advertising models in supply chain: A game theoretic approach

    Directory of Open Access Journals (Sweden)

    Amin Alirezaei

    2014-01-01

    Full Text Available Co-op advertising is an interactive relationship between manufacturer and retailer(s supply chain and makes up the majority of marketing budget in many product lines for manufacturers and retailers. This paper considers pricing and co-op advertising decisions in two-stage supply chain and develops a monopolistic retailer and duopolistic retailer's model. In these models, the manufacturer and the retailers play the Nash, Manufacturer-Stackelberg and cooperative game to make optimal pricing and co-op advertising decisions. A bargaining model is utilized for determine the best pricing and co-op advertising scheme for achieving full coordination in the supply chain.

  13. Multi-finger coordination in healthy subjects and stroke patients: a mathematical modelling approach

    Directory of Open Access Journals (Sweden)

    Ferrarin Maurizio

    2011-04-01

    Full Text Available Abstract Background Approximately 60% of stroke survivors experience hand dysfunction limiting execution of daily activities. Several methods have been proposed to objectively quantify fingers' joints range of motion (ROM, while few studies exist about multi-finger coordination during hand movements. The present work analysed this aspect, by providing a complete characterization of spatial and temporal aspects of hand movement, through the mathematical modelling of multi-joint finger motion in healthy subjects and stroke patients. Methods Hand opening and closing movements were examined in 12 healthy volunteers and 14 hemiplegic stroke survivors by means of optoelectronic kinematic analysis. The flexion/extension angles of metacarpophalangeal (MCPJ and proximal interphalangeal joints (IPJ of all fingers were computed and mathematically characterized by a four-parameter hyperbolic tangent function. Accuracy of the selected model was analysed by means of coefficient of determination (R2 and root mean square error (RMSE. Test-retest reliability was quantified by intraclass correlation coefficient (ICC and test-retest errors. Comparison between performances of healthy controls and stroke subjects were performed by analysing possible differences in parameters describing angular and temporal aspects of hand kinematics and inter-joint, inter-digit coordination. Results The angular profiles of hand opening and closing were accurately characterized by the selected model, both in healthy controls and in stroke subjects (R2 > 0.973, RMSE 0.75 and remarking errors comparable to those obtained with other methods. Comparison with healthy controls revealed that hemiparetic hand movement was impaired not only in joints ROM but also in the temporal aspects of motion: peak velocities were significantly decreased, inter-digit coordination was reduced of more than 50% and inter-joint coordination patterns were highly disrupted. In particular, the stereotypical

  14. Scattering of electromagnetic waves by spheroidal particles: a novel approach exploiting the scr(T) matrix computed in spheroidal coordinates

    International Nuclear Information System (INIS)

    A method other than the extended-boundary-condition method (EBCM) to compute the T matrix for electromagnetic scattering is presented. The separation-of-variables method (SVM) is used to solve the electromagnetic scattering problem for a spheroidal particle and to derive its scr(T) matrix in spheroidal coordinates. A transformation is developed for transforming the scr(T) matrix in spheroidal coordinates into the corresponding T matrix in spherical coordinates. The T matrix so obtained can be used for analytical calculation of the optical properties of ensembles of randomly oriented spheroids of arbitrary shape by use of an existing method to average over orientational angles. The optical properties obtained with the SVM and the EBCM are compared for different test cases. For mildly aspherical particles the two methods yield indistinguishable results. Small differences appear for highly aspherical particles. The new approach can be used to compute optical properties for arbitrary values of the aspect ratio. To test the accuracy of the expansion coefficients of the spheroidal functions for arbitrary arguments, a new testing method based on the completeness relation of the spheroidal functions is developed. copyright 1998 Optical Society of America

  15. A simple coordinate space approach to three-body problems – Examples: Halo nucleus and double- hypernucleus

    Indian Academy of Sciences (India)

    S Mahapatra; J Nag; D P Sural; S N Mukherjee

    2001-10-01

    We show how to treat the dynamics of an asymmetric three-body system consisting of one heavy and two identical light particles in a simple coordinate space variational approach. The method is constructive and gives an efficient way of resolving a three-body system to an effective two-body system. It is illustrated by explaining the structural properties of some nuclei of current interest, namely halo nuclei and double- hypernuclei. The ansatz used here may be of value in a number of three particle problems of similar nature.

  16. Reverse PCA, a systematic approach for identifying genes important for the physical interaction between protein pairs.

    Directory of Open Access Journals (Sweden)

    Ifat Lev

    Full Text Available Protein-protein interactions (PPIs are of central importance for many areas of biological research. Several complementary high-throughput technologies have been developed to study PPIs. The wealth of information that emerged from these technologies led to the first maps of the protein interactomes of several model organisms. Many changes can occur in protein complexes as a result of genetic and biochemical perturbations. In the absence of a suitable assay, such changes are difficult to identify, and thus have been poorly characterized. In this study, we present a novel genetic approach (termed "reverse PCA" that allows the identification of genes whose products are required for the physical interaction between two given proteins. Our assay starts with a yeast strain in which the interaction between two proteins of interest can be detected by resistance to the drug, methotrexate, in the context of the protein-fragment complementation assay (PCA. Using synthetic genetic array (SGA technology, we can systematically screen mutant libraries of the yeast Saccharomyces cerevisiae to identify those mutations that disrupt the physical interaction of interest. We were able to successfully validate this novel approach by identifying mutants that dissociate the conserved interaction between Cia2 and Mms19, two proteins involved in Iron-Sulfur protein biogenesis and genome stability. This method will facilitate the study of protein structure-function relationships, and may help in elucidating the mechanisms that regulate PPIs.

  17. Identifying genetic signatures of selection in a non-model species, alpine gentian (Gentiana nivalis L.), using a landscape genetic approach

    DEFF Research Database (Denmark)

    Bothwell, H.; Bisbing, S.; Therkildsen, Nina Overgaard;

    2013-01-01

    loci, we compared outlier locus detection methods with a recently-developed landscape genetic approach. We analyzed 157 loci from samples of the alpine herb Gentiana nivalis collected across the European Alps. Principle coordinates of neighbor matrices (PCNM), eigenvectors that quantify multi...... variables identified eight more potentially adaptive loci than models run without spatial variables. 3) When compared to outlier detection methods, the landscape genetic approach detected four of the same loci plus 11 additional loci. 4) Temperature, precipitation, and solar radiation were the three major......-scale spatial variation present in a data set, were incorporated into a landscape genetic approach relating AFLP frequencies with 23 environmental variables. Four major findings emerged. 1) Fifteen loci were significantly correlated with at least one predictor variable (R adj 2 > 0.5). 2) Models including PCNM...

  18. Coordinating energy allocation and process performance using an agent-based approach

    DEFF Research Database (Denmark)

    Umair, Aisha; Clausen, Anders; Jørgensen, Bo Nørregaard

    2015-01-01

    arises when the energy resources demanded by the process domain are either lesser or greater than the resources allocated in the energy domain. This situation may lead to suboptimal process performance and inefficient usage of energy. Solving this allocation problem requires a coordination and control...... mechanism that can balance allocation and demand. In this paper, we propose a novel agent-based software system for solving cooperative control problems. The system produces a Pareto-optimal energy allocation for the process domain while striving to achieve a group objective for balancing the individual......Energy efficient systems are receiving worldwide attention in response to the negative effects of global warming. Energy efficient systems are concerned with allocation of adequate resources in the energy domain to meet the energy demand in the process domain. In allocation, a balancing problem...

  19. Motivating children with developmental coordination disorder in school physical education: the self-determination theory approach.

    Science.gov (United States)

    Katartzi, Ermioni S; Vlachopoulos, Symeon P

    2011-01-01

    The purpose of the current article is to highlight the potential of self-determination theory (SDT) to inform the teaching practices of physical education (PE) teachers. Such practices may enhance motivational levels for participation in physical activity (PA) for children with developmental coordination disorder (DCD). First, we review the research in PE demonstrating links between teachers' interpersonal style, teaching methods, and outcomes relating to both students' motivation and motor skill improvement. Second, we outline the SDT mechanism through which the practices employed by PE teachers to support students' psychological needs for autonomy, competence, and relatedness may effect positive changes in the motivation and the physical activity behaviour of children with DCD. Third, we present an overview of findings on the effectiveness of need-supporting practices used by PE teachers. Fourth, we provide directions for future motivational research using the SDT principles in school physical education for children with DCD.

  20. Identifying Overlapping and Hierarchical Thematic Structures in Networks of Scholarly Papers: A Comparison of Three Approaches

    Science.gov (United States)

    Havemann, Frank; Gläser, Jochen; Heinz, Michael; Struck, Alexander

    2012-01-01

    The aim of this paper is to introduce and assess three algorithms for the identification of overlapping thematic structures in networks of papers. We implemented three recently proposed approaches to the identification of overlapping and hierarchical substructures in graphs and applied the corresponding algorithms to a network of 492 information-science papers coupled via their cited sources. The thematic substructures obtained and overlaps produced by the three hierarchical cluster algorithms were compared to a content-based categorisation, which we based on the interpretation of titles, abstracts, and keywords. We defined sets of papers dealing with three topics located on different levels of aggregation: h-index, webometrics, and bibliometrics. We identified these topics with branches in the dendrograms produced by the three cluster algorithms and compared the overlapping topics they detected with one another and with the three predefined paper sets. We discuss the advantages and drawbacks of applying the three approaches to paper networks in research fields. PMID:22479376

  1. Identifying Overlapping and Hierarchical Thematic Structures in Networks of Scholarly Papers: A Comparison of Three Approaches

    CERN Document Server

    Havemann, Frank; Heinz, Michael; Struck, Alexander

    2011-01-01

    We implemented three recently proposed approaches to the identification of overlapping and hierarchical substructures in graphs and applied the corresponding algorithms to a network of 492 information-science papers coupled via their cited sources. The thematic substructures obtained and overlaps produced by the three hierarchical cluster algorithms were compared to a content-based categorisation, which we based on the interpretation of titles and keywords. We defined sets of papers dealing with three topics located on different levels of aggregation: h-index, webometrics, and bibliometrics. We identified these topics with branches in the dendrograms produced by the three cluster algorithms and compared the overlapping topics they detected with one another and with the three pre-defined paper sets. We discuss the advantages and drawbacks of applying the three approaches to paper networks in research fields.

  2. Identifying the Critical Links in Road Transportation Networks: Centrality-based approach utilizing structural properties

    Energy Technology Data Exchange (ETDEWEB)

    Chinthavali, Supriya [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-04-01

    Surface transportation road networks share structural properties similar to other complex networks (e.g., social networks, information networks, biological networks, and so on). This research investigates the structural properties of road networks for any possible correlation with the traffic characteristics such as link flows those determined independently. Additionally, we define a criticality index for the links of the road network that identifies the relative importance in the network. We tested our hypotheses with two sample road networks. Results show that, correlation exists between the link flows and centrality measures of a link of the road (dual graph approach is followed) and the criticality index is found to be effective for one test network to identify the vulnerable nodes.

  3. A multi-criteria decision making approach to identify a vaccine formulation.

    Science.gov (United States)

    Dewé, Walthère; Durand, Christelle; Marion, Sandie; Oostvogels, Lidia; Devaster, Jeanne-Marie; Fourneau, Marc

    2016-01-01

    This article illustrates the use of a multi-criteria decision making approach, based on desirability functions, to identify an appropriate adjuvant composition for an influenza vaccine to be used in elderly. The proposed adjuvant system contained two main elements: monophosphoryl lipid and α-tocopherol with squalene in an oil/water emulsion. The objective was to elicit a stronger immune response while maintaining an acceptable reactogenicity and safety profile. The study design, the statistical models, the choice of the desirability functions, the computation of the overall desirability index, and the assessment of the robustness of the ranking are all detailed in this manuscript.

  4. An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome.

    Science.gov (United States)

    Guedj, Faycal; Pennings, Jeroen LA; Massingham, Lauren J; Wick, Heather C; Siegel, Ashley E; Tantravahi, Umadevi; Bianchi, Diana W

    2016-01-01

    Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls, and embryonic day 15.5 forebrains from Ts1Cje, Ts65Dn, and Dp16 mice. The new datasets were compared to other publicly available datasets from humans with DS. We used the human Connectivity Map (CMap) database and created a murine adaptation to identify FDA-approved drugs that can rescue affected pathways. USP16 and TTC3 were dysregulated in all affected human cells and two mouse models. DS-associated pathway abnormalities were either the result of gene dosage specific effects or the consequence of a global cell stress response with activation of compensatory mechanisms. CMap analyses identified 56 molecules with high predictive scores to rescue abnormal gene expression in both species. Our novel integrated human/murine systems biology approach identified commonly dysregulated genes and pathways. This can help to prioritize therapeutic molecules on which to further test safety and efficacy. Additional studies in human cells are ongoing prior to pre-clinical prenatal treatment in mice. PMID:27586445

  5. A Coordinated Approach to Communicating Pediatric-Related Information on Pandemic Influenza at the Community Level

    Energy Technology Data Exchange (ETDEWEB)

    HCTT CHE

    2009-12-16

    The purpose of this document is to provide a suggested approach, based on input from pediatric stakeholders, to communicating pediatric-related information on pandemic influenza at the community level in a step-by-step manner.

  6. Approach for Identifying Human Leukocyte Antigen (HLA)-DR Bound Peptides from Scarce Clinical Samples.

    Science.gov (United States)

    Heyder, Tina; Kohler, Maxie; Tarasova, Nataliya K; Haag, Sabrina; Rutishauser, Dorothea; Rivera, Natalia V; Sandin, Charlotta; Mia, Sohel; Malmström, Vivianne; Wheelock, Åsa M; Wahlström, Jan; Holmdahl, Rikard; Eklund, Anders; Zubarev, Roman A; Grunewald, Johan; Ytterberg, A Jimmy

    2016-09-01

    Immune-mediated diseases strongly associating with human leukocyte antigen (HLA) alleles are likely linked to specific antigens. These antigens are presented to T cells in the form of peptides bound to HLA molecules on antigen presenting cells, e.g. dendritic cells, macrophages or B cells. The identification of HLA-DR-bound peptides presents a valuable tool to investigate the human immunopeptidome. The lung is likely a key player in the activation of potentially auto-aggressive T cells prior to entering target tissues and inducing autoimmune disease. This makes the lung of exceptional interest and presents an ideal paradigm to study the human immunopeptidome and to identify antigenic peptides.Our previous investigation of HLA-DR peptide presentation in the lung required high numbers of cells (800 × 10(6) bronchoalveolar lavage (BAL) cells). Because BAL from healthy nonsmokers typically contains 10-15 × 10(6) cells, there is a need for a highly sensitive approach to study immunopeptides in the lungs of individual patients and controls.In this work, we analyzed the HLA-DR immunopeptidome in the lung by an optimized methodology to identify HLA-DR-bound peptides from low cell numbers. We used an Epstein-Barr Virus (EBV) immortalized B cell line and bronchoalveolar lavage (BAL) cells obtained from patients with sarcoidosis, an inflammatory T cell driven disease mainly occurring in the lung. Specifically, membrane complexes were isolated prior to immunoprecipitation, eluted peptides were identified by nanoLC-MS/MS and processed using the in-house developed ClusterMHCII software. With the optimized procedure we were able to identify peptides from 10 × 10(6) cells, which on average correspond to 10.9 peptides/million cells in EBV-B cells and 9.4 peptides/million cells in BAL cells. This work presents an optimized approach designed to identify HLA-DR-bound peptides from low numbers of cells, enabling the investigation of the BAL immunopeptidome from individual patients

  7. Energy-optimised pharmacophore approach to identify potential hotspots during inhibition of Class II HDAC isoforms.

    Science.gov (United States)

    Ganai, Shabir Ahmad; Shanmugam, Karthi; Mahadevan, Vijayalakshmi

    2015-01-01

    Histone deacetylases (HDACs) are conjugated enzymes that modulate chromatin architecture by deacetylating lysine residues on the histone tails leading to transcriptional repression. Pharmacological interventions of these enzymes with small molecule inhibitors called Histone deacetylase inhibitors (HDACi) have shown enhanced acetylation of the genome and are hence emerging as potential targets at the clinic. Type-specific inhibition of Class II HDACs has shown enhanced therapeutic benefits against developmental and neurodegenerative disorders. However, the structural identity of class-specific isoforms limits the potential of their inhibitors in precise targeting of their enzymes. Diverse strategies have been implemented to recognise the features in HDAC enzymes which may help in identifying isoform specificity factors. This work attempts a computational approach that combines in silico docking and energy-optimised pharmacophore (E-pharmacophore) mapping of 18 known HDAC inhibitors and has identified structural variations that regulate their interactions against the six Class II HDAC enzymes considered for the study. This combined approach establishes that inhibitors possessing higher number of aromatic rings in different structural regions might function as potent inhibitors, while inhibitors with scarce ring structures might point to compromised potency. This would aid the rationale for chemical optimisation and design of isoform selective HDAC inhibitors with enhanced affinity and therapeutic efficiency.

  8. An evolutionary genomic approach to identify genes involved in human birth timing.

    Directory of Open Access Journals (Sweden)

    Jevon Plunkett

    2011-04-01

    Full Text Available Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.

  9. Coordinated risk informed regulation: a conceptual approach illustrated by the industry of phytosanitary radiation treatment

    International Nuclear Information System (INIS)

    Regulatory bodies control areas such as health, environment, safety, transportation, finance or any other area of strategic importance to the national sustainable development, where the free activity of economic agents will not lead to socially desirable results. In Brazil, industrial activities impacting on different social and economic segments may be subject to regulation by several governmental agencies, with different cultures, requirements, procedures, and deadlines. To approve an industrial undertaking, most often each regulator analyzes in isolation the aspect of its concern. Also in monitoring and enforcement, the agencies usually act individually. The proliferation and fragmentation of regulation have, in some cases, delayed or even inhibited the development of industrial activities, and thus, working against the very purpose of regulation. This thesis illustrates the current situation with the regulation on food irradiation services, proposes and justifies an organizational structure to enhance coordination among regulatory agencies by aligning their activities and avoiding inconsistencies, overlaps and omissions. This structure comprises, among other mechanisms, a single Internet portal on Federal Regulation, an integrated and dynamic risk analysis and the harmonization of decision-making. The purpose is to promote regulation predictability, regulatory action consistency, optimization of public resources, transparency in the agencies' decision making, and to bring benefits to the entrepreneurs by offering them real-time monitoring and more agile processes. (author)

  10. Direct and heterologous approaches to identify the LET-756/FGF interactome

    Directory of Open Access Journals (Sweden)

    Birnbaum Daniel

    2006-05-01

    Full Text Available Abstract Background Fibroblast growth factors (FGFs are multifunctional proteins that play important roles in cell communication, proliferation and differentiation. However, many aspects of their activities are not well defined. LET-756, one of the two C. elegans FGFs, is expressed throughout development and is essential for worm development. It is both expressed in the nucleus and secreted. Results To identify nuclear factors associated with LET-756, we used three approaches. First, we screened a two-hybrid cDNA library derived from mixed stages worms and from a normalized library, using LET-756 as bait. This direct approach allowed the identification of several binding partners that play various roles in the nucleus/nucleolus, such as PAL-1, a transcription regulator, or RPS-16, a component of the small ribosomal subunit. The interactions were validated by co-immunoprecipitation and determination of their site of occurrence in mammalian cells. Second, because patterns of protein interactions may be conserved throughout species, we searched for orthologs of known mammalian interactors and measured binary interaction with these predicted candidates. We found KIN-3 and KIN-10, the orthologs of CK2α and CK2β, as new partners of LET-756. Third, following the assumption that recognition motifs mediating protein interaction may be conserved between species, we screened a two-hybrid cDNA human library using LET-756 as bait. Among the few FGF partners detected was 14-3-3β. In support of this interaction we showed that the two 14-3-3β orthologous proteins, FTT-1 and FTT-2/PAR-5, interacted with LET-756. Conclusion We have conducted the first extensive search for LET-756 interactors using a multi-directional approach and established the first interaction map of LET-756/FGF with other FGF binding proteins from other species. The interactors identified play various roles in developmental process or basic biochemical events such as ribosome biogenesis.

  11. Identifying functional reorganization of spelling networks: An Individual Peak Probability Comparison Approach.

    Directory of Open Access Journals (Sweden)

    Jeremy Joseph Purcell

    2013-12-01

    Full Text Available Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011; in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE (Turkeltaub et al., 2002. This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual’s activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011 that compares each of a control group’s peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual’s peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual’s activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual’s activation pattern with that of a set of other individuals.

  12. A sequence-based approach to identify reference genes for gene expression analysis

    Directory of Open Access Journals (Sweden)

    Chari Raj

    2010-08-01

    Full Text Available Abstract Background An important consideration when analyzing both microarray and quantitative PCR expression data is the selection of appropriate genes as endogenous controls or reference genes. This step is especially critical when identifying genes differentially expressed between datasets. Moreover, reference genes suitable in one context (e.g. lung cancer may not be suitable in another (e.g. breast cancer. Currently, the main approach to identify reference genes involves the mining of expression microarray data for highly expressed and relatively constant transcripts across a sample set. A caveat here is the requirement for transcript normalization prior to analysis, and measurements obtained are relative, not absolute. Alternatively, as sequencing-based technologies provide digital quantitative output, absolute quantification ensues, and reference gene identification becomes more accurate. Methods Serial analysis of gene expression (SAGE profiles of non-malignant and malignant lung samples were compared using a permutation test to identify the most stably expressed genes across all samples. Subsequently, the specificity of the reference genes was evaluated across multiple tissue types, their constancy of expression was assessed using quantitative RT-PCR (qPCR, and their impact on differential expression analysis of microarray data was evaluated. Results We show that (i conventional references genes such as ACTB and GAPDH are highly variable between cancerous and non-cancerous samples, (ii reference genes identified for lung cancer do not perform well for other cancer types (breast and brain, (iii reference genes identified through SAGE show low variability using qPCR in a different cohort of samples, and (iv normalization of a lung cancer gene expression microarray dataset with or without our reference genes, yields different results for differential gene expression and subsequent analyses. Specifically, key established pathways in lung

  13. Calibrated photostimulated luminescence is an effective approach to identify irradiated orange during storage

    International Nuclear Information System (INIS)

    Photostimulated luminescence (PSL) has been employed as a fast screening method for various irradiated foods. In this study the potential use of PSL was evaluated to identify oranges irradiated with gamma ray, electron beam and X-ray (0–2 kGy) and stored under different conditions for 6 weeks. The effects of light conditions (natural light, artificial light, and dark) and storage temperatures (4 and 20 °C) on PSL photon counts (PCs) during post-irradiation periods were studied. Non-irradiated samples always showed negative values of PCs, while irradiated oranges exhibited intermediate results after first PSL measurements. However, the irradiated samples had much higher PCs. The PCs of all the samples declined as the storage time increased. Calibrated second PSL measurements showed PSL ratio <10 for the irradiated samples after 3 weeks of irradiation confirming their irradiation status in all the storage conditions. Calibrated PSL and sample storage in dark at 4 °C were found out to be most suitable approaches to identify irradiated oranges during storage. - Highlights: • Photostimulatedluminescence (PSL) was studied to identify irradiated orange for quarantine application. • PSL detection efficiency was compared amonggamma,electron, and X irradiation during shelf-life of oranges • PSL properties of samples were characterized by standard samples • Calibrated PSL gave a clear verdict on irradiation extending potential of PSL technique

  14. Aspherical-atom modeling of coordination compounds by single-crystal X-ray diffraction allows the correct metal atom to be identified.

    Science.gov (United States)

    Dittrich, Birger; Wandtke, Claudia M; Meents, Alke; Pröpper, Kevin; Mondal, Kartik Chandra; Samuel, Prinson P; Amin Sk, Nurul; Singh, Amit Pratap; Roesky, Herbert W; Sidhu, Navdeep

    2015-02-01

    Single-crystal X-ray diffraction (XRD) is often considered the gold standard in analytical chemistry, as it allows element identification as well as determination of atom connectivity and the solid-state structure of completely unknown samples. Element assignment is based on the number of electrons of an atom, so that a distinction of neighboring heavier elements in the periodic table by XRD is often difficult. A computationally efficient procedure for aspherical-atom least-squares refinement of conventional diffraction data of organometallic compounds is proposed. The iterative procedure is conceptually similar to Hirshfeld-atom refinement (Acta Crystallogr. Sect. A- 2008, 64, 383-393; IUCrJ. 2014, 1,61-79), but it relies on tabulated invariom scattering factors (Acta Crystallogr. Sect. B- 2013, 69, 91-104) and the Hansen/Coppens multipole model; disordered structures can be handled as well. Five linear-coordinate 3d metal complexes, for which the wrong element is found if standard independent-atom model scattering factors are relied upon, are studied, and it is shown that only aspherical-atom scattering factors allow a reliable assignment. The influence of anomalous dispersion in identifying the correct element is investigated and discussed. PMID:25393218

  15. University Student Death Response Plans Using a Structural Management Approach Provide Effective Coordinated Institutional Action

    Science.gov (United States)

    Cusick, Anne

    2008-01-01

    Student death is an inevitable event in the long life of university communities. Although student death is uncommon, universities need to be able respond in a timely and appropriate way to bring the relationship with a deceased student to a dignified close. This article presents a review of factors previously identified in higher education and…

  16. An affinity pull-down approach to identify the plant cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth

    2013-09-03

    Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.

  17. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2010-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified......, such as legislation, self-regulation and technical approaches. It is intended to promote an effective approach to improve consumer privacy in the mobile advertising domain....

  18. Identifying Risk and Protective Factors in Recidivist Juvenile Offenders: A Decision Tree Approach.

    Science.gov (United States)

    Ortega-Campos, Elena; García-García, Juan; Gil-Fenoy, Maria José; Zaldívar-Basurto, Flor

    2016-01-01

    Research on juvenile justice aims to identify profiles of risk and protective factors in juvenile offenders. This paper presents a study of profiles of risk factors that influence young offenders toward committing sanctionable antisocial behavior (S-ASB). Decision tree analysis is used as a multivariate approach to the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders in Spain. The study sample was made up of the set of juveniles who were charged in a court case in the Juvenile Court of Almeria (Spain). The period of study of recidivism was two years from the baseline. The object of study is presented, through the implementation of a decision tree. Two profiles of risk and protective factors are found. Risk factors associated with higher rates of recidivism are antisocial peers, age at baseline S-ASB, problems in school and criminality in family members. PMID:27611313

  19. Identifying Liver Cancer and Its Relations with Diseases, Drugs, and Genes: A Literature-Based Approach

    Science.gov (United States)

    Song, Min

    2016-01-01

    In biomedicine, scientific literature is a valuable source for knowledge discovery. Mining knowledge from textual data has become an ever important task as the volume of scientific literature is growing unprecedentedly. In this paper, we propose a framework for examining a certain disease based on existing information provided by scientific literature. Disease-related entities that include diseases, drugs, and genes are systematically extracted and analyzed using a three-level network-based approach. A paper-entity network and an entity co-occurrence network (macro-level) are explored and used to construct six entity specific networks (meso-level). Important diseases, drugs, and genes as well as salient entity relations (micro-level) are identified from these networks. Results obtained from the literature-based literature mining can serve to assist clinical applications. PMID:27195695

  20. Identifying Risk and Protective Factors in Recidivist Juvenile Offenders: A Decision Tree Approach

    Science.gov (United States)

    Ortega-Campos, Elena; García-García, Juan; Gil-Fenoy, Maria José; Zaldívar-Basurto, Flor

    2016-01-01

    Research on juvenile justice aims to identify profiles of risk and protective factors in juvenile offenders. This paper presents a study of profiles of risk factors that influence young offenders toward committing sanctionable antisocial behavior (S-ASB). Decision tree analysis is used as a multivariate approach to the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders in Spain. The study sample was made up of the set of juveniles who were charged in a court case in the Juvenile Court of Almeria (Spain). The period of study of recidivism was two years from the baseline. The object of study is presented, through the implementation of a decision tree. Two profiles of risk and protective factors are found. Risk factors associated with higher rates of recidivism are antisocial peers, age at baseline S-ASB, problems in school and criminality in family members. PMID:27611313

  1. Identifying the critical financial ratios for stocks evaluation: A fuzzy delphi approach

    Science.gov (United States)

    Mokhtar, Mazura; Shuib, Adibah; Mohamad, Daud

    2014-12-01

    Stocks evaluation has always been an interesting and challenging problem for both researchers and practitioners. Generally, the evaluation can be made based on a set of financial ratios. Nevertheless, there are a variety of financial ratios that can be considered and if all ratios in the set are placed into the evaluation process, data collection would be more difficult and time consuming. Thus, the objective of this paper is to identify the most important financial ratios upon which to focus in order to evaluate the stock's performance. For this purpose, a survey was carried out using an approach which is based on an expert judgement, namely the Fuzzy Delphi Method (FDM). The results of this study indicated that return on equity, return on assets, net profit margin, operating profit margin, earnings per share and debt to equity are the most important ratios.

  2. A new simplex chemometric approach to identify olive oil blends with potentially high traceability.

    Science.gov (United States)

    Semmar, N; Laroussi-Mezghani, S; Grati-Kamoun, N; Hammami, M; Artaud, J

    2016-10-01

    Olive oil blends (OOBs) are complex matrices combining different cultivars at variable proportions. Although qualitative determinations of OOBs have been subjected to several chemometric works, quantitative evaluations of their contents remain poorly developed because of traceability difficulties concerning co-occurring cultivars. Around this question, we recently published an original simplex approach helping to develop predictive models of the proportions of co-occurring cultivars from chemical profiles of resulting blends (Semmar & Artaud, 2015). Beyond predictive model construction and validation, this paper presents an extension based on prediction errors' analysis to statistically define the blends with the highest predictability among all the possible ones that can be made by mixing cultivars at different proportions. This provides an interesting way to identify a priori labeled commercial products with potentially high traceability taking into account the natural chemical variability of different constitutive cultivars. PMID:27132835

  3. Landing of VTOL UAVs Using a Stationary Robot Manipulator: A New Approach for Coordinated Control

    OpenAIRE

    Maier, Moritz; Kondak, Konstantin

    2015-01-01

    This paper deals with the landing of VTOL UAVs under severe conditions. We present a novel system based on a robot manipulator, which is used to support a UAV in the last, most challenging, landing phase. In this phase, the aerial vehicle is connected to the robot by means of a universal hinge. This allows to decouple the UAV’s orientation from the robot’s end-effector orientation. The main contribution of the paper is a new control approach for the whole system compos...

  4. Chemical proteomics approaches for identifying the cellular targets of natural products.

    Science.gov (United States)

    Wright, M H; Sieber, S A

    2016-05-01

    Covering: 2010 up to 2016Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied "in situ" - in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide-alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss 'competitive mode' approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed.

  5. A non-target approach to identify disinfection byproducts of structurally similar sulfonamide antibiotics.

    Science.gov (United States)

    Wang, Mian; Helbling, Damian E

    2016-10-01

    There is growing concern over the formation of new types of disinfection byproducts (DBPs) from pharmaceuticals and other emerging contaminants during drinking water production. Free chlorine is a widely used disinfectant that reacts non-selectively with organic molecules to form a variety of byproducts. In this research, we aimed to investigate the DBPs formed from three structurally similar sulfonamide antibiotics (sulfamethoxazole, sulfathiazole, and sulfadimethoxine) to determine how chemical structure influences the types of chlorination reactions observed. We conducted free chlorination experiments and developed a non-target approach to extract masses from the experimental dataset that represent the masses of candidate DBPs. Structures were assigned to the candidate DBPs based on analytical data and knowledge of chlorine chemistry. Confidence levels were assigned to each proposed structure according to conventions in the field. In total, 11, 12, and 15 DBP structures were proposed for sulfamethoxazole, sulfathiazole, and sulfadimethoxine, respectively. The structures of the products suggest a variety of reaction types including chlorine substitution, SC cleavage, SN hydrolysis, desulfonation, oxidation/hydroxylation, and conjugation reactions. Some reaction types were common to all of the sulfonamide antibiotics, but unique reaction types were also observed for each sulfonamide antibiotic suggesting that selective prediction of DBP structures of other sulfonamide antibiotics based on chemical structure is unlikely to be possible based on these data alone. This research offers an approach to comprehensively identify DBPs of organic molecules and fills in much needed data on the formation of specific DBPs from three environmentally relevant sulfonamide antibiotics.

  6. Identifying Potential Areas for Siting Interim Nuclear Waste Facilities Using Map Algebra and Optimization Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Omitaomu, Olufemi A [ORNL; Liu, Cheng [ORNL; Cetiner, Sacit M [ORNL; Belles, Randy [ORNL; Mays, Gary T [ORNL; Tuttle, Mark A [ORNL

    2013-01-01

    The renewed interest in siting new nuclear power plants in the United States has brought to the center stage, the need to site interim facilities for long-term management of spent nuclear fuel (SNF). In this paper, a two-stage approach for identifying potential areas for siting interim SNF facilities is presented. In the first stage, the land area is discretized into grids of uniform size (e.g., 100m x 100m grids). For the continental United States, this process resulted in a data matrix of about 700 million cells. Each cell of the matrix is then characterized as a binary decision variable to indicate whether an exclusion criterion is satisfied or not. A binary data matrix is created for each of the 25 siting criteria considered in this study. Using map algebra approach, cells that satisfy all criteria are clustered and regarded as potential siting areas. In the second stage, an optimization problem is formulated as a p-median problem on a rail network such that the sum of the shortest distance between nuclear power plants with SNF and the potential storage sites from the first stage is minimized. The implications of obtained results for energy policies are presented and discussed.

  7. A non-target approach to identify disinfection byproducts of structurally similar sulfonamide antibiotics.

    Science.gov (United States)

    Wang, Mian; Helbling, Damian E

    2016-10-01

    There is growing concern over the formation of new types of disinfection byproducts (DBPs) from pharmaceuticals and other emerging contaminants during drinking water production. Free chlorine is a widely used disinfectant that reacts non-selectively with organic molecules to form a variety of byproducts. In this research, we aimed to investigate the DBPs formed from three structurally similar sulfonamide antibiotics (sulfamethoxazole, sulfathiazole, and sulfadimethoxine) to determine how chemical structure influences the types of chlorination reactions observed. We conducted free chlorination experiments and developed a non-target approach to extract masses from the experimental dataset that represent the masses of candidate DBPs. Structures were assigned to the candidate DBPs based on analytical data and knowledge of chlorine chemistry. Confidence levels were assigned to each proposed structure according to conventions in the field. In total, 11, 12, and 15 DBP structures were proposed for sulfamethoxazole, sulfathiazole, and sulfadimethoxine, respectively. The structures of the products suggest a variety of reaction types including chlorine substitution, SC cleavage, SN hydrolysis, desulfonation, oxidation/hydroxylation, and conjugation reactions. Some reaction types were common to all of the sulfonamide antibiotics, but unique reaction types were also observed for each sulfonamide antibiotic suggesting that selective prediction of DBP structures of other sulfonamide antibiotics based on chemical structure is unlikely to be possible based on these data alone. This research offers an approach to comprehensively identify DBPs of organic molecules and fills in much needed data on the formation of specific DBPs from three environmentally relevant sulfonamide antibiotics. PMID:27348196

  8. Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity.

    Directory of Open Access Journals (Sweden)

    J R Managbanag

    Full Text Available BACKGROUND: Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein-protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of

  9. A statistical approach for identifying the ionospheric footprint of magnetospheric boundaries from SuperDARN observations

    Directory of Open Access Journals (Sweden)

    G. Lointier

    2008-02-01

    Full Text Available Identifying and tracking the projection of magnetospheric regions on the high-latitude ionosphere is of primary importance for studying the Solar Wind-Magnetosphere-Ionosphere system and for space weather applications. By its unique spatial coverage and temporal resolution, the Super Dual Auroral Radar Network (SuperDARN provides key parameters, such as the Doppler spectral width, which allows the monitoring of the ionospheric footprint of some magnetospheric boundaries in near real-time. In this study, we present the first results of a statistical approach for monitoring these magnetospheric boundaries. The singular value decomposition is used as a data reduction tool to describe the backscattered echoes with a small set of parameters. One of these is strongly correlated with the Doppler spectral width, and can thus be used as a proxy for it. Based on this, we propose a Bayesian classifier for identifying the spectral width boundary, which is classically associated with the Polar Cap boundary. The results are in good agreement with previous studies. Two advantages of the method are: the possibility to apply it in near real-time, and its capacity to select the appropriate threshold level for the boundary detection.

  10. Multi-compartment approach to identify minimal flow and maximal recreational use of a lowland river

    Science.gov (United States)

    Pusch, Martin; Lorenz, Stefan

    2013-04-01

    Most approaches to establish a minimum flow rate for river sections subjected to water abstraction focus on flow requirements of fish and benthic invertebrates. However, artificial reduction of river flow will always affect additional key ecosystem features, as sediment properties and the metabolism of matter in these ecosystems as well, and may even influence adjacent floodplains. Thus, significant effects e.g. on the dissolved oxygen content of river water, on habitat conditions in the benthic zone, and on water levels in the floodplain are to be expected. Thus, we chose a multiple compartment method to identify minimum flow requirements in a lowland River in northern Germany (Spree River), selecting the minimal required flow level out of all compartments studied. Results showed that minimal flow levels necessary to keep key ecosystem features at a 'good' state depended significantly on actual water quality and on river channel morphology. Thereby, water quality of the Spree is potentially influenced by recreational boating activity, which causes mussels to stop filter-feeding, and thus impedes self-purification. Disturbance of mussel feeding was shown to directly depend on boat type and speed, with substantial differences among mussel species. Thus, a maximal recreational boating intensity could be derived that does not significantly affect self purification. We conclude that minimal flow levels should be identified not only based on flow preferences of target species, but also considering channel morphology, ecological functions, and the intensity of other human uses of the river section.

  11. 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.

  12. Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

    Science.gov (United States)

    Versmissen, Jorie; Oosterveer, Daniëlla M; Yazdanpanah, Mojgan; Dehghan, Abbas; Hólm, Hilma; Erdman, Jeanette; Aulchenko, Yurii S; Thorleifsson, Gudmar; Schunkert, Heribert; Huijgen, Roeland; Vongpromek, Ranitha; Uitterlinden, André G; Defesche, Joep C; van Duijn, Cornelia M; Mulder, Monique; Dadd, Tony; Karlsson, Hróbjartur D; Ordovas, Jose; Kindt, Iris; Jarman, Amelia; Hofman, Albert; van Vark-van der Zee, Leonie; Blommesteijn-Touw, Adriana C; Kwekkeboom, Jaap; Liem, Anho H; van der Ouderaa, Frans J; Calandra, Sebastiano; Bertolini, Stefano; Averna, Maurizio; Langslet, Gisle; Ose, Leiv; Ros, Emilio; Almagro, Fátima; de Leeuw, Peter W; Civeira, Fernando; Masana, Luis; Pintó, Xavier; Simoons, Maarten L; Schinkel, Arend FL; Green, Martin R; Zwinderman, Aeilko H; Johnson, Keith J; Schaefer, Arne; Neil, Andrew; Witteman, Jacqueline CM; Humphries, Steve E; Kastelein, John JP; Sijbrands, Eric JG

    2015-01-01

    Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P<1 × 10−4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples. Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics' approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may, therefore, not lead to significant gains in statistical power. PMID:24916650

  13. SU-E-J-212: Identifying Bones From MRI: A Dictionary Learnign and Sparse Regression Approach

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, D; Yang, Y; Cao, M; Hu, P; Low, D [UCLA, Los Angeles, CA (United States)

    2014-06-01

    Purpose: To develop an efficient and robust scheme to identify bony anatomy based on MRI-only simulation images. Methods: MRI offers important soft tissue contrast and functional information, yet its lack of correlation to electron-density has placed it as an auxiliary modality to CT in radiotherapy simulation and adaptation. An effective scheme to identify bony anatomy is an important first step towards MR-only simulation/treatment paradigm and would satisfy most practical purposes. We utilize a UTE acquisition sequence to achieve visibility of the bone. By contrast to manual + bulk or registration-to identify bones, we propose a novel learning-based approach for improved robustness to MR artefacts and environmental changes. Specifically, local information is encoded with MR image patch, and the corresponding label is extracted (during training) from simulation CT aligned to the UTE. Within each class (bone vs. nonbone), an overcomplete dictionary is learned so that typical patches within the proper class can be represented as a sparse combination of the dictionary entries. For testing, an acquired UTE-MRI is divided to patches using a sliding scheme, where each patch is sparsely regressed against both bone and nonbone dictionaries, and subsequently claimed to be associated with the class with the smaller residual. Results: The proposed method has been applied to the pilot site of brain imaging and it has showed general good performance, with dice similarity coefficient of greater than 0.9 in a crossvalidation study using 4 datasets. Importantly, it is robust towards consistent foreign objects (e.g., headset) and the artefacts relates to Gibbs and field heterogeneity. Conclusion: A learning perspective has been developed for inferring bone structures based on UTE MRI. The imaging setting is subject to minimal motion effects and the post-processing is efficient. The improved efficiency and robustness enables a first translation to MR-only routine. The scheme

  14. A novel approach identifying hybrid sterility QTL on the autosomes of Drosophila simulans and D. mauritiana.

    Science.gov (United States)

    Dickman, Christopher T D; Moehring, Amanda J

    2013-01-01

    When species interbreed, the hybrid offspring that are produced are often sterile. If only one hybrid sex is sterile, it is almost always the heterogametic (XY or ZW) sex. Taking this trend into account, the predominant model used to explain the genetic basis of F1 sterility involves a deleterious interaction between recessive sex-linked loci from one species and dominant autosomal loci from the other species. This model is difficult to evaluate, however, as only a handful of loci influencing interspecies hybrid sterility have been identified, and their autosomal genetic interactors have remained elusive. One hindrance to their identification has been the overwhelming effect of the sex chromosome in mapping studies, which could 'mask' the ability to accurately map autosomal factors. Here, we use a novel approach employing attached-X chromosomes to create reciprocal backcross interspecies hybrid males that have a non-recombinant sex chromosome and recombinant autosomes. The heritable variation in phenotype is thus solely caused by differences in the autosomes, thereby allowing us to accurately identify the number and location of autosomal sterility loci. In one direction of backcross, all males were sterile, indicating that sterility could be entirely induced by the sex chromosome complement in these males. In the other direction, we identified nine quantitative trait loci that account for a surprisingly large amount (56%) of the autosome-induced phenotypic variance in sterility, with a large contribution of autosome-autosome epistatic interactions. These loci are capable of acting dominantly, and thus could contribute to F1 hybrid sterility.

  15. An Integrated Multiomics Approach to Identify Candidate Antigens for Serodiagnosis of Human Onchocerciasis.

    Science.gov (United States)

    McNulty, Samantha N; Rosa, Bruce A; Fischer, Peter U; Rumsey, Jeanne M; Erdmann-Gilmore, Petra; Curtis, Kurt C; Specht, Sabine; Townsend, R Reid; Weil, Gary J; Mitreva, Makedonka

    2015-12-01

    Improved diagnostic methods are needed to support ongoing efforts to eliminate onchocerciasis (river blindness). This study used an integrated approach to identify adult female Onchocerca volvulus antigens that can be explored for developing serodiagnostic tests. The first step was to develop a detailed multi-omics database of all O. volvulus proteins deduced from the genome, gene transcription data for different stages of the parasite including eight individual female worms (providing gene expression information for 94.8% of all protein coding genes), and the adult female worm proteome (detecting 2126 proteins). Next, female worm proteins were purified with IgG antibodies from onchocerciasis patients and identified using LC-MS with a high-resolution hybrid quadrupole-time-of-flight mass spectrometer. A total of 241 immunoreactive proteins were identified among those bound by IgG from infected individuals but not IgG from uninfected controls. These included most of the major diagnostic antigens described over the past 25 years plus many new candidates. Proteins of interest were prioritized for further study based on a lack of conservation with orthologs in the human host and other helminthes, their expression pattern across the life cycle, and their consistent expression among individual female worms. Based on these criteria, we selected 33 proteins that should be carried forward for testing as serodiagnostic antigens to supplement existing diagnostic tools. These candidates, together with the extensive pan-omics dataset generated in this study are available to the community (http://nematode.net) to facilitate basic and translational research on onchocerciasis. PMID:26472727

  16. Recommendations for a coordinated approach to regulating the uranium recovery industry

    International Nuclear Information System (INIS)

    A number of regulatory positions that are of central importance to the uranium recovery industry today have their origins in regulatory interpretations that were developed by Nuclear Regulatory Commission (NRC or Commission) staff almost two decades ago, shortly after Congress first granted the Commission the direct authority to regulate uranium mill tailings and related wastes by enacting the Uranium Mill Tailings Radiation Control Act (UMTRCA) as an amendment to the Atomic Energy Act of 1954 (AEA). Consequently, several key regulatory positions that govern uranium recovery activities today were developed at a time when the regulatory programme for uranium milling operations, including the management and disposition of uranium mill tailings and related wastes, was in the earliest stages of conception, and when the uranium recovery industry was at or near peak levels of production. Often, the policies and positions that were developed by the Commission staff dining this period, and subsequently, were developed in an ad hoc manner, rather than being formulated as part of a deliberate, coordinated regulatory strategy. Moreover, many of these positions and policies were based on assumptions that would later turn out to be completely incorrect regarding the future development of the uranium recovery industry and of the regulatory programme governing the industry. In the twenty years that have elapsed since Congress first enacted UMTRCA, a robust programme has been created for the comprehensive regulation of uranium recovery activities. At the same time, the nature of the uranium recovery industry has changed dramatically. As a result, some of the policies and positions that were developed by Commission staff almost two decades ago, that may have seemed reasonable at the time they were developed, appear increasingly unreasonable and inappropriate today, given the current regulatory framework and the realities of the modern uranium recovery industry. This raises concerns

  17. Identifying typical patterns of vulnerability: A 5-step approach based on cluster analysis

    Science.gov (United States)

    Sietz, Diana; Lüdeke, Matthias; Kok, Marcel; Lucas, Paul; Carsten, Walther; Janssen, Peter

    2013-04-01

    Specific processes that shape the vulnerability of socio-ecological systems to climate, market and other stresses derive from diverse background conditions. Within the multitude of vulnerability-creating mechanisms, distinct processes recur in various regions inspiring research on typical patterns of vulnerability. The vulnerability patterns display typical combinations of the natural and socio-economic properties that shape a systems' vulnerability to particular stresses. Based on the identification of a limited number of vulnerability patterns, pattern analysis provides an efficient approach to improving our understanding of vulnerability and decision-making for vulnerability reduction. However, current pattern analyses often miss explicit descriptions of their methods and pay insufficient attention to the validity of their groupings. Therefore, the question arises as to how do we identify typical vulnerability patterns in order to enhance our understanding of a systems' vulnerability to stresses? A cluster-based pattern recognition applied at global and local levels is scrutinised with a focus on an applicable methodology and practicable insights. Taking the example of drylands, this presentation demonstrates the conditions necessary to identify typical vulnerability patterns. They are summarised in five methodological steps comprising the elicitation of relevant cause-effect hypotheses and the quantitative indication of mechanisms as well as an evaluation of robustness, a validation and a ranking of the identified patterns. Reflecting scale-dependent opportunities, a global study is able to support decision-making with insights into the up-scaling of interventions when available funds are limited. In contrast, local investigations encourage an outcome-based validation. This constitutes a crucial step in establishing the credibility of the patterns and hence their suitability for informing extension services and individual decisions. In this respect, working at

  18. A computational approach to identifying gene-microRNA modules in cancer.

    Science.gov (United States)

    Jin, Daeyong; Lee, Hyunju

    2015-01-01

    MicroRNAs (miRNAs) play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patients with the same cancer type, as cancer development is a heterogeneous process. These relationships are more complicated because transcription factors and other regulatory molecules can also regulate miRNAs and genes. Hence, it is important to identify the complex relationships between genes and miRNAs in cancer. In this study, we propose a computational approach to constructing modules that represent these relationships by integrating the expression data of genes and miRNAs with gene-gene interaction data. First, we used a biclustering algorithm to construct modules consisting of a subset of genes and a subset of samples to incorporate the heterogeneity of cancer cells. Second, we combined gene-gene interactions to include genes that play important roles in cancer-related pathways. Then, we selected miRNAs that are closely associated with genes in the modules based on a Gaussian Bayesian network and Bayesian Information Criteria. When we applied our approach to ovarian cancer and glioblastoma (GBM) data sets, 33 and 54 modules were constructed, respectively. In these modules, 91% and 94% of ovarian cancer and GBM modules, respectively, were explained either by direct regulation between genes and miRNAs or by indirect relationships via transcription factors. In addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively, were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively. Finally, we extensively analyzed significant modules and showed that most genes in these modules were related to ovarian cancer and GBM. PMID:25611546

  19. A computational approach to identifying gene-microRNA modules in cancer.

    Directory of Open Access Journals (Sweden)

    Daeyong Jin

    2015-01-01

    Full Text Available MicroRNAs (miRNAs play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patients with the same cancer type, as cancer development is a heterogeneous process. These relationships are more complicated because transcription factors and other regulatory molecules can also regulate miRNAs and genes. Hence, it is important to identify the complex relationships between genes and miRNAs in cancer. In this study, we propose a computational approach to constructing modules that represent these relationships by integrating the expression data of genes and miRNAs with gene-gene interaction data. First, we used a biclustering algorithm to construct modules consisting of a subset of genes and a subset of samples to incorporate the heterogeneity of cancer cells. Second, we combined gene-gene interactions to include genes that play important roles in cancer-related pathways. Then, we selected miRNAs that are closely associated with genes in the modules based on a Gaussian Bayesian network and Bayesian Information Criteria. When we applied our approach to ovarian cancer and glioblastoma (GBM data sets, 33 and 54 modules were constructed, respectively. In these modules, 91% and 94% of ovarian cancer and GBM modules, respectively, were explained either by direct regulation between genes and miRNAs or by indirect relationships via transcription factors. In addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively, were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively. Finally, we extensively analyzed significant modules and showed that most genes in these modules were related to ovarian cancer and GBM.

  20. A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis

    Science.gov (United States)

    Kang, Keunsoo; Bae, Jin-Han; Han, Kyudong; Kim, Eun Soo; Kim, Tae-Oh; Yi, Joo Mi

    2016-01-01

    The cause of inflammatory bowel disease (IBD) is still unknown, but there is growing evidence that environmental factors such as epigenetic changes can contribute to the disease etiology. The aim of this study was to identify newly hypermethylated genes in ulcerative colitis (UC) using a genome-wide DNA methylation approach. Using an Infinium HumanMethylation450 BeadChip array, we screened the DNA methylation changes in three normal colon controls and eight UC patients. Using these methylation profiles, 48 probes associated with CpG promoter methylation showed differential hypermethylation between UC patients and normal controls. Technical validations for methylation analyses in a larger series of UC patients (n = 79) were performed by methylation-specific PCR (MSP) and bisulfite sequencing analysis. We finally found that three genes (FAM217B, KIAA1614 and RIBC2) that were significantly elevating the promoter methylation levels in UC compared to normal controls. Interestingly, we confirmed that three genes were transcriptionally silenced in UC patient samples by qRT-PCR, suggesting that their silencing is correlated with the promoter hypermethylation. Pathway analyses were performed using GO and KEGG databases with differentially hypermethylated genes in UC. Our results highlight that aberrant hypermethylation was identified in UC patients which can be a potential biomarker for detecting UC. Moreover, pathway-enriched hypermethylated genes are possibly implicating important cellular function in the pathogenesis of UC. Overall, this study describes a newly hypermethylated gene panel in UC patients and provides new clinical information that can be used for the diagnosis and therapeutic treatment of IBD. PMID:27517910

  1. A Modeling Approach towards Identifying Potential Bivalent Sensitizers of Neuromuscular Blocking Agents

    Directory of Open Access Journals (Sweden)

    Marc Pudlo

    2016-06-01

    Full Text Available Objective: Anaphylactic reactions induced by neuromuscular blocking agents (NMBAs can occur at first contact and might be due to cross-sensitization by other drugs or chemicals. Our aim was to investigate whether divalent molecules sharing chemical features with NMBAs might potentially cause cross-sensitization. Methods: We constructed a pharmacophore key from chemical features common to all NMBAs (two positive or ionizable features 1.0807 nm apart and used the key to screen FDA-approved small drug molecules of the Drug Bank® database (1541 molecules. The selected molecules were categorized on the basis of the values for three main parameters (fit value, relative energy and mean polar surface area. Results: Screening from the pharmacophore key selected 13 NMBAs and 88 non-NMBA drugs. Of these 88 drugs, 42 had high-ranking parameter values and were considered preferential cross-sensitizers. These included the dopamine D2 receptor ligands aripiprazole and domperidone. Pholcodine, as well as nizatidine, ranitidine, antrafenine, cabergoline and, to some extent, chlorhexidine best fulfilled the required criteria of apolar character, bioavailability and ionization rate. Conclusion: Our data support the hypothesis that pholcodine might be a potential NMBA cross-sensitizer. They confirmed the results of inhibition tests on patient serum suggesting that dopamine D2 receptor ligands might be cross-sensitizers. They also identified chlorhexidine, a widely used disinfectant incriminated in several cases of immediate hypersensitivity reactions, as a potential cross-sensitizer. Pharmacophore modelling is an inexpensive, straightforward approach that can be used to identify potential NMBA cross-sensitizing agents.

  2. An observation-based approach to identify local natural dust events from routine aerosol ground monitoring

    Directory of Open Access Journals (Sweden)

    D. Q. Tong

    2012-02-01

    Full Text Available Dust is a major component of atmospheric aerosols in many parts of the world. Although there exist many routine aerosol monitoring networks, it is often difficult to obtain dust records from these networks, because these monitors are either deployed far away from dust active regions (most likely collocated with dense population or contaminated by anthropogenic sources and other natural sources, such as wildfires and vegetation detritus. Here we propose a new approach to identify local dust events relying solely on aerosol mass and composition from general-purpose aerosol measurements. Through analyzing the chemical and physical characteristics of aerosol observations during satellite-detected dust episodes, we select five indicators to be used to identify local dust records: (1 high PM10 concentrations; (2 low PM2.5/PM10 ratio; (3 higher concentrations and percentage of crustal elements; (4 lower percentage of anthropogenic pollutants; and (5 low enrichment factors of anthropogenic elements. After establishing these identification criteria, we conduct hierarchical cluster analysis for all validated aerosol measurement data over 68 IMPROVE sites in the Western United States. A total of 182 local dust events were identified over 30 of the 68 locations from 2000 to 2007. These locations are either close to the four US Deserts, namely the Great Basin Desert, the Mojave Desert, the Sonoran Desert, and the Chihuahuan Desert, or in the high wind power region (Colorado. During the eight-year study period, the total number of dust events displays an interesting four-year activity cycle (one in 2000–2003 and the other in 2004–2007. The years of 2003, 2002 and 2007 are the three most active dust periods, with 46, 31 and 24 recorded dust events, respectively, while the years of 2000, 2004 and 2005 are the calmest periods, all with single digit dust records. Among these deserts, the Chihuahua Desert (59 cases and the

  3. Mixed Integer Linear Programming based machine learning approach identifies regulators of telomerase in yeast

    Science.gov (United States)

    Poos, Alexandra M.; Maicher, André; Dieckmann, Anna K.; Oswald, Marcus; Eils, Roland; Kupiec, Martin; Luke, Brian; König, Rainer

    2016-01-01

    Understanding telomere length maintenance mechanisms is central in cancer biology as their dysregulation is one of the hallmarks for immortalization of cancer cells. Important for this well-balanced control is the transcriptional regulation of the telomerase genes. We integrated Mixed Integer Linear Programming models into a comparative machine learning based approach to identify regulatory interactions that best explain the discrepancy of telomerase transcript levels in yeast mutants with deleted regulators showing aberrant telomere length, when compared to mutants with normal telomere length. We uncover novel regulators of telomerase expression, several of which affect histone levels or modifications. In particular, our results point to the transcription factors Sum1, Hst1 and Srb2 as being important for the regulation of EST1 transcription, and we validated the effect of Sum1 experimentally. We compiled our machine learning method leading to a user friendly package for R which can straightforwardly be applied to similar problems integrating gene regulator binding information and expression profiles of samples of e.g. different phenotypes, diseases or treatments. PMID:26908654

  4. What influences motivation in Physical Education? A multilevel approach for identifying climate determinants of achievement motivation

    Directory of Open Access Journals (Sweden)

    Benjamin Niederkofler

    2015-03-01

    Full Text Available The present research tested the longitudinal and hierarchical influences of students’ climate perception on the development of achievement motives in Physical Education (PE. Students from Switzerland (N = 919; 45 classes; 50.1% female, age: M = 13.2, SD = 0.6 responded to the questionnaire. Perceived climate was measured using the German LASSO scales (Von Saldern & Littig, 1987, namely teacher care, classmate cooperativeness and satisfaction with teaching. To assess sport specific achievement motives (Hope of Success, HS; Fear of Failure, FF, we used a validated German scale from Elbe, Wenhold, and Müller (2005. Multilevel analysis revealed a link between perceived climate on change of students’ motivation in PE. The investigation also identified factors determining motivation decline caused by the classroom environment and teachers. Moreover, results showed significant gender effects on both motives and a significant impact of individual teacher care on the HS. This was also found for individual and aggregated satisfaction with teaching. The latter was significant for FF on both levels. Interestingly, teacher care showed inhibitory effects on both achievement motives. These findings suggest that students in PE may have unique behaviour which requires a different teaching approach than in normal classroom. This describes a specific learning environment in PE classes. Results are discussed based on students’ unique needs and gender effects.

  5. 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

  6. A Novel Approach for Identifying the Heme—Binding Proteins from Mouse Tissues

    Institute of Scientific and Technical Information of China (English)

    XiaoleiLi; XiaoshanWang; KangZhao; ZhengfengZhou; CaifengZhao; RenYan; LiangLin; TingtingLei; JianningYin; RongWang; ZhongshengSun; ZuyuanXu; JingyueBao; XiugingZhang; XiaoliFeng; SiqiLiu

    2003-01-01

    Heme is a key cofactor in aerobic life,both in eukaryotes and prokaryotes.Because of the high reactivity of ferrous protoporphyrin IX,the reactions of heme in cells are often carried out through heme-protein complexes.Traditionally studies of hemebinding proteins have been approached on a case by case basis,thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues.The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1)purification of heme-binding proteins by hemeagarose,an affinity chromatographic resin;2)isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis;3)identification of heme-binding proteins by mass spectrometry.In five mouse tissues,over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF,in which most proteins belong to heme related.This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.

  7. An approach to identify the novel miRNA encoded from H. Annuus EST sequences.

    Science.gov (United States)

    Gupta, Hemant; Tiwari, Tanushree; Patel, Maulik; Mehta, Aditya; Ghosh, Arpita

    2015-12-01

    MicroRNAs are a newly discovered class of non-protein small RNAs with 22-24 nucleotides. They play multiple roles in biological processes including development, cell proliferation, apoptosis, stress responses and many other cell functions. In this research, several approaches were combined to make a computational prediction of potential miRNAs and their targets in Helianthus annuus (H. annuus). The already available information of the plant miRNAs present in miRBase v21 was used against expressed sequence tags (ESTs). A total of three miRNAs were detected from which one potential novel miRNA was identified following a range of strict filtering criteria. The target prediction was carried out for these three miRNAs having various targets. These targets were functionally annotated and GO terms were assigned. To study the conserved nature of the miRNAs, predicted phylogenetic analysis was carried out. These findings will significantly provide the broader picture for understanding the functions in H. annuus. PMID:26697356

  8. Gene networks associated with conditional fear in mice identified using a systems genetics approach

    Directory of Open Access Journals (Sweden)

    Eskin Eleazar

    2011-03-01

    Full Text Available Abstract Background Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP with high mapping resolution. Results A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance were strongly associated with fear phenotypes. Conclusion Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.

  9. 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.

  10. Machine learning approach identifies new pathways associated with demyelination in a viral model of multiple sclerosis

    Science.gov (United States)

    Ulrich, Reiner; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2010-01-01

    Abstract Theiler’s murine encephalomyelitis is an experimentally virus-induced inflammatory demyelinating disease of the spinal cord, displaying clinical and pathological similarities to chronic progressive multiple sclerosis. The aim of this study was to identify pathways associated with chronic demyelination using an assumption-free combined microarray and immunohistology approach. Movement control as determined by rotarod assay significantly worsened in Theiler’s murine encephalomyelitis -virus-infected SJL/J mice from 42 to 196 days after infection (dpi). In the spinal cords, inflammatory changes were detected 14 to 196 dpi, and demyelination progressively increased from 42 to 196 dpi. Microarray analysis revealed 1001 differentially expressed genes over the study period. The dominating changes as revealed by k-means and functional annotation clustering included up-regulations related to intrathecal antibody production and antigen processing and presentation via major histocompatibility class II molecules. A random forest machine learning algorithm revealed that down-regulated lipid and cholesterol biosynthesis, differentially expressed neurite morphogenesis and up-regulated toll-like receptor-4-induced pathways were intimately associated with demyelination as measured by immunohistology. Conclusively, although transcriptional changes were dominated by the adaptive immune response, the main pathways associated with demyelination included up-regulation of toll-like receptor 4 and down-regulation of cholesterol biosynthesis. Cholesterol biosynthesis is a rate limiting step of myelination and its down-regulation is suggested to be involved in chronic demyelination by an inhibition of remyelination. PMID:19183246

  11. A Novel Approach for Identifying the Heme-Binding Proteins from Mouse Tissues

    Institute of Scientific and Technical Information of China (English)

    Xiaolei Li; Rong Wang; Zhongsheng Sun; Zuyuan Xu; Jingyue Bao; Xiuqing Zhang; Xiaoli Feng; Siqi Liu; Xiaoshan Wang; Kang Zhao; Zhengfeng Zhou; Caifeng Zhao; Ren Yan; Liang Lin; Tingting Lei; Jianning Yin

    2003-01-01

    Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of hemebinding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling hemne-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by hemeagarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.

  12. Integrated Approach to Dense Magnetized Plasmas Applications in Nuclear Fusion Technology. Report of a Coordinated Research Project 2007-2011

    International Nuclear Information System (INIS)

    Through its coordinated research activities, the IAEA promotes the development and application of nuclear technologies in Member States. The scientific and technical knowledge required for the construction and operation of large nuclear fusion research facilities, including ITER and the Laser Megajoule in France, and the Z machine and the National Ignition Facility in the United States of America, necessitates several accompanying research and development programmes in physics and technology. This is particularly true in the areas of materials science and fusion technology. Hence, the long standing IAEA effort to conduct coordinated research projects (CRPs) in these areas is aimed at: (i) the development of appropriate technical tools to investigate the issue of materials damage and degradation in a fusion plasma environment; and (ii) the emergence of a knowledge based understanding of the various processes underlying materials damage and degradation, thereby leading to the identification of suitable candidate materials fulfilling the stringent requirements of a fusion environment in any next step facility. Dense magnetized plasma (DMP) devices serve as a first test bench for testing of fusion relevant plasma facing materials, diagnostic development and calibration, technologies and scaling to conceptual principles of larger devices while sophisticated testing facilities such as the International Fusion Materials Irradiation Facility (IFMIF) are being designed. The CRP on Integrated Approach to Dense Magnetized Plasmas Applications in Nuclear Fusion Technology described herein was initiated in 2007 with the participation of 12 research institutions in 8 Member States and was concluded in 2011. It was designed with specific research objectives falling into two main categories: support to mainstream fusion research and development of DMP technology. This publication is a compilation of the individual reports submitted by the 12 CRP participants. These reports discuss

  13. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

    OpenAIRE

    Jevon Plunkett; Scott Doniger; Guilherme Orabona; Thomas Morgan; Ritva Haataja; Mikko Hallman; Hilkka Puttonen; Ramkumar Menon; Edward Kuczynski; Errol Norwitz; Victoria Snegovskikh; Aarno Palotie; Leena Peltonen; Vineta Fellman; DeFranco, Emily A

    2010-01-01

    Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in par...

  14. Reaction Coordinates and Mechanistic Hypothesis Tests.

    Science.gov (United States)

    Peters, Baron

    2016-05-27

    Reaction coordinates are integral to several classic rate theories that can (a) predict kinetic trends across conditions and homologous reactions, (b) extract activation parameters with a clear physical interpretation from experimental rates, and (c) enable efficient calculations of free energy barriers and rates. New trajectory-based rare events methods can provide rates directly from dynamical trajectories without a reaction coordinate. Trajectory-based frameworks can also generate ideal (but abstract) reaction coordinates such as committors and eigenfunctions of the master equation. However, rates and mechanistic insights obtained from trajectory-based methods and abstract coordinates are not readily generalized across simulation conditions or reaction families. We discuss methods for identifying physically meaningful reaction coordinates, including committor analysis, variational transition state theory, Kramers-Langer-Berezhkovskii-Szabo theory, and statistical inference methods that can use path sampling data to screen, mix, and optimize thousands of trial coordinates. Special focus is given to likelihood maximization and inertial likelihood maximization approaches. PMID:27090846

  15. Reaction Coordinates and Mechanistic Hypothesis Tests.

    Science.gov (United States)

    Peters, Baron

    2016-05-27

    Reaction coordinates are integral to several classic rate theories that can (a) predict kinetic trends across conditions and homologous reactions, (b) extract activation parameters with a clear physical interpretation from experimental rates, and (c) enable efficient calculations of free energy barriers and rates. New trajectory-based rare events methods can provide rates directly from dynamical trajectories without a reaction coordinate. Trajectory-based frameworks can also generate ideal (but abstract) reaction coordinates such as committors and eigenfunctions of the master equation. However, rates and mechanistic insights obtained from trajectory-based methods and abstract coordinates are not readily generalized across simulation conditions or reaction families. We discuss methods for identifying physically meaningful reaction coordinates, including committor analysis, variational transition state theory, Kramers-Langer-Berezhkovskii-Szabo theory, and statistical inference methods that can use path sampling data to screen, mix, and optimize thousands of trial coordinates. Special focus is given to likelihood maximization and inertial likelihood maximization approaches.

  16. Outbreaks source: A new mathematical approach to identify their possible location

    Science.gov (United States)

    Buscema, Massimo; Grossi, Enzo; Breda, Marco; Jefferson, Tom

    2009-11-01

    Classical epidemiology has generally relied on the description and explanation of the occurrence of infectious diseases in relation to time occurrence of events rather than to place of occurrence. In recent times, computer generated dot maps have facilitated the modeling of the spread of infectious epidemic diseases either with classical statistics approaches or with artificial “intelligent systems”. Few attempts, however, have been made so far to identify the origin of the epidemic spread rather than its evolution by mathematical topology methods. We report on the use of a new artificial intelligence method (the H-PST Algorithm) and we compare this new technique with other well known algorithms to identify the source of three examples of infectious disease outbreaks derived from literature. The H-PST algorithm is a new system able to project a distances matrix of points (events) into a bi-dimensional space, with the generation of a new point, named hidden unit. This new hidden unit deforms the original Euclidean space and transforms it into a new space (cognitive space). The cost function of this transformation is the minimization of the differences between the original distance matrix among the assigned points and the distance matrix of the same points projected into the bi-dimensional map (or any different set of constraints). For many reasons we will discuss, the position of the hidden unit shows to target the outbreak source in many epidemics much better than the other classic algorithms specifically targeted for this task. Compared with main algorithms known in the location theory, the hidden unit was within yards of the outbreak source in the first example (the 2007 epidemic of Chikungunya fever in Italy). The hidden unit was located in the river between the two village epicentres of the spread exactly where the index case was living. Equally in the second (the 1967 foot and mouth disease epidemic in England), and the third (1854 London Cholera epidemic

  17. A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.

    Directory of Open Access Journals (Sweden)

    Melissa A Metzler

    Full Text Available The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process.A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a

  18. Identifying diffused nitrate sources in a stream in an agricultural field using a dual isotopic approach.

    Science.gov (United States)

    Ding, Jingtao; Xi, Beidou; Gao, Rutai; He, Liansheng; Liu, Hongliang; Dai, Xuanli; Yu, Yijun

    2014-06-15

    Nitrate (NO3(-)) pollution is a severe problem in aquatic systems in Taihu Lake Basin in China. A dual isotope approach (δ(15)NNO3(-) and δ(18)ONO3(-)) was applied to identify diffused NO3(-) inputs in a stream in an agricultural field at the basin in 2013. The site-specific isotopic characteristics of five NO3(-) sources (atmospheric deposition, AD; NO3(-) derived from soil organic matter nitrification, NS; NO3(-) derived from chemical fertilizer nitrification, NF; groundwater, GW; and manure and sewage, M&S) were identified. NO3(-) concentrations in the stream during the rainy season [mean±standard deviation (SD)=2.5±0.4mg/L] were lower than those during the dry season (mean±SD=4.0±0.5mg/L), whereas the δ(18)ONO3(-) values during the rainy season (mean±SD=+12.3±3.6‰) were higher than those during the dry season (mean±SD=+0.9±1.9‰). Both chemical and isotopic characteristics indicated that mixing with atmospheric NO3(-) resulted in the high δ(18)O values during the rainy season, whereas NS and M&S were the dominant NO3(-) sources during the dry season. A Bayesian model was used to determine the contribution of each NO3(-) source to total stream NO3(-). Results showed that reduced N nitrification in soil zones (including soil organic matter and fertilizer) was the main NO3(-) source throughout the year. M&S contributed more NO3(-) during the dry season (22.4%) than during the rainy season (17.8%). AD generated substantial amounts of NO3(-) in May (18.4%), June (29.8%), and July (24.5%). With the assessment of temporal variation of diffused NO3(-) sources in agricultural field, improved agricultural management practices can be implemented to protect the water resource and avoid further water quality deterioration in Taihu Lake Basin. PMID:24686140

  19. A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells.

    Science.gov (United States)

    Visnyei, Koppany; Onodera, Hideyuki; Damoiseaux, Robert; Saigusa, Kuniyasu; Petrosyan, Syuzanna; De Vries, David; Ferrari, Denise; Saxe, Jonathan; Panosyan, Eduard H; Masterman-Smith, Michael; Mottahedeh, Jack; Bradley, Kenneth A; Huang, Jing; Sabatti, Chiara; Nakano, Ichiro; Kornblum, Harley I

    2011-10-01

    Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells. The paradigm uses a tissue culture model to enrich for GBM stem cells derived from human GBM resections and combines a phenotype-based screen with gene target-specific screens for compound identification. We used 31,624 small molecules from 7 chemical libraries that we characterized and ranked based on their effect on a panel of GBM stem cell-enriched cultures and their effect on the expression of a module of genes whose expression negatively correlates with clinical outcome: MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting differential effects across cell types used, 4 compounds showed selectivity by inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n-palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509 and #5256360 were chosen for more detailed study and inhibited GBM stem cells in self-renewal assays in vitro and in a xenograft model in vivo. These studies show that our screening strategy provides potential candidates and a blueprint for lead compound identification in larger scale screens or screens involving other cancer types. PMID:21859839

  20. An integrative data mining approach to identifying adverse outcome pathway signatures.

    Science.gov (United States)

    Oki, Noffisat O; Edwards, Stephen W

    2016-03-28

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP network with the AHR gene, an interesting subnetwork including glaucoma was identified. While substantial literature exists to support the potential for AHR ligands to elicit glaucoma, it was not explicitly captured in the public annotation information in CTD. The subnetwork from this analysis suggests a cpAOP that includes changes in CYP1B1 expression, which has been previously established in the literature as a primary cause of glaucoma. These case studies highlight the value in integrating multiple data

  1. Predicting Fish Growth Potential and Identifying Water Quality Constraints: A Spatially-Explicit Bioenergetics Approach

    Science.gov (United States)

    Budy, Phaedra; Baker, Matthew; Dahle, Samuel K.

    2011-10-01

    Anthropogenic impairment of water bodies represents a global environmental concern, yet few attempts have successfully linked fish performance to thermal habitat suitability and fewer have distinguished co-varying water quality constraints. We interfaced fish bioenergetics, field measurements, and Thermal Remote Imaging to generate a spatially-explicit, high-resolution surface of fish growth potential, and next employed a structured hypothesis to detect relationships among measures of fish performance and co-varying water quality constraints. Our thermal surface of fish performance captured the amount and spatial-temporal arrangement of thermally-suitable habitat for three focal species in an extremely heterogeneous reservoir, but interpretation of this pattern was initially confounded by seasonal covariation of water residence time and water quality. Subsequent path analysis revealed that in terms of seasonal patterns in growth potential, catfish and walleye responded to temperature, positively and negatively, respectively; crappie and walleye responded to eutrophy (negatively). At the high eutrophy levels observed in this system, some desired fishes appear to suffer from excessive cultural eutrophication within the context of elevated temperatures whereas others appear to be largely unaffected or even enhanced. Our overall findings do not lead to the conclusion that this system is degraded by pollution; however, they do highlight the need to use a sensitive focal species in the process of determining allowable nutrient loading and as integrators of habitat suitability across multiple spatial and temporal scales. We provide an integrated approach useful for quantifying fish growth potential and identifying water quality constraints on fish performance at spatial scales appropriate for whole-system management.

  2. Identifying and Intervening with Substance-Using Women Exposed to Intimate Partner Violence: Phenomenology, Comorbidities, and Integrated Approaches Within Primary Care and Other Agency Settings

    Science.gov (United States)

    Gilbert, Louisa; El-Bassel, Nabila; Resnick, Heidi S.; Noursi, Samia

    2015-01-01

    Abstract Substance use and/or disorders (SUDs) have been identified as a significant correlate of intimate partner violence (IPV) exposure and present complex issues that intersect with the topography of IPV, attendant mental health, and physical co-morbidities and may pose barriers to primary care- and other agency-based screening and intervention efforts. Despite substantial research indicating significantly higher rates of all types and severity of IPV victimization among women with SUDs and bidirectional associations between partner or self-use of drugs or alcohol and IPV victimization, effective screening, brief interventions, coordinated systems of care, and treatment approaches to address these co-occurring problems remain very limited. We integrated select research examining the intersection of IPV victimization and SUDs and several comorbidities that have significant public health impact and provided recommendations for scaling up targeted interventions to redress these co-occurring problems among women in primary, emergency, and other care settings. PMID:25554915

  3. Identifying diffused nitrate sources in a stream in an agricultural field using a dual isotopic approach

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Jingtao [School of Environment, Beijing Normal University, Beijing 100875 (China); Xi, Beidou, E-mail: xbd100012@163.com [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Gao, Rutai; He, Liansheng; Liu, Hongliang [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Dai, Xuanli; Yu, Yijun [Changzhou Environmental Monitoring Center, Jiangsu 213001 (China)

    2014-06-01

    Nitrate (NO{sub 3}{sup −}) pollution is a severe problem in aquatic systems in Taihu Lake Basin in China. A dual isotope approach (δ{sup 15}N-NO{sub 3}{sup −} and δ{sup 18}O-NO{sub 3}{sup −}) was applied to identify diffused NO{sub 3}{sup −} inputs in a stream in an agricultural field at the basin in 2013. The site-specific isotopic characteristics of five NO{sub 3}{sup −} sources (atmospheric deposition, AD; NO{sub 3}{sup −} derived from soil organic matter nitrification, NS; NO{sub 3}{sup −} derived from chemical fertilizer nitrification, NF; groundwater, GW; and manure and sewage, M and S) were identified. NO{sub 3}{sup −} concentrations in the stream during the rainy season [mean ± standard deviation (SD) = 2.5 ± 0.4 mg/L] were lower than those during the dry season (mean ± SD = 4.0 ± 0.5 mg/L), whereas the δ{sup 18}O-NO{sub 3}{sup −} values during the rainy season (mean ± SD = + 12.3 ± 3.6‰) were higher than those during the dry season (mean ± SD = + 0.9 ± 1.9‰). Both chemical and isotopic characteristics indicated that mixing with atmospheric NO{sub 3}{sup −} resulted in the high δ{sup 18}O values during the rainy season, whereas NS and M and S were the dominant NO{sub 3}{sup −} sources during the dry season. A Bayesian model was used to determine the contribution of each NO{sub 3}{sup −} source to total stream NO{sub 3}{sup −}. Results showed that reduced N nitrification in soil zones (including soil organic matter and fertilizer) was the main NO{sub 3}{sup −} source throughout the year. M and S contributed more NO{sub 3}{sup −} during the dry season (22.4%) than during the rainy season (17.8%). AD generated substantial amounts of NO{sub 3}{sup −} in May (18.4%), June (29.8%), and July (24.5%). With the assessment of temporal variation of diffused NO{sub 3}{sup −} sources in agricultural field, improved agricultural management practices can be implemented to protect the water resource and avoid further water

  4. Ground state structure of some double- hypernuclei by a three-body model using a simple coordinate space approach

    Indian Academy of Sciences (India)

    S Mahapatra; J Nag

    2003-06-01

    New experimental data on the binding energy of $^{6}_{}$He, reported very recently, come up with the values = 7.25 ± 0.14 MeV and = 1.01 ± 0.2 MeV which are substantially lower than the old data = 10.9 ± 0.8 MeV and = 4.7 ± 1.0 MeV in use in literature since 1966. In view of the new data we decided to undertake a re-study of the $^{6}_{}$He hypernucleus using the same three-body model (--) with a simple coordinate space variational approach which was employed earlier with the old data on $^{6}_{}$He. After fitting different - potentials to the new data of $^{6}_{}$He we have applied our method to study some double- hypernuclei in light, medium and heavy mass regions and have determined the structural quantities like , the r.m.s. values of core- $(\\langle r_{\\text{core}-}\\rangle)$ and - $(\\langle r_{-}\\rangle)$ distances theoretically. The core- interaction considered is of Woods–Saxon type. The strength and the range of the core- potential have been adjusted to reproduce the -binding energy (). These are in good agreement with the relativistic mean field (RMF) results. Our study shows that the - bonding energy decreases with increasing mass number from $^{10}_{}$Be to $^{210}_{}$Pb of a double- hypernucleus.

  5. Iron(III) carboxylate/aminoalcohol coordination clusters with propeller-shaped Fe8 cores: approaching reasonable exchange energies.

    Science.gov (United States)

    Botezat, Olga; van Leusen, Jan; Kravtsov, Victor Ch; Ellern, Arkady; Kögerler, Paul; Baca, Svetlana G

    2015-12-21

    A series of new octanuclear propeller-like aminoalcohol-supported Fe(III) oxocarboxylate coordination clusters, [Fe8O3(O2CCHMe2)9(tea)(teaH)3]·MeCN·2(H2O) (1), [Fe8O3(O2CCHMe2)6(N3)3(tea)(teaH)3] (2), [Fe8O3(O2CCMe3)6(N3)3(tea)(teaH)3]·0.5(EtOH) (3), and [Fe8O3(O2CCHMe2)6(N3)3(mdea)3(MeO)3] (4) (where teaH3 = triethanolamine; mdeaH2 = N-methyldiethanolamine) has been isolated and magnetochemically analyzed combining the programs wxJFinder and CONDON in an approach to avoid overparameterization issues that are common to larger spin polytopes. Dominant antiferromagnetic exchange interactions exist in all clusters along the edges of the propellers, while moderate ferromagnetic interactions are found along the propeller axes in their {Fe8O3} metallic cores. PMID:26567887

  6. 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

  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. 75 FR 44973 - Report: A New Approach to Targeting Inspection Resources and Identifying Patterns of Adulteration...

    Science.gov (United States)

    2010-07-30

    ... Identifying Patterns of Adulteration: The Reportable Food Registry; Availability AGENCY: Food and Drug... Identifying Patterns of Adulteration: The Reportable Food Registry.'' The report presents FDA's experience... Registry is to help FDA better protect public health by tracking patterns of food and feed adulteration...

  9. Identifying Creatively Gifted Students: Necessity of a Multi-Method Approach

    Science.gov (United States)

    Ambrose, Laura; Machek, Greg R.

    2015-01-01

    The process of identifying students as creatively gifted provides numerous challenges for educators. Although many schools assess for creativity in identifying students for gifted and talented services, the relationship between creativity and giftedness is often not fully understood. This article reviews commonly used methods of creativity…

  10. Key drivers for informal project coordination among sub-contractors

    DEFF Research Database (Denmark)

    Aagaard, Annabeth; Eskerod, Pernille; Madsen, Erik Skov

    2015-01-01

    are massive. Six drivers which enhance informal coordination and three drivers which inhibit informal coordination among sub-contractors in projects were identified. The findings imply that management in project-oriented organizations can enhance informal coordination across project sub......Despite good planning, projects need continuous coordination among the participants concerning scope of work, pace, and timing to be accomplished without delays. Research shows that informal coordination of residual and unforeseen interdependencies enhances time saving and facilitates better...... understandings. Still though, many sub-contractors choose not to coordinate informally. The purpose of this paper is to identify drivers that enhance or inhibits informal coordination in projects. A qualitative, explorative case study approach was applied. Fifteen SME sub-contractors within the offshore wind...

  11. A gene sets approach for identifying prognostic gene signatures for outcome prediction

    OpenAIRE

    Kim Yong Sung; Kim Seon-Young

    2008-01-01

    Abstract Background Gene expression profiling is a promising approach to better estimate patient prognosis; however, there are still unresolved problems, including little overlap among similarly developed gene sets and poor performance of a developed gene set in other datasets. Results We applied a gene sets approach to develop a prognostic gene set from multiple gene expression datasets. By analyzing 12 independent breast cancer gene expression datasets comprising 1,756 tissues with 2,411 pr...

  12. Application of three non-linear econometric approaches to identify business cycles in Peru

    OpenAIRE

    Gabriel Rodríguez

    2010-01-01

    I use three non-linear econometric models to identify and analyze business cycles in the Peruvian economy for the period 1980:1-2008:4. The models are the Smooth Transition Autoregressive (STAR) model suggested by Teräsvirta (1994), the extended version of the Markov-Switching model proposed by Hamilton (1989), and the plucking model of Friedman (1964, 1993). The results indicate strong rejection of the null hypothesis of linearity. The majority of models identify quarters concentrated around...

  13. Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata

    OpenAIRE

    2011-01-01

    Abstract Alopecia areata (AA) is a common hair loss disorder which is thought to be a tissue-specific autoimmune disease. Previous research has identified a few AA susceptibility genes, most of which are implicated in autoimmunity. To identify new genetic variants and further elucidate the genetic basis of AA, we performed a genome-wide association study using the strategy of pooled DNA genotyping (729 cases; 656 controls). The strongest association was for variants in the HLA regi...

  14. A FINANCIAL-ACCOUNTING APPROACH TO PERFORMANCE, IDENTIFYING FINANCIAL KEY COMPONENTS

    OpenAIRE

    TANASA Florentin-Emil; Emil HOROMNEA; UNGUREANU Sebastian

    2012-01-01

    The purpose of this research is the presentation of an accounting and financial perspective on performance by identifying financial components that will facilitate a true and fair view of the target parameter. In this context, the study aims at identifying factors acting on the rate of global financial autonomy to develop relevant decisions on the funding structure of the company. The results show that the assumptions proposed at the level of the analyzed sample, by using quantitative data an...

  15. Mobile Receiver-Assisted Localization Based on Selective Coordinates in Approach to Estimating Proximity for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Zulfazli Hussin

    2014-01-01

    Full Text Available Received signal strength (RSS-based mobile localization has become popular due to its inexpensive localization solutions in large areas. Compared to various physical properties of radio signals, RSS is an attractive approach to localization because it can easily be obtained through existing wireless devices without any additional hardware. Although RSS is not considered to be a good choice for estimating physical distances, it provides some useful distance related information in adding and indicating connectivity information in neighboring nodes. RSS-based localization is generally divided into range-based and rangefree. Range-based localization can achieve excellent accuracy but is too costly to apply to large-scale networks. Methods of range-free localization are regarded as cost-effective solutions for localization in sensor networks. However, the localizations are subject to the effect of radio patterns that affect variations in the radial distance estimates between nodes. It is a challenging task to select an efficient RSS value that can provide small variations in the radial distance in wireless environments. We propose a method of Mobile Localization using the Proximities of Selective coordinates (MoLPS to localize target nodes by using information on proximities between target nodes and mobile receivers as a metric to estimate the location of target nodes. We ran a simulation experiment to assess the performance of MoLPS with 100 target nodes that were randomly deployed along a sensory field boundary. We found from the results of the simulation experiment that localization error had been reduced to below 2m in more than 80% of the target nodes.

  16. A Bayesian approach to identifying structural nonlinearity using free-decay response: Application to damage detection in composites

    Science.gov (United States)

    Nichols, J.M.; Link, W.A.; Murphy, K.D.; Olson, C.C.

    2010-01-01

    This work discusses a Bayesian approach to approximating the distribution of parameters governing nonlinear structural systems. Specifically, we use a Markov Chain Monte Carlo method for sampling the posterior parameter distributions thus producing both point and interval estimates for parameters. The method is first used to identify both linear and nonlinear parameters in a multiple degree-of-freedom structural systems using free-decay vibrations. The approach is then applied to the problem of identifying the location, size, and depth of delamination in a model composite beam. The influence of additive Gaussian noise on the response data is explored with respect to the quality of the resulting parameter estimates.

  17. A care pathway approach to identifying factors that impact on diagnosis of heart disease in British Pakistani women

    OpenAIRE

    Piercy, Hilary; Chowbey, Punita; Soady, John; Dhoot, Parmjeet; Willis, Lerleen; Salway, Sarah

    2012-01-01

    Purpose – The authors examined the cardiac care pathway with the aim of identifying factors that impact on diagnosis and treatment of coronary heart disease in British Pakistani women. Design/methodology/approach – This is an exploratory qualitative study. In depth interviews and focus groups with an opportunistic sample of Pakistani women and a purposive sample of clinicians working at different points along the care pathway were conducted. The authors used a pathways to care approach to ...

  18. Identifying target groups for environmentally sustainable transport: assessment of different segmentation approaches

    DEFF Research Database (Denmark)

    Haustein, Sonja; Hunecke, Marcel

    2013-01-01

    Recently, the use of attitude-based market segmentation to promote environmentally sustainable transport has significantly increased. The segmentation of the population into meaningful groups sharing similar attitudes and preferences provides valuable information about how green measures should b...... and behavioural segmentations are compared regarding marketing criteria. Although none of the different approaches can claim absolute superiority, attitudinal approaches show advantages in providing startingpoints for interventions to reduce car use.......Recently, the use of attitude-based market segmentation to promote environmentally sustainable transport has significantly increased. The segmentation of the population into meaningful groups sharing similar attitudes and preferences provides valuable information about how green measures should...

  19. Development of Novel Random Network Theory-Based Approaches to Identify Network Interactions among Nitrifying Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Cindy

    2015-07-17

    The interactions among different microbial populations in a community could play more important roles in determining ecosystem functioning than species numbers and their abundances, but very little is known about such network interactions at a community level. The goal of this project is to develop novel framework approaches and associated software tools to characterize the network interactions in microbial communities based on high throughput, large scale high-throughput metagenomics data and apply these approaches to understand the impacts of environmental changes (e.g., climate change, contamination) on network interactions among different nitrifying populations and associated microbial communities.

  20. Root productivity of deciduous and evergreen species identified using a molecular approach

    Science.gov (United States)

    Ellsworth, P.; Sternberg, L. O.

    2012-12-01

    The linkage between leaf traits and root structure may explain how plants integrate above and belowground traits into whole plant adaptations to environmental stresses. In dry seasonal forests, the lack of dry season precipitation dries out the relatively nutrient-rich shallow soil, leaving shallow soil water and nutrients inaccessible to uptake until the wet season. In tropical or subtropical seasonal dry forests, deciduousness may allow for the survival of shallow fine roots during the dry season. Losing leaves during the dry season reduces aboveground plant water demand, and a greater proportion of water extracted from deep soil can be used to maintain shallow roots until the wet season. Higher shallow root survival through the dry season than evergreen species means that deciduous species can take advantage of the nutrient pulse associated with the onset of the wet season. To test the above hypothesis, fine roots were collected from soil cores in a seasonally dry forest during the dry season, onset of the wet season, and the wet season and were identified to selected evergreen and deciduous study species. The fine roots of two of the selected species (Lyonia ferruginea and Carya floridana) could be identified from visual characteristics. The other three study species, which were all from the genus Quercus (Q. geminata, Q. myrtifolia, and Q. laevis), were impossible to separate visually. We developed a PCR-based restriction fragment length polymorphism (PCR-RFLP) technique, which provided a quick, simple, low-cost way to identify the species of all fine roots of our study species. We extracted DNA from all roots that were not visually identified, amplified the internal transcribed spacer region (ITS), digested the ITS region with the restriction enzyme TaqαI, and used gel electrophoresis to separate DNA fragments. Using a PCR-RFLP based root identification key that we developed for the species at Archbold Biological Station, all species that could not be

  1. Particle Swarm Based Approach of a Real-Time Discrete Neural Identifier for Linear Induction Motors

    Directory of Open Access Journals (Sweden)

    Alma Y. Alanis

    2013-01-01

    Full Text Available This paper focusses on a discrete-time neural identifier applied to a linear induction motor (LIM model, whose model is assumed to be unknown. This neural identifier is robust in presence of external and internal uncertainties. The proposed scheme is based on a discrete-time recurrent high-order neural network (RHONN trained with a novel algorithm based on extended Kalman filter (EKF and particle swarm optimization (PSO, using an online series-parallel con…figuration. Real-time results are included in order to illustrate the applicability of the proposed scheme.

  2. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    DEFF Research Database (Denmark)

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh;

    2012-01-01

    Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified......, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification...

  3. A Complementary Bioinformatics Approach to Identify Potential Plant Cell Wall Glycosyltransferase-Encoding Genes

    DEFF Research Database (Denmark)

    Egelund, Jack; Skjøt, Michael; Geshi, Naomi;

    2004-01-01

    . Although much is known with regard to composition and fine structures of the plant CW, only a handful of CW biosynthetic GT genes-all classified in the CAZy system-have been characterized. In an effort to identify CW GTs that have not yet been classified in the CAZy database, a simple bioinformatics...

  4. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

    Directory of Open Access Journals (Sweden)

    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  5. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    OpenAIRE

    Deodutta Roy; Marisa Morgan; Changwon Yoo; Alok Deoraj; Sandhya Roy; Vijay Kumar Yadav; Mohannad Garoub; Hamza Assaggaf; Mayur Doke

    2015-01-01

    We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PC...

  6. 78 FR 20672 - Literature Review ApproachIdentifying Research Needs for Assessing Safe Use of High Intakes of...

    Science.gov (United States)

    2013-04-05

    ... program, established in 1978 (43 FR 53060) and headquartered at the NIEHS, whose mission is to evaluate... HUMAN SERVICES National Institutes of Health Literature Review Approach ``Identifying Research Needs for... Assessing Safe Use of High Intakes of Folic Acid,'' for review of the pertinent literature. The document...

  7. A systems biology approach identifies the biochemical mechanisms regulating monoterpenoid essential oil composition in peppermint

    OpenAIRE

    Rios-Estepa, Rigoberto; Turner, Glenn W.; Lee, James M.; Croteau, Rodney B.; Lange, B. Markus

    2008-01-01

    The integration of mathematical modeling and experimental testing is emerging as a powerful approach for improving our understanding of the regulation of metabolic pathways. In this study, we report on the development of a kinetic mathematical model that accurately simulates the developmental patterns of monoterpenoid essential oil accumulation in peppermint (Mentha × piperita). This model was then used to evaluate the biochemical processes underlying experimentally determined changes in the ...

  8. A systems biology approach identifies Molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    OpenAIRE

    Nil Turan; Susana Kalko; Anna Stincone; Kim Clarke; Ayesha Sabah; Katherine Howlett; S John Curnow; Rodriguez, Diego A.; Marta Cascante; Laura O'Neill; Stuart Egginton; Josep Roca; Francesco Falciani

    2011-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular an...

  9. Utilizing Systems Genetics Approaches to Identify Novel Molecular Mechanisms in Cardiovascular Diseases

    OpenAIRE

    Romay, Milagros De La Caridad

    2016-01-01

    Despite the success of focused, reductionist approaches in characterizing the pathophysiology of cardiovascular diseases (CVDs), current estimates predict that 24 million deaths annually will be due to CVDs by 2030. Emphasizing the use of genetic variation in combination with mathematical modeling and integration of next generation –omics profiling technologies, systems genetics characterizes the flow of biological information in physiologic and pathologic states to allow investigators to und...

  10. Astronomy and big data a data clustering approach to identifying uncertain galaxy morphology

    CERN Document Server

    Edwards, Kieran Jay

    2014-01-01

    With the onset of massive cosmological data collection through media such as the Sloan Digital Sky Survey (SDSS), galaxy classification has been accomplished for the most part with the help of citizen science communities like Galaxy Zoo. Seeking the wisdom of the crowd for such Big Data processing has proved extremely beneficial. However, an analysis of one of the Galaxy Zoo morphological classification data sets has shown that a significant majority of all classified galaxies are labelled as “Uncertain”. This book reports on how to use data mining, more specifically clustering, to identify galaxies that the public has shown some degree of uncertainty for as to whether they belong to one morphology type or another. The book shows the importance of transitions between different data mining techniques in an insightful workflow. It demonstrates that Clustering enables to identify discriminating features in the analysed data sets, adopting a novel feature selection algorithms called Incremental Feature Select...

  11. Knowledge-Assisted Approach to Identify Pathways with Differential Dependencies | Office of Cancer Genomics

    Science.gov (United States)

    We have previously developed a statistical method to identify gene sets enriched with condition-specific genetic dependencies. The method constructs gene dependency networks from bootstrapped samples in one condition and computes the divergence between distributions of network likelihood scores from different conditions. It was shown to be capable of sensitive and specific identification of pathways with phenotype-specific dysregulation, i.e., rewiring of dependencies between genes in different conditions.

  12. DiNuP: a systematic approach to identify regions of differential nucleosome positioning

    OpenAIRE

    Fu, Kai; Tang, Qianzi; Feng, Jianxing; Liu, Xiaole Shirley; Zhang, Yong

    2012-01-01

    Motivation: With the rapid development of high-throughput sequencing technologies, the genome-wide profiling of nucleosome positioning has become increasingly affordable. Many future studies will investigate the dynamic behaviour of nucleosome positioning in cells that have different states or that are exposed to different conditions. However, a robust method to effectively identify the regions of differential nucleosome positioning (RDNPs) has not been previously available. Results: We descr...

  13. An International Approach to identify the root causes of Childhood Leukemia

    International Nuclear Information System (INIS)

    Living near a nuclear site is one of the risk factors studied for childhood leukemia. The IRSN and BfS brought together scientists from several disciplines under the aegis of the European Association MelodiGLO to take stock of the existing epidemiological studies, their contributions and their limitations as well as to identify the analysis and research avenues to provide more robust answers. (author)

  14. A Combinatorial Algebraic Approach for the Identifiability of Low-Rank Matrix Completion

    OpenAIRE

    Kiraly, Franz; Tomioka, Ryota

    2012-01-01

    In this paper, we review the problem of matrix completion and expose its intimate relations with algebraic geometry, combinatorics and graph theory. We present the first necessary and sufficient combinatorial conditions for matrices of arbitrary rank to be identifiable from a set of matrix entries, yielding theoretical constraints and new algorithms for the problem of matrix completion. We conclude by algorithmically evaluating the tightness of the given conditions and algorithms for practica...

  15. Identifying patterns in treatment response profiles in acute bipolar mania: a cluster analysis approach

    OpenAIRE

    Houston John P; Lipkovich Ilya A; Ahl Jonna

    2008-01-01

    Abstract Background Patients with acute mania respond differentially to treatment and, in many cases, fail to obtain or sustain symptom remission. The objective of this exploratory analysis was to characterize response in bipolar disorder by identifying groups of patients with similar manic symptom response profiles. Methods Patients (n = 222) were selected from a randomized, double-blind study of treatment with olanzapine or divalproex in bipolar I disorder, manic or mixed episode, with or w...

  16. A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

    Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.

  17. Sequencing-based approach identified three new susceptibility loci for psoriasis.

    Science.gov (United States)

    Sheng, Yujun; Jin, Xin; Xu, Jinhua; Gao, Jinping; Du, Xiaoqing; Duan, Dawei; Li, Bing; Zhao, Jinhua; Zhan, Wenying; Tang, Huayang; Tang, Xianfa; Li, Yang; Cheng, Hui; Zuo, Xianbo; Mei, Junpu; Zhou, Fusheng; Liang, Bo; Chen, Gang; Shen, Changbing; Cui, Hongzhou; Zhang, Xiaoguang; Zhang, Change; Wang, Wenjun; Zheng, Xiaodong; Fan, Xing; Wang, Zaixing; Xiao, Fengli; Cui, Yong; Li, Yingrui; Wang, Jun; Yang, Sen; Xu, Lei; Sun, Liangdan; Zhang, Xuejun

    2014-01-01

    In a previous large-scale exome sequencing analysis for psoriasis, we discovered seven common and low-frequency missense variants within six genes with genome-wide significance. Here we describe an in-depth analysis of noncoding variants based on sequencing data (10,727 cases and 10,582 controls) with replication in an independent cohort of Han Chinese individuals consisting of 4,480 cases and 6,521 controls to identify additional psoriasis susceptibility loci. We confirmed four known psoriasis susceptibility loci (IL12B, IFIH1, ERAP1 and RNF114; 2.30 × 10(-20)≤P≤2.41 × 10(-7)) and identified three new susceptibility loci: 4q24 (NFKB1) at rs1020760 (P=2.19 × 10(-8)), 12p13.3 (CD27-LAG3) at rs758739 (P=4.08 × 10(-8)) and 17q12 (IKZF3) at rs10852936 (P=1.96 × 10(-8)). Two suggestive loci, 3p21.31 and 17q25, are also identified with P<1.00 × 10(-6). The results of this study increase the number of confirmed psoriasis risk loci and provide novel insight into the pathogenesis of psoriasis. PMID:25006012

  18. A proteomic approach to identify proteins from Trichuris trichiura extract with immunomodulatory effects.

    Science.gov (United States)

    Santos, L N; Gallo, M B C; Silva, E S; Figueiredo, C A V; Cooper, P J; Barreto, M L; Loureiro, S; Pontes-de-Carvalho, L C; Alcantara-Neves, N M

    2013-01-01

    Infections with Trichuris trichiura and other trichurid nematodes have been reported to display protective effects against atopy, allergic and autoimmune diseases. The aims of the present study were to investigate the immunomodulatory properties of T. trichiura adult worm extract (TtE) and its fractions (TtEFs) on the production of cytokines by peripheral blood mononuclear cells and to identify their proteinaceous components. Fourteen TtEFs were obtained by ion exchange chromatography and tested for effects on cytokine production by peripheral blood mononuclear cells. The molecular constituents of the six most active fractions were evaluated using nano-LC/mass spectrometry. The homology between T. trichiura and the related nematode Trichinella spiralis was used to identify 12 proteins in TtEFs. Among those identified, fructose biphosphate aldolase, a homologue of macrophage migration inhibitory factor and heat-shock protein 70 may contribute to the immunomodulatory effects of TtEFs. The identification of such proteins could lead to the development of novel drugs for the therapy of allergic and other inflammatory diseases.

  19. Probabilistic approach to identify sensitive parameter distributions in multimedia pathway analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Kamboj, S.; Gnanapragasam, E.; LePoire, D.; Biwer, B. M.; Cheng, J.; Arnish, J.; Yu, C.; Chen, S. Y.; Mo, T.; Abu-Eid, R.; Thaggard, M.; Environmental Assessment; NRC

    2002-01-01

    Sensitive parameter distributions were identified with the use of probabilistic analysis in the RESRAD computer code. RESRAD is a multimedia pathway analysis code designed to evaluate radiological exposures resulting from radiological contamination in soil. The dose distribution was obtained by using a set of default parameter distribution/values. Most of the variations in the output dose distribution could be attributed to uncertainty in a small set of input parameters that could be considered as sensitive parameter distributions. The identification of the sensitive parameters is a first step in the prioritization of future research and information gathering. When site-specific parameter distribution/values are available for an actual site, the same process should be used with these site-specific data. Regression analysis used to identify sensitive parameters indicated that the dominant pathways depended on the radionuclide and source configurations. However, two parameter distributions were sensitive for many radionuclides: the external shielding factor when external exposure was the dominant pathway and the plant transfer factor when plant ingestion was the dominant pathway. No single correlation or regression coefficient can be used alone to identify sensitive parameters in all the cases. The coefficients are useful guides, but they have to be used in conjunction with other aids, such as scatter plots, and should undergo further analysis.

  20. Integration of nuclear spectrometry methods as a new approach to material research. Final report of a coordinated research project 2006-2009

    International Nuclear Information System (INIS)

    In 2006, the IAEA initiated a coordinated research project (CRP) on 'Unification of Nuclear Spectrometries: Integrated Techniques as a New Tool for Material Research' as one of the elements of a project on 'Improvements in Nuclear Spectrometry Applications'. The major objective was to assist laboratories in Member States in enhancing proper utilization of nuclear analytical methods and to help them develop nuclear instruments for special applications. An overall objective of the CRP was to help Member States to improve characterization of materials by the effective utilization of nuclear spectrometry instruments and techniques as well as by developing integrated/unified instruments and analytical methodologies in support of environmental pollution monitoring, industry, study of cultural heritage, human health, agriculture, etc. These techniques can be used in small laboratories as well as in state of the art synchrotron sources. The specific research objectives of the CRP included development (or upgrading) of integrated multifunctional instruments based on nuclear spectrometries and related techniques as well as development of software for the handling and operation of integrated multifunctional instruments, including data acquisition. The CRP also covered: development (or upgrading) of integrated analytical approaches/methodologies and software for processing and presentation of data collected by multifunctional instruments; extension of the applications of integrated/unified instruments; and synergistic and complementary use of nuclear spectrometries, with the aim of assisting end users of nuclear spectrometries in various fields. The CRP covered a period of four years (2006-2009). Twelve laboratories from both developed and developing Member States and the IAEA's Laboratories participated. The first research coordination meeting (RCM) was held in Vienna, from 16 to 20 April 2007. The participants presented progress reports, reviewed the status of the

  1. COMBINATION OF CONVENTIONAL AND IN-SILICO APPROACH FOR IDENTIFYING AN INDUSTRIALLY IMPORTANT ISOLATE OF AEROMONAS

    Directory of Open Access Journals (Sweden)

    Thungri Ghoshal

    2014-01-01

    Full Text Available Ammonia is required for various commercial applications while its production by standard process is immensely energy intense. Dairy industry on the other hand produces huge volume of effluent needing treatment before discharge. This study aims at developing an eco-friendly microbial approach for conversion of dairy industry effluent into ammonia under atmospheric pressure and 37°C temperature at laboratory scale. Thus the need for huge energy for ammonia production would be avoided. Moreover the dairy effluent would generate revenue while getting treated. This study is also an attempt to develop a bioinformatics approach for strain identification. Standard cultivation techniques and in-silico approach of analysis of draft genome was undertaken to decipher the identity of this industrially important strain. Aeromonas sp. MCC 2167 (isolated from active dairy sludge was capable of treating un-amended dairy effluent with 6% inoculum while producing ammonia as by product at a 11 folds higher rate than the modified Habers Process. Though the strain showed maximum identity with Aeromonas hydrophila, there were certain differences in terms of substrate utilization. Majority of the contigs showed identity with Aeromonas hydrophila, however there was significant difference among the two strains in terms of intergenomic distance (genome to genome distance calculator from DSMZ, inversion and frame shift (dot plot analysis as well as genome rearrangement (MAUVE analysis. As per the rapid annotation using subsystem technology analysis 53% of the contigs belong to the subsystem category while the remaining 47% do not match with existing sequences in the database. The above finding proposes bioinformatics validation of the wetlab based data pointing towards this industrially important strain to be a novel isolate of Aeromonas sp. This would lead to an energy efficient economically viable alternative for ammonia production while

  2. A stable isotope approach and its application for identifying nitrate source and transformation process in water.

    Science.gov (United States)

    Xu, Shiguo; Kang, Pingping; Sun, Ya

    2016-01-01

    Nitrate contamination of water is a worldwide environmental problem. Recent studies have demonstrated that the nitrogen (N) and oxygen (O) isotopes of nitrate (NO3(-)) can be used to trace nitrogen dynamics including identifying nitrate sources and nitrogen transformation processes. This paper analyzes the current state of identifying nitrate sources and nitrogen transformation processes using N and O isotopes of nitrate. With regard to nitrate sources, δ(15)N-NO3(-) and δ(18)O-NO3(-) values typically vary between sources, allowing the sources to be isotopically fingerprinted. δ(15)N-NO3(-) is often effective at tracing NO(-)3 sources from areas with different land use. δ(18)O-NO3(-) is more useful to identify NO3(-) from atmospheric sources. Isotopic data can be combined with statistical mixing models to quantify the relative contributions of NO3(-) from multiple delineated sources. With regard to N transformation processes, N and O isotopes of nitrate can be used to decipher the degree of nitrogen transformation by such processes as nitrification, assimilation, and denitrification. In some cases, however, isotopic fractionation may alter the isotopic fingerprint associated with the delineated NO3(-) source(s). This problem may be addressed by combining the N and O isotopic data with other types of, including the concentration of selected conservative elements, e.g., chloride (Cl(-)), boron isotope (δ(11)B), and sulfur isotope (δ(35)S) data. Future studies should focus on improving stable isotope mixing models and furthering our understanding of isotopic fractionation by conducting laboratory and field experiments in different environments.

  3. Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xu-Hua Xu; Yue Huang; Gang Wang; Sheng-Di Chen

    2012-01-01

    Although the pathogenesis of Alzheimer's disease (AD) is still not fully understood,it is acknowledged that intervention should be made at the early stage.Therefore,identifying biomarkers for the clinical diagnosis is critical.Metabolomics,a novel "omics",uses methods based on low-molecular-weight molecules,with high-throughput evaluation of a large number of metabolites that may lead to the identification of new disease-specific biomarkers and the elucidation of pathophysiological mechanisms.This review discusses metabolomics investigations of AD and potential future developments in this field.

  4. Identifying patterns in treatment response profiles in acute bipolar mania: a cluster analysis approach

    Directory of Open Access Journals (Sweden)

    Houston John P

    2008-07-01

    Full Text Available Abstract Background Patients with acute mania respond differentially to treatment and, in many cases, fail to obtain or sustain symptom remission. The objective of this exploratory analysis was to characterize response in bipolar disorder by identifying groups of patients with similar manic symptom response profiles. Methods Patients (n = 222 were selected from a randomized, double-blind study of treatment with olanzapine or divalproex in bipolar I disorder, manic or mixed episode, with or without psychotic features. Hierarchical clustering based on Ward's distance was used to identify groups of patients based on Young-Mania Rating Scale (YMRS total scores at each of 5 assessments over 7 weeks. Logistic regression was used to identify baseline predictors for clusters of interest. Results Four distinct clusters of patients were identified: Cluster 1 (n = 64: patients did not maintain a response (YMRS total scores ≤ 12; Cluster 2 (n = 92: patients responded rapidly (within less than a week and response was maintained; Cluster 3 (n = 36: patients responded rapidly but relapsed soon afterwards (YMRS ≥ 15; Cluster 4 (n = 30: patients responded slowly (≥ 2 weeks and response was maintained. Predictive models using baseline variables found YMRS Item 10 (Appearance, and psychosis to be significant predictors for Clusters 1 and 4 vs. Clusters 2 and 3, but none of the baseline characteristics allowed discriminating between Clusters 1 vs. 4. Experiencing a mixed episode at baseline predicted membership in Clusters 2 and 3 vs. Clusters 1 and 4. Treatment with divalproex, larger number of previous manic episodes, lack of disruptive-aggressive behavior, and more prominent depressive symptoms at baseline were predictors for Cluster 3 vs. 2. Conclusion Distinct treatment response profiles can be predicted by clinical features at baseline. The presence of these features as potential risk factors for relapse in patients who have responded to treatment

  5. Identifying the greatest team and captain - A complex network approach to cricket matches

    OpenAIRE

    Mukherjee, Satyam

    2012-01-01

    We consider all Test matches played between 1877 and 2010 and One Day International (ODI) matches played between 1971 and 2010. We form directed and weighted networks of teams and also of their captains. The success of a team (or captain) is determined by the 'quality' of wins and not on the number of wins alone. We apply the diffusion based PageRank algorithm on the networks to access the importance of wins and rank the teams and captains respectively. Our analysis identifies {\\it Australia}...

  6. Identifying differential expression in multiple SAGE libraries: an overdispersed log-linear model approach

    Directory of Open Access Journals (Sweden)

    Kepler Thomas B

    2005-06-01

    Full Text Available Abstract Background In testing for differential gene expression involving multiple serial analysis of gene expression (SAGE libraries, it is critical to account for both between and within library variation. Several methods have been proposed, including the t test, tw test, and an overdispersed logistic regression approach. The merits of these tests, however, have not been fully evaluated. Questions still remain on whether further improvements can be made. Results In this article, we introduce an overdispersed log-linear model approach to analyzing SAGE; we evaluate and compare its performance with three other tests: the two-sample t test, tw test and another based on overdispersed logistic linear regression. Analysis of simulated and real datasets show that both the log-linear and logistic overdispersion methods generally perform better than the t and tw tests; the log-linear method is further found to have better performance than the logistic method, showing equal or higher statistical power over a range of parameter values and with different data distributions. Conclusion Overdispersed log-linear models provide an attractive and reliable framework for analyzing SAGE experiments involving multiple libraries. For convenience, the implementation of this method is available through a user-friendly web-interface available at http://www.cbcb.duke.edu/sage.

  7. Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents.

    Science.gov (United States)

    Karapetyan, Yervand Eduard; Sferrazza, Gian Franco; Zhou, Minghai; Ottenberg, Gregory; Spicer, Timothy; Chase, Peter; Fallahi, Mohammad; Hodder, Peter; Weissmann, Charles; Lasmézas, Corinne Ida

    2013-04-23

    Prion diseases such as Creutzfeldt-Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases. Because prion protein (PrP) is necessary for prion replication but dispensable for the host, we developed the PrP-FRET-enabled high throughput assay (PrP-FEHTA) to screen for compounds that decrease PrP expression. We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells. Tacrolimus reduced total cellular PrP levels by a nontranscriptional mechanism. Astemizole stimulated autophagy, a hitherto unreported mode of action for this pharmacophore. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice. Astemizole is used in humans to treat seasonal allergic rhinitis in a chronic setting. Given the absence of any treatment option for CJD patients and the favorable drug characteristics of astemizole, including its ability to cross the blood-brain barrier, it may be considered as therapy for CJD patients and for prophylactic use in familial prion diseases. Importantly, our results validate PrP-FEHTA as a method to identify antiprion compounds and, more generally, FEHTA as a unique drug discovery platform. PMID:23576755

  8. A Systematic Approach to Identify Markers of Distinctly Activated Human Macrophages

    Directory of Open Access Journals (Sweden)

    Bayan eSudan

    2015-05-01

    Full Text Available Polarization has been a useful concept for describing activated macrophage phenotypes and gene expression profiles. However, macrophage activation status within tumors and other settings are often inferred based on only a few markers. Complicating matters for relevance to human biology, many of the best studied macrophage activation markers have been best characterized in mice and sometimes are not similarly regulated in human macrophages. To identify novel markers of activated human macrophages, gene expression profiles for human macrophages of a single donor subjected to 33 distinct activating conditions were obtained and a set of putative activation markers were subsequently evaluated in macrophages from multiple donors using integrated fluidic circuit (IFC-based RT-PCR. Using unsupervised hierarchical clustering of the microarray screen, highly-altered transcripts (>4-fold change in expression sorted the macrophage transcription profiles into two major and 13 minor clusters. Among the 1874 highly-altered transcripts, over 100 were uniquely altered in one major or two related minor clusters. IFC PCR-derived data confirmed the microarray results and to show the kinetics of expression of potential macrophage activation markers. Transcripts encoding chemokines, cytokines, and cell surface were prominent in our analyses. The activation markers identified by this study could be used to better characterize tumor-associated macrophages from biopsies as well as other macrophage populations collected from human clinical samples.

  9. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci.

    Science.gov (United States)

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo.

  10. A genomics approach to identify susceptibilities of breast cancer cells to “fever-range” hyperthermia

    International Nuclear Information System (INIS)

    Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed. Bioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells. These data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock

  11. A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity

    Directory of Open Access Journals (Sweden)

    Ana C. D’Alessio

    2015-11-01

    Full Text Available Hundreds of transcription factors (TFs are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.

  12. Identifying the optimal supply temperature in district heating networks - A modelling approach

    DEFF Research Database (Denmark)

    Mohammadi, Soma; Bojesen, Carsten

    2014-01-01

    dynamically while the flow and pressure are calculated on the basis of steady state conditions. The implicit finite element method is applied to simulate the transient temperature behaviour in the network. Pipe network heat losses, pressure drop in the network and return temperature to the plant...... of this study is to develop a model for thermo-hydraulic calculation of low temperature DH system. The modelling is performed with emphasis on transient heat transfer in pipe networks. The pseudo-dynamic approach is adopted to model the District Heating Network [DHN] behaviour which estimates the temperature...... are calculated in the developed model. The model will serve eventually as a basis to find out the optimal supply temperature in an existing DHN in later work. The modelling results are used as decision support for existing DHN; proposing possible modifications to operate at optimal supply temperature....

  13. Identifying Silence Climate in Organizations in the Framework of Contemporary Management Approaches

    Directory of Open Access Journals (Sweden)

    Mustafa Emre Civelek

    2015-12-01

    Full Text Available Dynamic competition conditions in present day bring about the consequence for businesses to face varied problems with each passing day. At this point, current management approaches include studies that would shed light on the new problems of businesses. Organizational Silence, a concept that has recently been being voiced in business world, has come up in such context. Organizational silence could be expressed as the employee behavior of keeping silent about certain negativities due to various reasons in an organization. Since knowledge sharing in modern organizations is of capital importance in terms of responding hastily to the changes in a competitive environment, spread of this behavior of employees to organization culture and climate presents a threat of indifference. In this study, the concept of Organizational Silence is defined and the effects of conceived silence climate on management of organizations are discussed.

  14. Identifying Silence Climate in Organizations in the Framework of Contemporary Management Approaches

    Directory of Open Access Journals (Sweden)

    Mustafa Emre Civelek

    2015-10-01

    Full Text Available Dynamic competition conditions in present day, bring about the consequence for businesses to face varied problems with each passing day. At this point, current management approaches include studies that would shed light on the new problems of businesses. Organizational Silence, a concept that has recently been being voiced in business world, has come up in such context. Organizational silence could be expressed as the employee behavior of keeping silent about certain negativities due to various reasons in an organization. Since knowledge sharing in modern organizations is of capital importance in terms of responding hastily to the changes in a competitive environment, spread of this behavior of employees to organization culture and climate presents a threat of indifference. In this study, the concept of Organizational Silence is defined and the effects of conceived silence climate on management of organizations are discussed.

  15. Pharmacophore-based virtual screening and density functional theory approach to identifying novel butyrylcholinesterase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Sugunadevi SAKKIAH; Keun Woo LEE

    2012-01-01

    Aim:To identify the critical chemical features,with reliable geometric constraints,that contributes to the inhibition of butyrylcholinesterase (BChE) function.Methods:Ligand-based pharmacophore modeling was used to identify the critical chemical features of BChE inhibitors.The generated pharmacophore model was validated using various techniques,such as Fischer's randomization method,test set,and decoy set.The best pharmacophore model was used as a query in virtual screening to identify novel scaffolds that inhibit BChE.Compounds selected by the best hypothesis in the virtual screening were tested for drug-like properties,and molecular docking study was applied to determine the optimal orientation of the hit compounds in the BChE active site.To find the reactivity of the hit compounds,frontier orbital analysis was carried out using density functional theory.Results:Based on its correlation coefficient (0.96),root mean square (RMS) deviation (1.01),and total cost (105.72),the quantitative hypothesis Hypo1 consisting of 2 HBA,1 Hy-Ali,and 1 Hy-Ar was selected as the best hypothesis.Thus,Hypo1 was used as a 3D query in virtual screening of the Maybridge and Chembridge databases.The hit compounds were filtered using ADMET,Lipinski's Rule of Five,and molecular docking to reduce the number of false positive results.Finally,33 compounds were selected based on their critical interactions with the significant amino acids in BChE's active site.To confirm the inhibitors' potencies,the orbital energies,such as HOMO and LUMO,of the hit compounds and 7 training set compounds were calculated.Among the 33 hit compounds,10 compounds with the highest HOMO values were selected,and this set was further culled to 5 compounds based on their energy gaps important for stability and energy transfer.From the overall results,5 hit compounds were confirmed to be potential BChE inhibitors that satisfied all the pharmacophoric features in Hypo1.Conclusion:This study pinpoints important chemical

  16. Identifying dominant controls on hydrologic parameter transfer from gauged to ungauged catchments: a comparative hydrology approach

    Science.gov (United States)

    Singh, R.; Archfield, S.A.; Wagener, T.

    2014-01-01

    Daily streamflow information is critical for solving various hydrologic problems, though observations of continuous streamflow for model calibration are available at only a small fraction of the world’s rivers. One approach to estimate daily streamflow at an ungauged location is to transfer rainfall–runoff model parameters calibrated at a gauged (donor) catchment to an ungauged (receiver) catchment of interest. Central to this approach is the selection of a hydrologically similar donor. No single metric or set of metrics of hydrologic similarity have been demonstrated to consistently select a suitable donor catchment. We design an experiment to diagnose the dominant controls on successful hydrologic model parameter transfer. We calibrate a lumped rainfall–runoff model to 83 stream gauges across the United States. All locations are USGS reference gauges with minimal human influence. Parameter sets from the calibrated models are then transferred to each of the other catchments and the performance of the transferred parameters is assessed. This transfer experiment is carried out both at the scale of the entire US and then for six geographic regions. We use classification and regression tree (CART) analysis to determine the relationship between catchment similarity and performance of transferred parameters. Similarity is defined using physical/climatic catchment characteristics, as well as streamflow response characteristics (signatures such as baseflow index and runoff ratio). Across the entire US, successful parameter transfer is governed by similarity in elevation and climate, and high similarity in streamflow signatures. Controls vary for different geographic regions though. Geology followed by drainage, topography and climate constitute the dominant similarity metrics in forested eastern mountains and plateaus, whereas agricultural land use relates most strongly with successful parameter transfer in the humid plains.

  17. Identifying dominant controls on hydrologic parameter transfer from gauged to ungauged catchments - A comparative hydrology approach

    Science.gov (United States)

    Singh, R.; Archfield, S. A.; Wagener, T.

    2014-09-01

    Daily streamflow information is critical for solving various hydrologic problems, though observations of continuous streamflow for model calibration are available at only a small fraction of the world's rivers. One approach to estimate daily streamflow at an ungauged location is to transfer rainfall-runoff model parameters calibrated at a gauged (donor) catchment to an ungauged (receiver) catchment of interest. Central to this approach is the selection of a hydrologically similar donor. No single metric or set of metrics of hydrologic similarity have been demonstrated to consistently select a suitable donor catchment. We design an experiment to diagnose the dominant controls on successful hydrologic model parameter transfer. We calibrate a lumped rainfall-runoff model to 83 stream gauges across the United States. All locations are USGS reference gauges with minimal human influence. Parameter sets from the calibrated models are then transferred to each of the other catchments and the performance of the transferred parameters is assessed. This transfer experiment is carried out both at the scale of the entire US and then for six geographic regions. We use classification and regression tree (CART) analysis to determine the relationship between catchment similarity and performance of transferred parameters. Similarity is defined using physical/climatic catchment characteristics, as well as streamflow response characteristics (signatures such as baseflow index and runoff ratio). Across the entire US, successful parameter transfer is governed by similarity in elevation and climate, and high similarity in streamflow signatures. Controls vary for different geographic regions though. Geology followed by drainage, topography and climate constitute the dominant similarity metrics in forested eastern mountains and plateaus, whereas agricultural land use relates most strongly with successful parameter transfer in the humid plains.

  18. Problematic severe asthma: a proposed approach to identifying children who are severely resistant to therapy.

    Science.gov (United States)

    Konradsen, Jon R; Nordlund, Björn; Lidegran, Marika; Pedroletti, Christophe; Grönlund, Hans; van Hage, Marianne; Dahlen, Barbro; Hedlin, Gunilla

    2011-02-01

    Children with problematic severe asthma (PA) are either difficult to treat because of the presence of aggravating factors or else severely resistant to therapy. We investigated a cohort of school-aged children with PA and compared these children to age-matched peers with controlled persistent asthma (CA). The aims were to characterize features of children suffering from PA and identify children who were severely resistant to therapy. In this cross-sectional, multicenter comparison of children with different manifestations of persistent asthma, PA was defined as insufficient asthma control despite level 4 treatment, according to GINA. The protocol included questionnaires, spirometry, methacholine provocation, measurement of fraction of nitric oxide in exhaled (FE(NO) ) and nasal air, blood sampling for inflammatory biomarkers and atopy, and computerized tomography of sinuses and lungs (in the PA group only). Of the 54 children with PA, 61% had therapy-resistant asthma, with the remaining being difficult to treat because of identified aggravating factors. Children with PA more often had parents with asthma (p=0.003), came from families with a lower socioeconomic status (p=0.01), were less physically active (p=0.04), and had more comorbidity with rhinoconjunctivitis (p=0.01) than did the 39 children with CA. The former also exhibited lower FEV(1) values (p=0.02) and increased bronchial hyper-responsiveness (p=0.01), but there were no differences in atopy (p=0.81) or FE(NO) (p=0.16). A non-invasive protocol, involving a standardized and detailed clinical characterization, revealed distinguishing features of children with PA and enabled the identification of children with therapy-resistant asthma. PMID:20880352

  19. One Health approach to identify research needs in bovine and human babesioses: workshop report

    Directory of Open Access Journals (Sweden)

    McElwain Terry F

    2010-04-01

    Full Text Available Abstract Background Babesia are emerging health threats to humans and animals in the United States. A collaborative effort of multiple disciplines to attain optimal health for people, animals and our environment, otherwise known as the One Health concept, was taken during a research workshop held in April 2009 to identify gaps in scientific knowledge regarding babesioses. The impetus for this analysis was the increased risk for outbreaks of bovine babesiosis, also known as Texas cattle fever, associated with the re-infestation of the U.S. by cattle fever ticks. Results The involvement of wildlife in the ecology of cattle fever ticks jeopardizes the ability of state and federal agencies to keep the national herd free of Texas cattle fever. Similarly, there has been a progressive increase in the number of cases of human babesiosis over the past 25 years due to an increase in the white-tailed deer population. Human babesiosis due to cattle-associated Babesia divergens and Babesia divergens-like organisms have begun to appear in residents of the United States. Research needs for human and bovine babesioses were identified and are presented herein. Conclusions The translation of this research is expected to provide veterinary and public health systems with the tools to mitigate the impact of bovine and human babesioses. However, economic, political, and social commitments are urgently required, including increased national funding for animal and human Babesia research, to prevent the re-establishment of cattle fever ticks and the increasing problem of human babesiosis in the United States.

  20. Verbal Self-Guidance as a Treatment Approach for Children with Developmental Coordination Disorder: A Systematic Replication Study.

    Science.gov (United States)

    Martini, Rose; Polatajko, Helene J.

    1998-01-01

    Replicating a 1994 study, four children with developmental coordination disorder (DCD) were taught a verbal self-guidance strategy (Goal, Plan, Do, Check) by an occupational therapist. All four improved performance in attaining their occupational goals, supporting the possible use of a cognitive strategy with children with DCD. (SK)

  1. Development and validation of a novel approach to the calibration of internal and external threads on coordinate measuring machines

    DEFF Research Database (Denmark)

    Carmignato, Simone; De Chiffre, Leonardo; Savio, Enrico;

    The paper reports on the development and validation of a new experimental method for the traceable measurement of threads on coordinate measuring machines. The calibration procedure involves scanning of thread profiles using a needle-like probe, extracting all the main parameters of the thread ge...

  2. Managing Coordinator, Educational or Entrepreneurial Coordinator: Course Coordinator Profile Analysis at Private HEIS

    Directory of Open Access Journals (Sweden)

    Mariana Augusta de Araújo Silva

    2014-12-01

    Full Text Available Higher Education dynamics is impacted by political, economic and financial interference. In parallel, the Ministry of Education and Culture (MEC is strict in its reviews to ensure Brazilian higher education is appreciated and promoted. The purpose of this study is to identify the profile of Course Coordinators and factors that might improve, at the surveyed HEIs, this professional´s relationship with students, teaching staff and Directors. Literature was searched and reviewed so as to collect subject matter pertaining issues. A quantitative research approach was employed and objectives were of exploratory descriptive nature since this technique ensures extended comprehension of the investigated phenomenon, whilst data was gathered via personal interviews. The object of investigation comprised all Course Coordinators of the Estácio/Natal Group in Brazil´s four units. The survey´s tool comprises: 13 closed questions to identify the Coordinator´s profile; 17 questions with a 5 point Likert score scale to identify the entrepreneurial profile; 42 also resorting to a 5 point Likert score scale to measure the dimensions of the Coordinator´s activities and 4 open, optional questions to measure difficulties and possibilities that impact the development of an entrepreneurial course management approach. The study employed both a statistical method (data analysis and descriptive statistics. Findings lead to the conclusion that information and knowledge gathered support researched HEIs in their overcoming of challenges, amongst which encouraging strategic course management and innovation, focused on implementing a new vision of the Course Coordinator, as professionals that master how to balance management and pedagogical skills, whilst innovating by resorting to entrepreneurial competencies.

  3. Coordination of the cortisol and testosterone responses: A dual axis approach to understanding the response to social status threats.

    Science.gov (United States)

    Turan, Bulent; Tackett, Jennifer L; Lechtreck, Maria T; Browning, Wesley R

    2015-12-01

    For many people, competitions, status challenges, and being evaluated by others result in increases in cortisol as well as testosterone. It is argued that physiological processes work in a coordinated fashion when facing social evaluative-competitive situations. Such a coordinated response may be part of an evolved system, monitoring and responding to threats to one's social status. In two studies, using within-person multi-level analyses, we tested the hypothesis that adult men, pre/early pubertal boys, and pre/early pubertal girls show a coordinated response in cortisol and testosterone (i.e., coupling of cortisol and testosterone responses) during a social evaluative situation. In Study 1, 85 men delivered speeches and performed difficult arithmetic tasks in front of critical evaluators, prepared for a competition, and provided multiple saliva samples throughout the procedure for cortisol and testosterone assays. In Study 2, 79 boys and 74 girls underwent similar procedures as in Study 1. Within-person analyses suggested that cortisol and testosterone responses were indeed positively associated for all three groups (men, boys, and girls). That is, on average a participant's cortisol and testosterone levels tended to rise and fall together throughout the procedure, suggesting that cortisol and testosterone show coordinated activation and deactivation (coupling) during social status threats. Furthermore, men with higher anxiety during the stressor tasks (Study 1; coded by raters from video recordings) and both boys and girls with higher parent reported trait negative affectivity (Study 2) had stronger coupling. Men (Study 1) higher in self-reported trait dominance and verbal dominance (coded by raters from video recordings during the stressor), and lower in basal testosterone had weaker coupling. A coordinated hormone response may have important adaptive functions when dealing with status threats; cortisol can mobilize energy resources and testosterone can

  4. Identifying student resources in reasoning about entropy and the approach to thermal equilibrium

    Science.gov (United States)

    Loverude, Michael

    2015-12-01

    [This paper is part of the Focused Collection on Upper Division Physics Courses.] As part of an ongoing project to examine student learning in upper-division courses in thermal and statistical physics, we have examined student reasoning about entropy and the second law of thermodynamics. We have examined reasoning in terms of heat transfer, entropy maximization, and statistical treatments of multiplicity and probability. In this paper, we describe student responses in interviews focused on the approach of macroscopic systems to thermal equilibrium. Our data suggest that students do not use a single simple model of entropy, but rather use a variety of conceptual resources. Individual students frequently shifted between resources, in some cases leading to contradictory predictions. Among the resources that students employed were some that have been previously described in the literature, including inappropriate use of conservation. However, our results suggest that student use of resources connected to disorder are neither simple nor monolithic. For example, many students used a previously unreported association between the equilibrium state of a system and an increase in order, rather than disorder.

  5. Multi-omics approach identifies molecular mechanisms of plant-fungus mycorrhizal interaction

    Directory of Open Access Journals (Sweden)

    Peter E Larsen

    2016-01-01

    Full Text Available In mycorrhizal symbiosis, plant roots form close, mutually beneficial interactions with soil fungi. Before this mycorrhizal interaction can be established however, plant roots must be capable of detecting potential beneficial fungal partners and initiating the gene expression patterns necessary to begin symbiosis. To predict a plant root – mycorrhizal fungi sensor systems, we analyzed in vitro experiments of Populus tremuloides (aspen tree and Laccaria bicolor (mycorrhizal fungi interaction and leveraged over 200 previously published transcriptomic experimental data sets, 159 experimentally validated plant transcription factor binding motifs, and more than 120-thousand experimentally validated protein-protein interactions to generate models of pre-mycorrhizal sensor systems in aspen root. These sensor mechanisms link extracellular signaling molecules with gene regulation through a network comprised of membrane receptors, signal cascade proteins, transcription factors, and transcription factor biding DNA motifs. Modeling predicted four pre-mycorrhizal sensor complexes in aspen that interact with fifteen transcription factors to regulate the expression of 1184 genes in response to extracellular signals synthesized by Laccaria. Predicted extracellular signaling molecules include common signaling molecules such as phenylpropanoids, salicylate, and, jasmonic acid. This multi-omic computational modeling approach for predicting the complex sensory networks yielded specific, testable biological hypotheses for mycorrhizal interaction signaling compounds, sensor complexes, and mechanisms of gene regulation.

  6. Biomechanical approaches to identify and quantify injury mechanisms and risk factors in women's artistic gymnastics.

    Science.gov (United States)

    Bradshaw, Elizabeth J; Hume, Patria A

    2012-09-01

    Targeted injury prevention strategies, based on biomechanical analyses, have the potential to help reduce the incidence and severity of gymnastics injuries. This review outlines the potential benefits of biomechanics research to contribute to injury prevention strategies for women's artistic gymnastics by identification of mechanisms of injury and quantification of the effects of injury risk factors. One hundred and twenty-three articles were retained for review after searching electronic databases using key words, including 'gymnastic', 'biomech*', and 'inj*', and delimiting by language and relevance to the paper aim. Impact load can be measured biomechanically by the use of instrumented equipment (e.g. beatboard), instrumentation on the gymnast (accelerometers), or by landings on force plates. We need further information on injury mechanisms and risk factors in gymnastics and practical methods of monitoring training loads. We have not yet shown, beyond a theoretical approach, how biomechanical analysis of gymnastics can help reduce injury risk through injury prevention interventions. Given the high magnitude of impact load, both acute and accumulative, coaches should monitor impact loads per training session, taking into consideration training quality and quantity such as the control of rotation and the height from which the landings are executed. PMID:23072044

  7. Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

    Science.gov (United States)

    Pierce, Christopher G.; Lopez-Ribot, Jose L.

    2014-01-01

    Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751

  8. A harmonised approach for identifying core foods for total diet studies.

    Science.gov (United States)

    Devlin, Niamh F C; McNulty, Breige A; Turrini, Aida; Tlustos, Christina; Hearty, Aine P; Volatier, Jean-Luc; Kelleher, Cecily C; Nugent, Anne P

    2014-01-01

    Total diet studies (TDS) are used to gather information on chemical substances in food, thereby facilitating risk assessments and health monitoring. Candidate foods for inclusion in a TDS should represent a large part of a typical diet to estimate accurately the exposure of a population and/or specific population groups. There are currently no harmonised guidelines for the selection of foods in a TDS, and so the aim of this study was to explore the possibility of generating a harmonised approach to be used across Europe. Summary statistics data from the European Food Safety Authority's (EFSA) Comprehensive Food Consumption Database were used in this research, which provided data from national food consumption surveys in Europe. The chosen methodology for the selection of foods was based on the weight of food consumed and consumer rate. Using the available data, 59 TDS food lists were created, representing over 51 000 people across 17 countries and seven population groups. All TDS food lists represented > 85% of the populations' diets (85.9-96.3%), while the number of foods in the TDS food lists ranged from 15 to 102. Comparison of the TDS food lists indicated that the most commonly consumed foods included wheat bread and rolls, pastries and cakes, tomatoes, apples, bananas, and chicken, while cow's milk, tap water and orange juice were the most commonly consumed beverages across Europe. This work was complete to support EFSA and other institutions in the development of harmonised TDS into the future. PMID:24893144

  9. A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States

    Directory of Open Access Journals (Sweden)

    Dufault Renee

    2012-04-01

    Full Text Available Abstract The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91% between 2005 to 2010 while the number of children receiving special education services overall declined by 5%. The demand for special education services continues to rise in disability categories associated with pervasive developmental disorders. Neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors, such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as mercury or organophosphate pesticides. Gene expression patterns differ geographically between populations and within populations. Gene variants of paraoxonase-1 are associated with autism in North America, but not in Italy, indicating regional specificity in gene-environment interactions. In the current review, we utilize a novel macroepigenetic approach to compare variations in diet and toxic substance exposure between these two geographical populations to determine the likely factors responsible for the autism epidemic in the United States.

  10. Identifying Microphone from Noisy Recordings by Using Representative Instance One Class-Classification Approach

    Directory of Open Access Journals (Sweden)

    Huy Quan Vu

    2012-06-01

    Full Text Available Rapid growth of technical developments has created huge challenges for microphone forensics - a sub-category of audio forensic science, because of the availability of numerous digital recording devices and massive amount of recording data. Demand for fast and efficient methods to assure integrity and authenticity of information is becoming more and more important in criminal investigation nowadays. Machine learning has emerged as an important technique to support audio analysis processes of microphone forensic practitioners. However, its application to real life situations using supervised learning is still facing great challenges due to expensiveness in collecting data and updating system. In this paper, we introduce a new machine learning approach which is called One-class Classification (OCC to be applied to microphone forensics; we demonstrate its capability on a corpus of audio samples collected from several microphones. In addition, we propose a representative instance classification framework (RICF that can effectively improve performance of OCC algorithms for recording signal with noise. Experiment results and analysis indicate that OCC has the potential to benefit microphone forensic practitioners in developing new tools and techniques for effective and efficient analysis.

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

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    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.

  12. IDENTIFYING THE INDUSTRY BUSINESS CYCLE USING THE MARKOV SWITCHING APPROACH IN CENTRAL AND EASTERN EUROPE

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    Cristi SPULBĂR

    2012-01-01

    Full Text Available In this article we use a Markov Switching model with two lags to identify and to compare the business cycle in Romania, Czech Republic, Hungary and Poland using data on industrial production for the 1991-2011 period. We use a model with two regimes that reflect the economic expansions and contractions. The Markov Switching models have been widely used in order to detect and to date the business cycle turning points. However, it should be pointed out that the industrial production may have a little bit different dynamics than the quarterly gross domestic product which is the main measure of economic activity. Based on the smoothed regime probabilities the model track three recessionary periods of the Romanian economy in 1991, 1997 and 2009 and two recessionary periods for the other countries in 1991 and 2009. Mean yoy growth of IPI is 5.01% during expansion periods, while it switches to -18.6% during contraction periods for the Romanian economy. In comparison, mean yoy growth of IPI is 7.25% during expansion periods, while it switches to -13.4% during contraction periods for the Poland economy. Furthermore, in Romania, the duration of the three recessions in months was 25, 25 and 9 months. In Poland, the duration of the two recessions was 16 and 10 months. The results of the study may be used in order to compare the business cycle in Central and Eastern European countries with the Euro Area business cycle.

  13. An improved approach to identify irradiated spices using electronic nose, FTIR, and EPR spectroscopy.

    Science.gov (United States)

    Sanyal, Bhaskar; Ahn, Jae-Jun; Maeng, Jeong-Hwan; Kyung, Hyun-Kyu; Lim, Ha-Kyeong; Sharma, Arun; Kwon, Joong-Ho

    2014-09-01

    Changes in cumin and chili powder from India resulting from electron-beam irradiation were investigated using 3 analytical methods: electronic nose (E-nose), Fourier transform infrared (FTIR) spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. The spices had been exposed to 6 to 14 kGy doses recommended for microbial decontamination. E-nose measured a clear difference in flavor patterns of the irradiated spices in comparison with the nonirradiated samples. Principal component analysis further showed a dose-dependent variation. FTIR spectra of the samples showed strong absorption bands at 3425, 3007 to 2854, and 1746 cm(-1). However, both nonirradiated and irradiated spice samples had comparable patterns without any noteworthy changes in functional groups. EPR spectroscopy of the irradiated samples showed a radiation-specific triplet signal at g = 2.006 with a hyper-fine coupling constant of 3 mT confirming the results obtained with the E-nose technique. Thus, E-nose was found to be a potential tool to identify irradiated spices.

  14. A Neural Network Approach for Identifying Relativistic Electron Pitch Angle Distributions in Van Allen Probes Data

    Science.gov (United States)

    Souza, V. M. C. E. S.; Vieira, L.; Alves, L. R.; Da Silva, L. A.; Koga, D.; Sibeck, D. G.; Walsh, B.; Kanekal, S. G.; Silveira, M. D.; Medeiros, C.; Mendes, O., Jr.; Marchezi, J.; Rockenbach, M.; Jauer, P. R.; Gonzalez, W.; Baker, D. N.

    2015-12-01

    A myriad of physical phenomena occur in the inner magnetosphere, in particular at the Earth's radiation belts, which can be a result of the combination of both internal and external processes. However, the connection between physical processes occurring deep within the magnetosphere and external interplanetary drivers it is not yet well understood. In this work we investigate whether a selected set of interplanetary structures affect the local time distribution of three different classes of high energy electron pitch angle distributions (PADs), namely normal, isotropic, and butterfly. We split this work into two parts: initially we focus on the methodology used which employs a Self-Organized Feature Map (SOFM) neural network for identifying different classes of electron PAD shapes in the Van Allen Probes' Relativistic Electron Proton Telescope (REPT) data. The algorithm can categorize the input data into an arbitrary number of classes from which three of them appears the most: normal, isotropic and butterfly. Other classes which are related with these three also emerge and deserve to be addressed in detail in future works. We also discuss the uncertainties of the algorithm. Then, we move to the second part where we describe in details the criteria used for selecting the interplanetary events, and also try to investigate the relation between key parameters characterizing such interplanetary structures and the local time distributions of electron PAD shapes.

  15. Identifying differences in the experience of (in)authenticity: a latent class analysis approach.

    Science.gov (United States)

    Lenton, Alison P; Slabu, Letitia; Bruder, Martin; Sedikides, Constantine

    2014-01-01

    Generally, psychologists consider state authenticity - that is, the subjective sense of being one's true self - to be a unitary and unidimensional construct, such that (a) the phenomenological experience of authenticity is thought to be similar no matter its trigger, and (b) inauthenticity is thought to be simply the opposing pole (on the same underlying construct) of authenticity. Using latent class analysis, we put this conceptualization to a test. In order to avoid over-reliance on a Western conceptualization of authenticity, we used a cross-cultural sample (N = 543), comprising participants from Western, South-Asian, East-Asian, and South-East Asian cultures. Participants provided either a narrative in which the described when they felt most like being themselves or one in which they described when they felt least like being themselves. The analysis identified six distinct classes of experiences: two authenticity classes ("everyday" and "extraordinary"), three inauthenticity classes ("self-conscious," "deflated," and "extraordinary"), and a class representing convergence between authenticity and inauthenticity. The classes were phenomenologically distinct, especially with respect to negative affect, private and public self-consciousness, and self-esteem. Furthermore, relatively more interdependent cultures were less likely to report experiences of extraordinary (in)authenticity than relatively more independent cultures. Understanding the many facets of (in)authenticity may enable researchers to connect different findings and explain why the attainment of authenticity can be difficult.

  16. A Genetic Algorithm Based Approach for Segmentingand Identifying Defects in Glass Bottles

    Directory of Open Access Journals (Sweden)

    George Mathew

    2016-07-01

    Full Text Available This work mainly aims at designing and developing a suitable tool for identifying defects in glass bottles through visual inspection based on Segmentation algorithm. The defect identification is done in three stages. These are Image acquisition, Pre-processing and filtering and Segmentation. In the Image acquisition stage, samples of real time images are taken and are converted into 512x512 monochrome images. In the Preprocessing and filtering stage, the image acquired is passed through median filters. The Proposed filter is Modified Decision Based Unsymmetric Trimmed Median Filter (MDBUTMF because it produces a high value of Peak to Signal Ratio (PSNR of 60-75db.The de-noised images is further sent to the third stage which is Segmentation. In this work, Segmentation is done using Genetic Algorithm (GA. The defects in the images are segmented and highlighted. Thus the areas of defects are spotted out. The Genetic segmentation has produced high Sensitivity, high Specificity and high Accuracy of 92%, 93% and 93% respectively. Thus the Proposed work produced effective results and hence this tool shall be useful for food processing industries for the Quality Inspection of the glass bottles

  17. Analytical approaches to identify potential migrants in polyester-polyurethane can coatings.

    Science.gov (United States)

    Louise Bradley, Emma; Driffield, Malcolm; Guthrie, James; Harmer, Nick; Thomas Oldring, Peter Kenneth; Castle, Laurence

    2009-12-01

    The safety of a polyester-polyurethane can coating has been assessed using a suite of complementary analytical methods to identify and estimate the concentrations of potential chemical migrants. The polyester was based on phthalic acids and aliphatic diols. The polyisocyanate cross-linking agent was 1-isocyanato-3-isocyanatomethyl-3,5,5-trimethyl cyclohexane homopolymer (IPDI) blocked with methylethylketone oxime (MEKO) to make a one-part formulation. The overall migrate, obtained using solvent extraction of cured films, comprised almost completely of 12 cyclic and one linear polyester oligomer up to molecular weight 800 and containing up to six monomer units. These 13 oligomers covered a total of 28 isomeric forms. Other minor components detected were plasticisers and surfactants as well as impurities present in the starting materials. There was no detectable residue of either the blocked isocyanate (<0.01 microg/dm(2)) used as the starting substance or the unblocked isocyanate (<0.02 microg/dm(2)). The level of extractable IPDI was used as an indicator of the completeness of cure in experimental coatings. These studies revealed that there was an influence of time, temperature and catalyst content. Polymerisation was also influenced by the additives used and by the ageing of the wet coating formulation over several months. These studies allow parameters to be specified to ensure that commercial production coatings receive a full cure giving low migration characteristics.

  18. A metabolomics approach to identify and quantify the phytochemicals in watermelons by quantitative (1)HNMR.

    Science.gov (United States)

    Jayaprakasha, G K; Patil, Bhimanagouda S

    2016-06-01

    Watermelon (Citrullus vulgaris) contains many health-promoting compounds, such as ascorbic acid, carotenoids, phenolic acids and amino acids including l-citrulline, arginine, and glutathione. Reported HPLC method for quantification of l-citrulline and sugars in watermelon involves, time-consuming sample preparation, post-column color development and detection with fluorescence and refractive index detectors. The present study describes development of a method to identify and quantify amino acids and sugars simultaneously from watermelon samples using quantitative proton NMR. Lyophilized watermelon samples (30-50mg) were extracted with deuterium oxide (D2O) by sonication and the centrifuged extract was directly used for quantification and identification with (1)HNMR. An external coaxial insert containing a 65µL of 0.012% 3-(trimethylsilyl) propionic-(2,2,3,3-d4) acid sodium salt (TSP-d4) in D2O was used as a quantitative reference. The levels of l-citrulline and sugars were measured in less than 6min. This rapid quantitation method was validated for specificity, linearity, accuracy, precision, reproducibility, and robustness. The limit of detection for l-citrulline was 38µg/mL and the limit of quantification was 71µg/mL; for sugars, the limits were 59-94µg/mL and 120µg/mL, respectively. This method can be used widely for confirmation and rapid quantitation of multiple compounds in large number of biological or breeding samples for routine analysis. PMID:27130118

  19. Refinement of the ECETOC approach to identify endocrine disrupting properties of chemicals in ecotoxicology.

    Science.gov (United States)

    Weltje, Lennart; Wheeler, James R; Weyers, Arnd; Galay-Burgos, Malyka

    2013-12-16

    To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed. Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments. Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment. These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical. Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified. Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is 'negligible exposure'. This paper discusses and provides proposals on how to apply these concepts for assessment of substances.

  20. A stepwise approach to identify intellectual disabilities in the criminal justice system

    Directory of Open Access Journals (Sweden)

    Valentina Cabral Iversen

    2010-07-01

    Full Text Available A significant proportion of the prison inmates have an IQ level corresponding to intellectual disability (ID or borderline ID. These persons are rarely identified and subsequently not offered any compensation for their learning and comprehension deficits. The purpose of this study was to explore and help providing methods for better identification of ID at an early stage during criminal proceedings. 143 randomly selected prisoners serving sentences in prisons were assessed using The Wechsler Abbreviated Scale of Intelligence (WASI and the Hayes Ability Screening Index (HASI while a semi-structured interview was carried out to obtain data on health as well as social and criminological issues. A total of 10.8% (n = 15 of the participants showed an IQ below 70. From previous analyses of the semistructured interview, a checklist was extracted and found to have good predictive validity on ID (AUC= 93%. The resulting identification referred 32% (n= 46 of the sample for comprehensive assessment. Within this group, all participants with an IQ below70 were included. Identification through this checklist, the screening and a full assessment is essential in improving the quality of the services.

  1. Know Your Monkey: Identifying Primate Conservation Challenges in an Indigenous Kichwa Community Using an Ethnoprimatological Approach.

    Science.gov (United States)

    Stafford, Ciara A; Alarcon-Valenzuela, Javiera; Patiño, Javier; Preziosi, Richard F; Sellers, William I

    2016-01-01

    Increasing pressure on tropical forests is continually highlighting the need to find new solutions that mitigate the impact of human populations on biodiversity. However, developing solutions that can tackle the drivers of anthropogenic pressure, or at least take them into account, hinges upon building a good understanding of the culture and perceptions of local people. This study aims to provide an overview of the ethnoprimatology of an indigenous Kichwa community in the Ecuadorian Amazon that maintains a traditional lifestyle but also has good access to markets. We examine whether primates are seen as a distinctive group and their relative importance as sources of bushmeat and as household pets. Pile-sorting exercises revealed that although locals generally group members of the order Primates together, tree-dwelling non-primates including sloths, coatis, kinkajous and tamanduas are also frequently classified as 'monkeys'. The perceived importance of primates to the forest and the community lay more in their potential as bushmeat, and only 1 respondent identified an ecological role for the group in terms of seed dispersal. Gaining a better understanding of local perceptions will allow for better-informed conservation decisions that are more aware of potential impacts and are more likely to gain community support. PMID:27093638

  2. Know Your Monkey: Identifying Primate Conservation Challenges in an Indigenous Kichwa Community Using an Ethnoprimatological Approach.

    Science.gov (United States)

    Stafford, Ciara A; Alarcon-Valenzuela, Javiera; Patiño, Javier; Preziosi, Richard F; Sellers, William I

    2016-01-01

    Increasing pressure on tropical forests is continually highlighting the need to find new solutions that mitigate the impact of human populations on biodiversity. However, developing solutions that can tackle the drivers of anthropogenic pressure, or at least take them into account, hinges upon building a good understanding of the culture and perceptions of local people. This study aims to provide an overview of the ethnoprimatology of an indigenous Kichwa community in the Ecuadorian Amazon that maintains a traditional lifestyle but also has good access to markets. We examine whether primates are seen as a distinctive group and their relative importance as sources of bushmeat and as household pets. Pile-sorting exercises revealed that although locals generally group members of the order Primates together, tree-dwelling non-primates including sloths, coatis, kinkajous and tamanduas are also frequently classified as 'monkeys'. The perceived importance of primates to the forest and the community lay more in their potential as bushmeat, and only 1 respondent identified an ecological role for the group in terms of seed dispersal. Gaining a better understanding of local perceptions will allow for better-informed conservation decisions that are more aware of potential impacts and are more likely to gain community support.

  3. A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Peng Jiang

    2015-05-01

    Full Text Available Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders.

  4. Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

    Science.gov (United States)

    Polachini, Giovana M.; Sobral, Lays M.; Mercante, Ana M. C.; Paes-Leme, Adriana F.; Xavier, Flávia C. A.; Henrique, Tiago; Guimarães, Douglas M.; Vidotto, Alessandra; Fukuyama, Erica E.; Góis-Filho, José F.; Cury, Patricia M.; Curioni, Otávio A.; Michaluart Jr, Pedro; Silva, Adriana M. A.; Wünsch-Filho, Victor; Nunes, Fabio D.; Leopoldino, Andréia M.; Tajara, Eloiza H.

    2012-01-01

    The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the “more-aggressive” group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the “less-aggressive” group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas. PMID:23227181

  5. Geostatistical approach for identifying scale-specific correlations between soil thickness and topographic attributes

    Science.gov (United States)

    Bourennane, Hocine; Salvador-Blanes, Sébastien; Couturier, Alain; Chartin, Caroline; Pasquier, Catherine; Hinschberger, Florent; Macaire, Jean-Jacques; Daroussin, Joël

    2014-09-01

    better for predicting soil thickness than the model based on large-scale structure (Model-L). The effects of topographic attribute data sources as explanatory variables for modeling ST are less significant than the effects of the two models for mapping. Moreover, extrapolation of the model-S beyond the area where it was generated is appropriate. The decomposition process is associated with a modeling approach, such as the PLSR, which accounts for the collinearity between predictor variables and leads to an efficient prediction model. These results are important for modeling soil properties based on topographic attributes and for spatially generalizing models that have been established over small to large areas. Thus, in the presence of nested variogram models, the correlations between variables of interest and auxiliary information should be improved by filtering out some of the spatial structures by factorial kriging. The information filtered is associated with an appropriate approach for modeling when collinearity occurs between the predictor variables and provides a suitable model for predicting and spatially generalizing a locally established model.

  6. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins.

    Directory of Open Access Journals (Sweden)

    Siddarth Soni

    Full Text Available Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID. The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue.General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2, Nexilin (NEXN, Popeye-domain-containg-protein 2 (POPDC2 and thioredoxin-related-transmembrane-protein 2 (TMX2 and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes.The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart.

  7. Considerations on a data-driven approach to identify plant's imprint on ecosystem functioning

    Science.gov (United States)

    Musavi, Talie; Kattge, Jens; Mahecha, Miguel; Reichstein, Markus; Van de Weg, Martine Janet; Van Bodegom, Peter; Bahn, Michael; Migliavacca, Mirco; Wirth, Christian; Reich, Peter

    2015-04-01

    Terrestrial ecosystems strongly determine the exchange of carbon, water and energy between the biosphere and atmosphere. These exchanges are influenced and partly driven by environmental conditions (e.g. local meteorology, soils), but generally mediated by organisms. In commonly used terrestrial biosphere models, this principle is implemented by process-based descriptions of plant functioning at the organ level. In order to validate these model formulations, we need an independent empirical approach to understand the plant's imprint on ecosystem functioning. We use land-atmosphere exchange of fluxes of CO2, H2O and energy in tandem with environmental controls available in FLUXNET to quantify "ecosystem functional properties" (EFPs). The latter are generally time-invariant ecosystem specific properties, for instance process sensitivities or efficiencies that shape ecosystem scale responses. Our crucial question is if plant traits measured at the organ level (available e.g. in the TRY database) can elucidate the characteristics of EFPs. In this study we follow this new avenue and link the two global databases FLUXNET and TRY to study the role of plants for biogeochemical cycles across a large number of different globally distributed ecosystem types. We aim to address emerging difficulties and possible solutions. For instance, we show that using average values of plant traits from TRY that are not necessarily measured at the fluxnet sites is of use but has clear limitations. However having information on the amount of vegetation at the sites derived from remote sensing is needed for weighting the plant traits. In addition, we have to consider that EFPs are not really time-invariant and subject to alterations after disturbance, meteorological extremes, management etc. Overall, we provide an outlook on perspectives and applications of empirical analyses of plants' imprint on ecosystem functioning by combining remote sensing, in situ measured plant traits and ecosystem

  8. Coordinating Group report

    International Nuclear Information System (INIS)

    In December 1992, western governors and four federal agencies established a Federal Advisory Committee to Develop On-site Innovative Technologies for Environmental Restoration and Waste Management (the DOIT Committee). The purpose of the Committee is to advise the federal government on ways to improve waste cleanup technology development and the cleanup of federal sites in the West. The Committee directed in January 1993 that information be collected from a wide range of potential stakeholders and that innovative technology candidate projects be identified, organized, set in motion, and evaluated to test new partnerships, regulatory approaches, and technologies which will lead to improve site cleanup. Five working groups were organized, one to develop broad project selection and evaluation criteria and four to focus on specific contaminant problems. A Coordinating Group comprised of working group spokesmen and federal and state representatives, was set up to plan and organize the routine functioning of these working groups. The working groups were charged with defining particular contaminant problems; identifying shortcomings in technology development, stakeholder involvement, regulatory review, and commercialization which impede the resolution of these problems; and identifying candidate sites or technologies which could serve as regional innovative demonstration projects to test new approaches to overcome the shortcomings. This report from the Coordinating Group to the DOIT Committee highlights the key findings and opportunities uncovered by these fact-finding working groups. It provides a basis from which recommendations from the DOIT Committee to the federal government can be made. It also includes observations from two public roundtables, one on commercialization and another on regulatory and institutional barriers impeding technology development and cleanup

  9. A Bayesian Approach to Identifying New Risk Factors for Dementia: A Nationwide Population-Based Study.

    Science.gov (United States)

    Wen, Yen-Hsia; Wu, Shihn-Sheng; Lin, Chun-Hung Richard; Tsai, Jui-Hsiu; Yang, Pinchen; Chang, Yang-Pei; Tseng, Kuan-Hua

    2016-05-01

    Dementia is one of the most disabling and burdensome health conditions worldwide. In this study, we identified new potential risk factors for dementia from nationwide longitudinal population-based data by using Bayesian statistics.We first tested the consistency of the results obtained using Bayesian statistics with those obtained using classical frequentist probability for 4 recognized risk factors for dementia, namely severe head injury, depression, diabetes mellitus, and vascular diseases. Then, we used Bayesian statistics to verify 2 new potential risk factors for dementia, namely hearing loss and senile cataract, determined from the Taiwan's National Health Insurance Research Database.We included a total of 6546 (6.0%) patients diagnosed with dementia. We observed older age, female sex, and lower income as independent risk factors for dementia. Moreover, we verified the 4 recognized risk factors for dementia in the older Taiwanese population; their odds ratios (ORs) ranged from 3.469 to 1.207. Furthermore, we observed that hearing loss (OR = 1.577) and senile cataract (OR = 1.549) were associated with an increased risk of dementia.We found that the results obtained using Bayesian statistics for assessing risk factors for dementia, such as head injury, depression, DM, and vascular diseases, were consistent with those obtained using classical frequentist probability. Moreover, hearing loss and senile cataract were found to be potential risk factors for dementia in the older Taiwanese population. Bayesian statistics could help clinicians explore other potential risk factors for dementia and for developing appropriate treatment strategies for these patients.

  10. Biosensor-Based Approach Identifies Four Distinct Calmodulin-Binding Domains in the G Protein-Coupled Estrogen Receptor 1

    OpenAIRE

    Tran, Quang-Kim; VerMeer, Mark

    2014-01-01

    The G protein-coupled estrogen receptor 1 (GPER) has been demonstrated to participate in many cellular functions, but its regulatory inputs are not clearly understood. Here we describe a new approach that identifies GPER as a calmodulin-binding protein, locates interaction sites, and characterizes their binding properties. GPER coimmunoprecipitates with calmodulin in primary vascular smooth muscle cells under resting conditions, which is enhanced upon acute treatment with either specific liga...

  11. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  12. A simple approach to identify critical source areas for phosphorus leaching in the Netherlands

    Science.gov (United States)

    van der Salm, C.; Schoumans, O. F.; Walvoort, D.; Groenendijk, P.; Pleijter, M.

    2009-04-01

    High soil phopshorus contents in agricultural soils in the Netherlands cause excessive losses of P to surface waters. The reductions in P application rates in the present manure policy are not sufficient to reach surface water quality standards resulting from the European Water Framework Directive in all catchments by 2015. Accordingly, additional measures have to be considered to further reduce P loading to surface water. For a cost effective implementation of these measures an instrument to identify critical source areas for phosphorus leaching is indispensable. In the Netherlands phosphorus leaching at a national scale is simulated with a comprehensive mechanistic simulation model (STONE, Wolf et al., 2005) focusing on changes in P leaching with time. The identification of critical source areas requires simulations at a high spatial resolution. STONE is less suitable for this purpose, because of the large number of input parameters required by this complex model. For this reason, a simple model (PLEASE: Phosphorus LEAching from Soils to the Environment; Schoumans et al., in prep.) has been developed based on the same mechanistic process description for inorganic P as the complex model STONE and a simplified description of the lateral flow of water from soil to surface waters. With this model P leaching to surface waters can be calculated using readily available information of field characteristics like depth of the groundwater table, precipitation surplus and P status and phosphorus adsorption capacity of the soil. To evaluate the performance of the model, it was applied to the Netherlands using the same input as the national model. Parameterised in this way, PLEASE is a metamodel of STONE. The model was also tested on two small catchments: a catchment with sandy soils and high P accumulation and a clay catchment with a moderate P accumulation. The application at the national scale showed that the overall order of magnitude of the calculated leaching fluxes was

  13. Towards a Carbon-Neutral Energy Sector: Opportunities and Challenges of Coordinated Bioenergy Supply Chains-A PSE Approach

    Directory of Open Access Journals (Sweden)

    Luis Puigjaner

    2015-06-01

    Full Text Available The electricity generation sector needs to reduce its environmental impact and dependence on fossil fuel, mainly from coal. Biomass is one of the most promising future options to produce electricity, given its potential contribution to climate change mitigation. Even though biomass is an old source of energy, it is not yet a well-established commodity. The use of biomass in large centralised systems requires the establishment of delivery channels to provide the desired feedstock with the necessary attributes, at the right time and place. In terms of time to deployment and cost of the solution, co-combustion/co-gasification of biomass and coal are presented as transition and short-medium term alternatives towards a carbon-neutral energy sector. Hence, there is a need to assess an effective introduction of co-combustion/co-gasification projects in the current electricity production share. The purpose of this work is to review recent steps in Process Systems Engineering towards bringing into reality individualised and ad-hoc solutions, by building a common but adjustable design platform to tailored approaches of biomass-based supply chains. Current solutions and the latest developments are presented and future needs under study are also identified.

  14. Potential of calcium isotopes to identify fractionations in vegetation: experimental approach

    Science.gov (United States)

    Cobert, F.; Schmitt, A.; Bourgade, P.; Stille, P.; Chabaux, F. J.; Badot, P.; Jaegler, T.

    2010-12-01

    This study aims to better understand the role of vegetation on the Ca cycle at the level of the critical zone of the Earth, in order to specify the mechanisms controlling the Ca absorption by plants at the rock/plant interface. To do this, we performed experiments using hydroponic plant cultures in a way that we could control the cooccuring geochemical and biological processes and determine the impact of the nutritive solution on the Ca cycle within plants. A dicotyledon and calcicole plant with rapid growth, the French bean (Phaseolus vulgaris L.), has been chosen to have access to one complete growth cycle. Several experiments have been conducted with two Ca concentrations, 5 (L) and 60 (H) ppm and two pH values (4 and 6) in the nutritive solution, for which the Ca concentration was maintained constant, so its Ca content is considered to be infinite. We determined Ca concentrations and isotopic ratios in the nutritive solution and in different organs (main roots, secondary roots, old and young stems, old and young leaves and fruits) at two different growth stages (10 days and 6 weeks). Our results show, in accord with previously published field studies, that the bean organs are all enriched in the light 40Ca isotope compared to the nutritive solution (e.g. Wigand et al., 2005; Page et al., 2008; Cenki-Tok et al., 2009; Holmden and Bélanger, 2010). We identify two fractionation levels. The first occurs during the uptake of the nutrient elements by the lateral roots. This implies that the main mechanisms of light isotope enrichments in the plant are due to electrochemical gradient transport processes taking place at this interface. The second fractionation can be observed within the plant itself and is due to the nature of the considered organ itself. Indeed structural reservoirs (primary roots, stem, reproductive organs) incorporate more the light 40Ca isotope compared to the transfer reservoirs (lateral roots, xylem sap, leaves). This could be linked to ion

  15. 2. Research Coordination Meeting of the Coordinated Research Project on Integrated Analytical Approaches to Assess Indicators of the Effectiveness of Pesticide Management Practices at the Catchment Scale (D5.20.35); Vienna, Austria; 9-13 February 2009

    International Nuclear Information System (INIS)

    The Second Research Coordination Meeting (RCM) of Coordinated Research Project (CRP) on Integrated Analytical Approaches to Assess Indicators of the Effectiveness of Pesticide Management Practices at the Catchment Scale was held at IAEA Headquarters in Vienna, Austria, from 9-13 February 2009. The meeting was attended by research contract/agreement holders from Argentina, Australia, Brazil, Bulgaria, Chile, China, Costa Rica, Cyprus, Ecuador, Germany, Kenya, India and the Philippines, as well as observers from Costa Rica and Slovakia. The objectives of the meeting were to share and disseminate the results of the first two years of the programme, to agree on a work plan for the next two years of the project and to strengthen the role of participating laboratories in the assessment of the implementation of good agricultural practices (GAP). Specifically, to: - consolidate the network of laboratories to assess indicators of pesticide management practices in water and soil/sediment samples; - disseminate information about the results obtained from the first two years of work; - revise individual work plans for the next two years of the project; - fine tune the risk assessment results using the pesticide impact rating index (PIRI); - update skills in the analysis of pesticide residues in water/soil/sediments; - disseminate information about bioassays relevant to the CRP, and; - familiarize participants with the use of flow meters, GPS and GIS and new LIMS developments

  16. Bidirectional coupling between astrocytes and neurons mediates learning and dynamic coordination in the brain: a multiple modeling approach.

    Directory of Open Access Journals (Sweden)

    John J Wade

    Full Text Available In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a "learning signal" to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity, and the modeling strategy may be extended to coordination among remote neuron clusters.

  17. A weight-of-evidence approach to identify nanomaterials in consumer products: a case study of nanoparticles in commercial sunscreens.

    Science.gov (United States)

    Cuddy, Michael F; Poda, Aimee R; Moser, Robert D; Weiss, Charles A; Cairns, Carolyn; Steevens, Jeffery A

    2016-01-01

    Nanoscale ingredients in commercial products represent a point of emerging environmental concern due to recent findings that correlate toxicity with small particle size. A weight-of-evidence (WOE) approach based upon multiple lines of evidence (LOE) is developed here to assess nanomaterials as they exist in consumer product formulations, providing a qualitative assessment regarding the presence of nanomaterials, along with a baseline estimate of nanoparticle concentration if nanomaterials do exist. Electron microscopy, analytical separations, and X-ray detection methods were used to identify and characterize nanomaterials in sunscreen formulations. The WOE/LOE approach as applied to four commercial sunscreen products indicated that all four contained at least 10% dispersed primary particles having at least one dimension <100 nm in size. Analytical analyses confirmed that these constituents were comprised of zinc oxide (ZnO) or titanium dioxide (TiO2). The screening approaches developed herein offer a streamlined, facile means to identify potentially hazardous nanomaterial constituents with minimal abrasive processing of the raw material.

  18. Approaches to identifying reservoir heterogeneity and reserve growth opportunities from subsurface data: The Oficina Formation, Budare field, Venezuela

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, D.S.; Raeuchle, S.K.; Holtz, M.H. [Bureau of Economic Geology, Austin, TX (United States)] [and others

    1997-08-01

    We applied an integrated geologic, geophysical, and engineering approach devised to identify heterogeneities in the subsurface that might lead to reserve growth opportunities in our analysis of the Oficina Formation at Budare field, Venezuela. The approach involves 4 key steps: (1) Determine geologic reservoir architecture; (2) Investigate trends in reservoir fluid flow; (3) Integrate fluid flow trends with reservoir architecture; and (4) Estimate original oil-in-place, residual oil saturation, and remaining mobile oil, to identify opportunities for reserve growth. There are three main oil-producing reservoirs in the Oficina Formation that were deposited in a bed-load fluvial system, an incised valley-fill, and a barrier-strandplain system. Reservoir continuity is complex because, in addition to lateral facies variability, the major Oficina depositional systems were internally subdivided by high-frequency stratigraphic surfaces. These surfaces define times of intermittent lacustrine and marine flooding events that punctuated the fluvial and marginal marine sedimentation, respectively. Syn and post depositional faulting further disrupted reservoir continuity. Trends in fluid flow established from initial fluid levels, response to recompletion workovers, and pressure depletion data demonstrated barriers to lateral and vertical fluid flow caused by a combination of reservoir facies pinchout, flooding shale markers, and the faults. Considerable reserve growth potential exists at Budare field because the reservoir units are highly compartment by the depositional heterogeneity and structural complexity. Numerous reserve growth opportunities were identified in attics updip of existing production, in untapped or incompletely drained compartments, and in field extensions.

  19. Water coordination structures and the excess free energy of the liquid

    CERN Document Server

    Merchant, Safir; Asthagiri, D

    2011-01-01

    For a distinguished water molecule, the solute water, we assess the contribution of each coordination state to its excess chemical potential, using a molecular aufbau approach. In this approach, we define a coordination sphere, the inner-shell, and separate the excess chemical potential into packing, outer-shell, and local chemical contributions; the coordination state is defined by the number of solvent water molecules within the coordination sphere. The packing term accounts for the free energy of creating a solute-free coordination sphere in the liquid. The outer-shell term accounts for the interaction of the solute with the fluid outside the coordination sphere and it is accurately described by a Gaussian model of hydration for coordination radii greater than the minimum of the oxygen-oxygen pair correlation function. Consistent with the conventional radial cut-off used for defining hydrogen-bonds in liquid water, theory helps identify a chemically meaningful coordination radius. The local chemical contri...

  20. Geometry of trigonal boron coordination sphere in boronic acids derivatives - a bond-valence vector model approach.

    Science.gov (United States)

    Czerwińska, Karolina; Madura, Izabela D; Zachara, Janusz

    2016-04-01

    The systematic analysis of the geometry of three-coordinate boron in boronic acid derivatives with a common [CBO2] skeleton is presented. The study is based on the bond-valence vector (BVV) model [Zachara (2007). Inorg. Chem. 46, 9760-9767], a simple tool for the identification and quantitative estimation of both steric and electronic factors causing deformations of the coordination sphere. The empirical bond-valence (BV) parameters in the exponential equation [Brown & Altermatt (1985). Acta Cryst. B41, 244-247] rij and b, for B-O and B-C bonds were determined using data deposited in the Cambridge Structural Database. The values obtained amount to rBO = 1.364 Å, bBO = 0.37 Å, rBC = 1.569 Å, bBC = 0.28 Å, and they were further used in the calculation of BVV lengths. The values of the resultant BVV were less than 0.10 v.u. for 95% of the set comprising 897 [CBO2] fragments. Analysis of the distribution of BVV components allowed for the description of subtle in- and out-of plane deviations from the `ideal' (sp(2)) geometry of boron coordination sphere. The distortions specific for distinct groups of compounds such as boronic acids, cyclic and acyclic esters, benzoxaboroles and hemiesters were revealed. In cyclic esters the direction of strains was found to be controlled by the ring size effect. It was shown that the syn or anti location of substituents on O atoms is decisive for the deformations direction for both acids and acyclic esters. The greatest strains were observed in the case of benzoxaboroles which showed the highest deviation from the zero value of the resultant BVV. The out-of-plane distortions, described by the vz component of the resultant BVV, were ascertained to be useful in the identification of weak secondary interactions on the fourth coordination site of the boron centre. PMID:27048726

  1. Identifying and Quantifying Cultural Factors That Matter to the IT Workforce: An Approach Based on Automated Content Analysis

    DEFF Research Database (Denmark)

    Schmiedel, Theresa; Müller, Oliver; Debortoli, Stefan;

    2016-01-01

    Organizational culture represents a key success factor in highly competitive environments, such as, the IT sector. Thus, IT companies need to understand what makes up a culture that fosters employee performance. While existing research typically uses self-report questionnaires to study the relation...... of culture and the success of companies, the validity of this approach is often discussed and researchers call for new ways of studying culture. Therefore, our research goal is to present an alternative approach to culture analysis for examining which cultural factors matter to the IT workforce. Our study...... builds on 112,610 online reviews of Fortune 500 IT companies collected from Glassdoor, an online platform on which current and former employees can anonymously review companies and their management. We perform an automated content analysis to identify cultural factors that employees emphasize...

  2. 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

  3. The promoter competition assay (PCA): a new approach to identify motifs involved in the transcriptional activity of reporter genes.

    Science.gov (United States)

    Hube, Florent; Myal, Yvonne; Leygue, Etienne

    2006-05-01

    Identifying particular motifs responsible for promoter activity is a crucial step toward the development of new gene-based preventive and therapeutic strategies. However, to date, experimental methods to study promoter activity remain limited. We present in this report a promoter competition assay designed to identify, within a given promoter region, motifs critical for its activity. This assay consists in co-transfecting the promoter to be analyzed and double-stranded oligonucleotides which will compete for the binding of transcription factors. Using the recently characterized SBEM promoter as model, we first delineated the feasibility of the method and optimized the experimental conditions. We then identified, within an 87-bp region responsible for a strong expression of the reporter gene, an octamer-binding site essential for its transcriptional regulation. The importance of this motif has been confirmed by site-directed mutagenesis. The promoter competition assay appears to be a fast and efficient approach to identify, within a given promoter sequence, sites critical for its activity.

  4. A combined approach to data mining of textual and structured data to identify cancer-related targets

    Directory of Open Access Journals (Sweden)

    Adelstein S James

    2006-07-01

    Full Text Available Abstract Background We present an effective, rapid, systematic data mining approach for identifying genes or proteins related to a particular interest. A selected combination of programs exploring PubMed abstracts, universal gene/protein databases (UniProt, InterPro, NCBI Entrez, and state-of-the-art pathway knowledge bases (LSGraph and Ingenuity Pathway Analysis was assembled to distinguish enzymes with hydrolytic activities that are expressed in the extracellular space of cancer cells. Proteins were identified with respect to six types of cancer occurring in the prostate, breast, lung, colon, ovary, and pancreas. Results The data mining method identified previously undetected targets. Our combined strategy applied to each cancer type identified a minimum of 375 proteins expressed within the extracellular space and/or attached to the plasma membrane. The method led to the recognition of human cancer-related hydrolases (on average, ~35 per cancer type, among which were prostatic acid phosphatase, prostate-specific antigen, and sulfatase 1. Conclusion The combined data mining of several databases overcame many of the limitations of querying a single database and enabled the facile identification of gene products. In the case of cancer-related targets, it produced a list of putative extracellular, hydrolytic enzymes that merit additional study as candidates for cancer radioimaging and radiotherapy. The proposed data mining strategy is of a general nature and can be applied to other biological databases for understanding biological functions and diseases.

  5. Facilitating a stakeholder-led approach to the development of Mediterranean climate services: co-ordinating the CLIM-RUN case studies

    Science.gov (United States)

    Goodess, C. M.

    2012-04-01

    The CLIM-RUN case studies provide a real-world context for bringing together experts on the demand and supply side of climate services. They are essential to the CLIM-RUN objective of using iterative and bottom-up (i.e., stakeholder led) approaches for optimizing the two-way information transfer between climate experts and stakeholders. The region of interest for CLIM-RUN is the Mediterranean, which is a recognised climate change hotspot (i.e., a region particularly sensitive and vulnerable to global warming) and which does not currently have developed climate service networks such as exist in a number of Central and Northern European countries. The case studies focus on the energy and tourism sectors, but also include a cross-cutting study on wild fires (an issue of increasing concern in the Mediterranean) as well as a cross-sectorial integrated case study for the Venice lagoon. They span coastal (e.g., Tunisia and Croatia), island (e.g., Cyprus) and mountain (e.g., Savoie) environments, the eastern (e.g., Greece) to western (e.g., Spain, Morocco) Mediterranean regions, and regional to local foci. Stakeholder involvement has been critical from the start of the project in March 2011, with a series of targeted workshops helping to define the framework for each case study. Two specific workshop objectives were to (i) better understand who are the climate services stakeholders and (ii) what they need/want from climate services (both in terms of data products and broader knowledge). Many of the workshops were held in local languages to maximise stakeholder participation, with expert knowledge provided by the CLIM-RUN climate and stakeholder expert teams (the CET and SET). Following the workshops, CET members are 'translating' the user needs into specific requirements from climate observations and models and identifying areas where additional modelling and analysis are required. As part of the central co-ordination of the case studies, a perception and data needs

  6. Do maize models capture the impacts of heat and drought stresses on yield? Using algorithm ensembles to identify successful approaches.

    Science.gov (United States)

    Jin, Zhenong; Zhuang, Qianlai; Tan, Zeli; Dukes, Jeffrey S; Zheng, Bangyou; Melillo, Jerry M

    2016-09-01

    Stresses from heat and drought are expected to increasingly suppress crop yields, but the degree to which current models can represent these effects is uncertain. Here we evaluate the algorithms that determine impacts of heat and drought stress on maize in 16 major maize models by incorporating these algorithms into a standard model, the Agricultural Production Systems sIMulator (APSIM), and running an ensemble of simulations. Although both daily mean temperature and daylight temperature are common choice of forcing heat stress algorithms, current parameterizations in most models favor the use of daylight temperature even though the algorithm was designed for daily mean temperature. Different drought algorithms (i.e., a function of soil water content, of soil water supply to demand ratio, and of actual to potential transpiration ratio) simulated considerably different patterns of water shortage over the growing season, but nonetheless predicted similar decreases in annual yield. Using the selected combination of algorithms, our simulations show that maize yield reduction was more sensitive to drought stress than to heat stress for the US Midwest since the 1980s, and this pattern will continue under future scenarios; the influence of excessive heat will become increasingly prominent by the late 21st century. Our review of algorithms in 16 crop models suggests that the impacts of heat and drought stress on plant yield can be best described by crop models that: (i) incorporate event-based descriptions of heat and drought stress, (ii) consider the effects of nighttime warming, and (iii) coordinate the interactions among multiple stresses. Our study identifies the proficiency with which different model formulations capture the impacts of heat and drought stress on maize biomass and yield production. The framework presented here can be applied to other modeled processes and used to improve yield predictions of other crops with a wide variety of crop models. PMID:27251794

  7. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  8. An unbiased approach to identify genes involved in development in a turtle with temperature-dependent sex determination

    Directory of Open Access Journals (Sweden)

    Chojnowski Jena L

    2012-07-01

    Full Text Available Abstract Background Many reptiles exhibit temperature-dependent sex determination (TSD. The initial cue in TSD is incubation temperature, unlike genotypic sex determination (GSD where it is determined by the presence of specific alleles (or genetic loci. We used patterns of gene expression to identify candidates for genes with a role in TSD and other developmental processes without making a priori assumptions about the identity of these genes (ortholog-based approach. We identified genes with sexually dimorphic mRNA accumulation during the temperature sensitive period of development in the Red-eared slider turtle (Trachemys scripta, a turtle with TSD. Genes with differential mRNA accumulation in response to estrogen (estradiol-17β; E2 exposure and developmental stages were also identified. Results Sequencing 767 clones from three suppression-subtractive hybridization libraries yielded a total of 581 unique sequences. Screening a macroarray with a subset of those sequences revealed a total of 26 genes that exhibited differential mRNA accumulation: 16 female biased and 10 male biased. Additional analyses revealed that C16ORF62 (an unknown gene and MALAT1 (a long noncoding RNA exhibited increased mRNA accumulation at the male producing temperature relative to the female producing temperature during embryonic sexual development. Finally, we identified four genes (C16ORF62, CCT3, MMP2, and NFIB that exhibited a stage effect and five genes (C16ORF62, CCT3, MMP2, NFIB and NOTCH2 showed a response to E2 exposure. Conclusions Here we report a survey of genes identified using patterns of mRNA accumulation during embryonic development in a turtle with TSD. Many previous studies have focused on examining the turtle orthologs of genes involved in mammalian development. Although valuable, the limitations of this approach are exemplified by our identification of two genes (MALAT1 and C16ORF62 that are sexually dimorphic during embryonic development. MALAT1 is

  9. Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers

    Science.gov (United States)

    DeVries, Paul; Aldrich, Robert

    2015-08-01

    A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m3/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.

  10. Identifying robust communities and multi-community nodes by combining top-down and bottom-up approaches to clustering.

    Science.gov (United States)

    Gaiteri, Chris; Chen, Mingming; Szymanski, Boleslaw; Kuzmin, Konstantin; Xie, Jierui; Lee, Changkyu; Blanche, Timothy; Chaibub Neto, Elias; Huang, Su-Chun; Grabowski, Thomas; Madhyastha, Tara; Komashko, Vitalina

    2015-11-09

    Biological functions are carried out by groups of interacting molecules, cells or tissues, known as communities. Membership in these communities may overlap when biological components are involved in multiple functions. However, traditional clustering methods detect non-overlapping communities. These detected communities may also be unstable and difficult to replicate, because traditional methods are sensitive to noise and parameter settings. These aspects of traditional clustering methods limit our ability to detect biological communities, and therefore our ability to understand biological functions. To address these limitations and detect robust overlapping biological communities, we propose an unorthodox clustering method called SpeakEasy which identifies communities using top-down and bottom-up approaches simultaneously. Specifically, nodes join communities based on their local connections, as well as global information about the network structure. This method can quantify the stability of each community, automatically identify the number of communities, and quickly cluster networks with hundreds of thousands of nodes. SpeakEasy shows top performance on synthetic clustering benchmarks and accurately identifies meaningful biological communities in a range of datasets, including: gene microarrays, protein interactions, sorted cell populations, electrophysiology and fMRI brain imaging.

  11. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-01-01

    Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication

  12. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell

  13. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  14. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  15. A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

    Science.gov (United States)

    Popp, Oliver; Müller, Dirk; Didzus, Katharina; Paul, Wolfgang; Lipsmeier, Florian; Kirchner, Florian; Niklas, Jens; Mauch, Klaus; Beaucamp, Nicola

    2016-09-01

    In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance. The approach combines metabolite profiling with multivariate data analysis and fluxomics to enable a data-driven mechanistic analysis of key metabolic traits associated with desired cell phenotypes. We applied the methodology to quantify and compare metabolic performance in a set of 10 recombinant CHO-K1 producer clones and a host cell line. The comprehensive characterization enabled us to derive an extended set of clone performance criteria that not only captured growth and product formation, but also incorporated information on intracellular clone physiology and on metabolic changes during the process. These criteria served to establish a quantitative clone ranking and allowed us to identify metabolic differences between high-producing CHO-K1 clones yielding comparably high product titers. Through multivariate data analysis of the combined metabolite and flux data we uncovered common metabolic traits characteristic of high-producer clones in the screening setup. This included high intracellular rates of glutamine synthesis, low cysteine uptake, reduced excretion of aspartate and glutamate, and low intracellular degradation rates of branched-chain amino acids and of histidine. Finally, the above approach was integrated into a workflow that enables standardized high-content selection of CHO producer clones in a high-throughput fashion. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic

  16. Patient- and Family-Identified Problems of Traumatic Brain Injury: Value and Utility of a Target Outcome Approach to Identifying the Worst Problems

    Directory of Open Access Journals (Sweden)

    Laraine Winter

    2016-01-01

    Full Text Available Purpose: This study aimed to identify the sequelae of traumatic brain injury (TBI that are most troubling to veterans with TBI and their families and identify veteran-family differences in content and ranking. Instead of standardized measures of symptom frequency or severity, which may be insensitive to change or intervention effects, we used a target outcome measure for veterans with TBI and their key family members, which elicited open-ended reports concerning the three most serious TBI-related problems. This was followed by Likert-scaled ratings of difficulty in managing the problem. Methods: In this cross-sectional study, interviews were conducted in veterans’ homes. Participants included 83 veterans with TBI diagnosed at a Veterans Affairs medical rehabilitation service and a key family member of each veteran. We utilized open-ended questions to determine the problems caused by TBI within the last month. Sociodemographic characteristics of veterans and family members, and veterans’ military and medical characteristics were collected. A coding scheme was developed to categorize open-ended responses. Results: Families identified nearly twice as many categories of problems as did veterans, and veterans and families ranked problem categories very differently. Veterans ranked cognitive and physical problems worst; families ranked emotional and interpersonal problems worst. Conclusions: Easily administered open-ended questions about the most troubling TBI-related problems yield novel insights and reveal important veteran-family discrepancies.

  17. IDENTIFYING NETWORK LOAD BALANCING REQUIREMENTS ON HISTORICAL TRAFFIC FLOW USING MACHINE LEARNING APPROACH FOR FLEXIBLE MULTIPATH NETWORKS

    Directory of Open Access Journals (Sweden)

    K BALAMURUGAN

    2010-08-01

    Full Text Available Multipath routing uses several paths to distribute traffic from a source to destination. This not only improves network performance but also achieves load balancing and fault tolerance. Though multipath routing is not deployed widely in the internet, current systems chooses the paths with the same lowest cost to the destination and the same administrative distance.In this paper we propose a flexible multipath network wherein multipath routing algorithm is invoked when the quality of service is affected. Our proposal provides a method to gradually shift from a single path existing network to a reliable multipath network in the future.We have used machine learning approach to identify the instance when network load balancing is required with good results.

  18. A Dynamic Combinatorial Approach for Identifying Side Groups that Stabilize DNA-Templated Supramolecular Self-Assemblies

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    Delphine Paolantoni

    2015-02-01

    Full Text Available DNA-templated self-assembly is an emerging strategy for generating functional supramolecular systems, which requires the identification of potent multi-point binding ligands. In this line, we recently showed that bis-functionalized guanidinium compounds can interact with ssDNA and generate a supramolecular complex through the recognition of the phosphodiester backbone of DNA. In order to probe the importance of secondary interactions and to identify side groups that stabilize these DNA-templated self-assemblies, we report herein the implementation of a dynamic combinatorial approach. We used an in situ fragment assembly process based on reductive amination and tested various side groups, including amino acids. The results reveal that aromatic and cationic side groups participate in secondary supramolecular interactions that stabilize the complexes formed with ssDNA.

  19. Identifying emotional and behavioral risk among gifted and nongifted children: A multi-gate, multi-informant approach.

    Science.gov (United States)

    Eklund, Katie; Tanner, Nick; Stoll, Katie; Anway, Leslie

    2015-06-01

    The purpose of the current investigation was to compare 1,206 gifted and nongifted elementary students on the identification of emotional and behavioral risk (EBR) as rated by teachers and parents using a multigate, multi-informant approach to assessment. The Parent and Teacher Behavioral Assessment System for Children, Second Edition (BASC-2) and the Behavioral and Emotional Screening System were used to assess behavioral functioning as rated by teachers and parents. There were significant differences between the number of gifted and nongifted children demonstrating emotional and behavioral risk, with parents and teachers identifying a higher number of boys and nongifted children as at risk. Among children demonstrating EBR, gifted children demonstrated elevated internalizing behaviors as rated by parents. Gifted students demonstrated higher academic performance regardless of risk level, suggesting higher cognitive abilities may be one of several protective factors that serve to attenuate the development of other social, emotional, or behavioral concerns. Implications for practice and future research needs are discussed.

  20. Performance scores in general practice: a comparison between the clinical versus medication-based approach to identify target populations.

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    Olivier Saint-Lary

    Full Text Available CONTEXT: From one country to another, the pay-for-performance mechanisms differ on one significant point: the identification of target populations, that is, populations which serve as a basis for calculating the indicators. The aim of this study was to compare clinical versus medication-based identification of populations of patients with diabetes and hypertension over the age of 50 (for men or 60 (for women, and any consequences this may have on the calculation of P4P indicators. METHODS: A comparative, retrospective, observational study was carried out with clinical and prescription data from a panel of general practitioners (GPs, the Observatory of General Medicine (OMG for the year 2007. Two indicators regarding the prescription for statins and aspirin in these populations were calculated. RESULTS: We analyzed data from 21.690 patients collected by 61 GPs via electronic medical files. Following the clinical-based approach, 2.278 patients were diabetic, 8,271 had hypertension and 1.539 had both against respectively 1.730, 8.511 and 1.304 following the medication-based approach (% agreement = 96%, kappa = 0.69. The main reasons for these differences were: forgetting to code the morbidities in the clinical approach, not taking into account the population of patients who were given life style and diet rules only or taking into account patients for whom morbidities other than hypertension could justify the use of antihypertensive drugs in the medication-based approach. The mean (confidence interval per doctor was 33.7% (31.5-35.9 for statin indicator and 38.4% (35.4-41.4 for aspirin indicator when the target populations were identified on the basis of clinical criteria whereas they were 37.9% (36.3-39.4 and 43.8% (41.4-46.3 on the basis of treatment criteria. CONCLUSION: The two approaches yield very "similar" scores but these scores cover different realities and offer food for thought on the possible usage of these indicators in the

  1. An integrated approach to identify the influential priority of the factors governing anaerobic H2 production by mixed cultures.

    Science.gov (United States)

    Fang, Fang; Zeng, Raymond J; Sheng, Guo-Ping; Yu, Han-Qing

    2010-05-01

    An integrated approach incorporating response surface methodology, grey relational entropy, and fuzzy analytic hierarchy process is established to prioritize the influence of main factors governing the anaerobic H(2) production process and their influential priority. Response surface methodology is employed to design experiments, and the grey relational entropy is used to evaluate the influential grade of the three input factors, i.e., pH, temperature and initial substrate concentration (S(ini)), on the H(2) yield, maximum H(2) production rate and volatile fatty acid yield. In addition, through a combination of grey relational entropy, fuzzy analytic hierarchy process, which is used to determine the weight, and accelerating genetic algorithm, which is employed to minimize the nonlinear function in fuzzy analytic hierarchy process, the overall H(2) production process performance could be comprehensively evaluated. The results show that pH is the most important factor influencing the yields of H(2) and volatile fatty acids, while S(ini) has the most significant effect on the maximum H(2) production rate. Compared to pH and S(ini), temperature has a less important effect on the overall H(2) production reactor performance. This approach provides an appropriate way to identify the influential priority of input factors and to evaluate the overall performance for the anaerobic H(2) production process, and it can also be used for other complex biological and non-biological wastewater treatment systems. PMID:20347115

  2. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  3. A Customizable Model for Chronic Disease Coordination: Lessons Learned From the Coordinated Chronic Disease Program.

    Science.gov (United States)

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-01-01

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managed resources, and 6) relationship building. These elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs. PMID:27032986

  4. A new experimental approach for studying bacterial genomic island evolution identifies island genes with bacterial host-specific expression patterns

    Directory of Open Access Journals (Sweden)

    Nickerson Cheryl A

    2006-01-01

    Full Text Available Abstract Background Genomic islands are regions of bacterial genomes that have been acquired by horizontal transfer and often contain blocks of genes that function together for specific processes. Recently, it has become clear that the impact of genomic islands on the evolution of different bacterial species is significant and represents a major force in establishing bacterial genomic variation. However, the study of genomic island evolution has been mostly performed at the sequence level using computer software or hybridization analysis to compare different bacterial genomic sequences. We describe here a novel experimental approach to study the evolution of species-specific bacterial genomic islands that identifies island genes that have evolved in such a way that they are differentially-expressed depending on the bacterial host background into which they are transferred. Results We demonstrate this approach by using a "test" genomic island that we have cloned from the Salmonella typhimurium genome (island 4305 and transferred to a range of Gram negative bacterial hosts of differing evolutionary relationships to S. typhimurium. Systematic analysis of the expression of the island genes in the different hosts compared to proper controls allowed identification of genes with genera-specific expression patterns. The data from the analysis can be arranged in a matrix to give an expression "array" of the island genes in the different bacterial backgrounds. A conserved 19-bp DNA site was found upstream of at least two of the differentially-expressed island genes. To our knowledge, this is the first systematic analysis of horizontally-transferred genomic island gene expression in a broad range of Gram negative hosts. We also present evidence in this study that the IS200 element found in island 4305 in S. typhimurium strain LT2 was inserted after the island had already been acquired by the S. typhimurium lineage and that this element is likely not

  5. Identifying (Quasi) Equally Informative Subsets in Feature Selection Problems for Classification: A Max-Relevance Min-Redundancy Approach.

    Science.gov (United States)

    Karakaya, Gulsah; Galelli, Stefano; Ahipasaoglu, Selin Damla; Taormina, Riccardo

    2016-06-01

    An emerging trend in feature selection is the development of two-objective algorithms that analyze the tradeoff between the number of features and the classification performance of the model built with these features. Since these two objectives are conflicting, a typical result stands in a set of Pareto-efficient subsets, each having a different cardinality and a corresponding discriminating power. However, this approach overlooks the fact that, for a given cardinality, there can be several subsets with similar information content. The study reported here addresses this problem, and introduces a novel multiobjective feature selection approach conceived to identify: 1) a subset that maximizes the performance of a given classifier and 2) a set of subsets that are quasi equally informative, i.e., have almost same classification performance, to the performance maximizing subset. The approach consists of a wrapper [Wrapper for Quasi Equally Informative Subset Selection (W-QEISS)] built on the formulation of a four-objective optimization problem, which is aimed at maximizing the accuracy of a classifier, minimizing the number of features, and optimizing two entropy-based measures of relevance and redundancy. This allows conducting the search in a larger space, thus enabling the wrapper to generate a large number of Pareto-efficient solutions. The algorithm is compared against the mRMR algorithm, a two-objective wrapper and a computationally efficient filter [Filter for Quasi Equally Informative Subset Selection (F-QEISS)] on 24 University of California, Irvine, (UCI) datasets including both binary and multiclass classification. Experimental results show that W-QEISS has the capability of evolving a rich and diverse set of Pareto-efficient solutions, and that their availability helps in: 1) studying the tradeoff between multiple measures of classification performance and 2) understanding the relative importance of each feature. The quasi equally informative subsets are

  6. A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Kendra A Williams

    2014-11-01

    Full Text Available Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP8247Ng/J (TRAMP mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ F2 intercross males (n = 228, which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322 were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2 harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such

  7. Model Validation Using Coordinate Distance with Performance Sensitivity

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    Jiann-Shiun Lew

    2008-01-01

    Full Text Available This paper presents an innovative approach to model validation for a structure with significant parameter variations. Model uncertainty of the structural dynamics is quantified with the use of a singular value decomposition technique to extract the principal components of parameter change, and an interval model is generated to represent the system with parameter uncertainty. The coordinate vector, corresponding to the identified principal directions, of the validation system is computed. The coordinate distance between the validation system and the identified interval model is used as a metric for model validation. A beam structure with an attached subsystem, which has significant parameter uncertainty, is used to demonstrate the proposed approach.

  8. Practically Coordinating

    OpenAIRE

    Durfee, Edmund H.

    1999-01-01

    To coordinate, intelligent agents might need to know something about themselves, about each other, about how others view themselves and others, about how others think others view themselves and others, and so on. Taken to an extreme, the amount of knowledge an agent might possess to coordinate its interactions with others might outstrip the agent's limited reasoning capacity (its available time, memory, and so on). Much of the work in studying and building multiagent systems has thus been dev...

  9. Biosensor-based approach identifies four distinct calmodulin-binding domains in the G protein-coupled estrogen receptor 1.

    Directory of Open Access Journals (Sweden)

    Quang-Kim Tran

    Full Text Available The G protein-coupled estrogen receptor 1 (GPER has been demonstrated to participate in many cellular functions, but its regulatory inputs are not clearly understood. Here we describe a new approach that identifies GPER as a calmodulin-binding protein, locates interaction sites, and characterizes their binding properties. GPER coimmunoprecipitates with calmodulin in primary vascular smooth muscle cells under resting conditions, which is enhanced upon acute treatment with either specific ligands or a Ca(2+-elevating agent. To confirm direct interaction and locate the calmodulin-binding domain(s, we designed a series of FRET biosensors that consist of enhanced cyan and yellow fluorescent proteins flanking each of GPER's submembrane domains (SMDs. Responses of these biosensors showed that all four submembrane domains directly bind calmodulin. Modifications of biosensor linker identified domains that display the strongest calmodulin-binding affinities and largest biosensor dynamics, including a.a. 83-93, 150-175, 242-259, 330-351, corresponding respectively to SMDs 1, 2, 3, and the juxta-membranous section of SMD4. These biosensors bind calmodulin in a strictly Ca(2+-dependent fashion and with disparate affinities in the order SMD2>SMD4>SMD3>SMD1, apparent K d values being 0.44 ± 0.03, 1.40 ± 0.16, 8.01 ± 0.29, and 136.62 ± 6.56 µM, respectively. Interestingly, simultaneous determinations of biosensor responses and suitable Ca(2+ indicators identified separate Ca(2+ sensitivities for their interactions with calmodulin. SMD1-CaM complexes display a biphasic Ca(2+ response, representing two distinct species (SMD1 sp1 and SMD1 sp2 with drastically different Ca(2+ sensitivities. The Ca(2+ sensitivities of CaM-SMDs interactions follow the order SMD1sp1>SMD4>SMD2>SMD1sp2>SMD3, EC50(Ca(2+ values being 0.13 ± 0.02, 0.75 ± 0.05, 2.38 ± 0.13, 3.71 ± 0.13, and 5.15 ± 0.25 µM, respectively. These data indicate that calmodulin may regulate GPER

  10. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2009-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified...... that should be addressed, so that fair information principles can be applied in the context of m-advertising. It also points out the limitations of these principles. Furthermore, the article discusses a range of models that is available for regulating the collection, use and disclosure of personal data...

  11. Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes

    Directory of Open Access Journals (Sweden)

    Abdul-Rahim Zainab S

    2011-03-01

    Full Text Available Abstract Background Women who develop gestational diabetes mellitus (GDM have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a barriers and facilitators to healthy lifestyle changes postpartum, and b specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program. Methods We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews. Results Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify. Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered

  12. Advances in the Kepler Transit Search Engine and Automated Approaches to Identifying Likely Planet Candidates in Transit Surveys

    Science.gov (United States)

    Jenkins, Jon Michael

    2015-08-01

    Twenty years ago, no planets were known outside our own solar system. Since then, the discoveries of ~1500 exoplanets have radically altered our views of planets and planetary systems. This revolution is due in no small part to the Kepler Mission, which has discovered >1000 of these planets and >4000 planet candidates. While Kepler has shown that small rocky planets and planetary systems are quite common, the quest to find Earth’s closest cousins and characterize their atmospheres presses forward with missions such as NASA Explorer Program’s Transiting Exoplanet Survey Satellite (TESS) slated for launch in 2017 and ESA’s PLATO mission scheduled for launch in 2024.These future missions pose daunting data processing challenges in terms of the number of stars, the amount of data, and the difficulties in detecting weak signatures of transiting small planets against a roaring background. These complications include instrument noise and systematic effects as well as the intrinsic stellar variability of the subjects under scrutiny. In this paper we review recent developments in the Kepler transit search pipeline improving both the yield and reliability of detected transit signatures.Many of the phenomena in light curves that represent noise can also trigger transit detection algorithms. The Kepler Mission has expended great effort in suppressing false positives from its planetary candidate catalogs. While over 18,000 transit-like signatures can be identified for a search across 4 years of data, most of these signatures are artifacts, not planets. Vetting all such signatures historically takes several months’ effort by many individuals. We describe the application of machine learning approaches for the automated vetting and production of planet candidate catalogs. These algorithms can improve the efficiency of the human vetting effort as well as quantifying the likelihood that each candidate is truly a planet. This information is crucial for obtaining valid planet

  13. Identifying tree crown delineation shapes and need for remediation on high resolution imagery using an evidence based approach

    Science.gov (United States)

    Leckie, Donald G.; Walsworth, Nicholas; Gougeon, François A.

    2016-04-01

    In order to fully realize the benefits of automated individual tree mapping for tree species, health, forest inventory attribution and forest management decision making, the tree delineations should be as good as possible. The concept of identifying poorly delineated tree crowns and suggesting likely types of remediation was investigated. Delineations (isolations or isols) were classified into shape types reflecting whether they were realistic tree shapes and the likely kind of remediation needed. Shape type was classified by an evidence based rules approach using primitives based on isol size, shape indices, morphology, the presence of local maxima, and matches with template models representing trees of different sizes. A test set containing 50,000 isols based on an automated tree delineation of 40 cm multispectral airborne imagery of a diverse temperate-boreal forest site was used. Isolations representing single trees or several trees were the focus, as opposed to cases where a tree is split into several isols. For eight shape classes from regular through to convolute, shape classification accuracy was in the order of 62%; simplifying to six classes accuracy was 83%. Shape type did give an indication of the type of remediation and there were 6% false alarms (i.e., isols classed as needing remediation but did not). Alternately, there were 5% omissions (i.e., isols of regular shape and not earmarked for remediation that did need remediation). The usefulness of the concept of identifying poor delineations in need of remediation was demonstrated and one suite of methods developed and shown to be effective.

  14. A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2006-11-01

    Full Text Available Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.

  15. FINDSITE(X): a structure-based, small molecule virtual screening approach with application to all identified human GPCRs.

    Science.gov (United States)

    Zhou, Hongyi; Skolnick, Jeffrey

    2012-06-01

    We have developed FINDSITE(X), an extension of FINDSITE, a protein threading based algorithm for the inference of protein binding sites, biochemical function and virtual ligand screening, that removes the limitation that holo protein structures (those containing bound ligands) of a sufficiently large set of distant evolutionarily related proteins to the target be solved; rather, predicted protein structures and experimental ligand binding information are employed. To provide the predicted protein structures, a fast and accurate version of our recently developed TASSER(VMT), TASSER(VMT)-lite, for template-based protein structural modeling applicable up to 1000 residues is developed and tested, with comparable performance to the top CASP9 servers. Then, a hybrid approach that combines structure alignments with an evolutionary similarity score for identifying functional relationships between target and proteins with binding data has been developed. By way of illustration, FINDSITE(X) is applied to 998 identified human G-protein coupled receptors (GPCRs). First, TASSER(VMT)-lite provides updates of all human GPCR structures previously modeled in our lab. We then use these structures and the new function similarity detection algorithm to screen all human GPCRs against the ZINC8 nonredundant (TC identity > 30% to the target from the binding data library) on a 168 human GPCR set with known binding data, the average enrichment factor in the top 1% of the compound library (EF(0.01)) is 22.7, whereas EF(0.01) by FINDSITE is 7.1. For virtual screening when just the target and its native ligands are excluded, the average EF(0.01) reaches 41.4. We also analyze off-target interactions for the 168 protein test set. All predicted structures, virtual screening data and off-target interactions for the 998 human GPCRs are available at http://cssb.biology.gatech.edu/skolnick/webservice/gpcr/index.html .

  16. Use of a Machine Learning-Based High Content Analysis Approach to Identify Photoreceptor Neurite Promoting Molecules.

    Science.gov (United States)

    Fuller, John A; Berlinicke, Cynthia A; Inglese, James; Zack, Donald J

    2016-01-01

    High content analysis (HCA) has become a leading methodology in phenotypic drug discovery efforts. Typical HCA workflows include imaging cells using an automated microscope and analyzing the data using algorithms designed to quantify one or more specific phenotypes of interest. Due to the richness of high content data, unappreciated phenotypic changes may be discovered in existing image sets using interactive machine-learning based software systems. Primary postnatal day four retinal cells from the photoreceptor (PR) labeled QRX-EGFP reporter mice were isolated, seeded, treated with a set of 234 profiled kinase inhibitors and then cultured for 1 week. The cells were imaged with an Acumen plate-based laser cytometer to determine the number and intensity of GFP-expressing, i.e. PR, cells. Wells displaying intensities and counts above threshold values of interest were re-imaged at a higher resolution with an INCell2000 automated microscope. The images were analyzed with an open source HCA analysis tool, PhenoRipper (Rajaram et al., Nat Methods 9:635-637, 2012), to identify the high GFP-inducing treatments that additionally resulted in diverse phenotypes compared to the vehicle control samples. The pyrimidinopyrimidone kinase inhibitor CHEMBL-1766490, a pan kinase inhibitor whose major known targets are p38α and the Src family member lck, was identified as an inducer of photoreceptor neuritogenesis by using the open-source HCA program PhenoRipper. This finding was corroborated using a cell-based method of image analysis that measures quantitative differences in the mean neurite length in GFP expressing cells. Interacting with data using machine learning algorithms may complement traditional HCA approaches by leading to the discovery of small molecule-induced cellular phenotypes in addition to those upon which the investigator is initially focusing.

  17. The chart based approach to studying the global structure of a spacetime induces a coordinate invariant boundary

    CERN Document Server

    Whale, Ben

    2014-01-01

    I demonstrate that the chart based approach to the study of the global structure of Lorentzian manifolds induces a homeomorphism of the manifold into a topological space as an open dense set. The topological boundary of this homeomorphism is a chart independent boundary of ideal points equipped with a topological structure and a physically motivated classification. I show that this new boundary contains all other boundaries that can be presented as the topological boundary of an envelopment. Hence, in particular, it is a generalisation of Penrose's conformal boundary. I provide three detailed examples: the conformal compactification of Minkowski spacetime, Scott and Szekeres' analysis of the Curzon singularity and Beyer and Hennig's analysis of smooth Gowdy symmetric generalised Taub-NUT spacetimes.

  18. A SURVEY ON COMPUTATIONAL APPROACHES TO IDENTIFY MICRORNA%计算方法预测microRNA研究进展

    Institute of Scientific and Technical Information of China (English)

    万琳霞; 丁建栋; 关佶红

    2012-01-01

    microRNA(miRNA)是一类内源性、长度为19-24个碱基的非编码小分子RNA.它在调控动植物的基因表达、生长发育等方面起着重要的作用.现阶段寻找miRNA 的方法主要分为实验方法和计算预测两大类,其中,实验的方法很难测定表达量偏低或者特异表达的miRNA,也不适合进行基因组范围的发现.而计算预测的方法则恰好可以弥补这些不足.总结近几年计算预测miRNA的方法,归纳为三类,分别是基于同源性比较的方法、基于机器学习的方法和基于高通量测序的方法.最后对miRNA 计算预测方法未来的发展方向作出了探讨.%microRNAs (miRNAB) are small non-coding RNAs about 19 to 24 nucleotides in length. They play a key role in gene regulation of animals and plants. Currently, there' re mainly two different types of approaches to identify miRNAs, one is experimental, the other is computational. Experimental methods are usually incapable of detecting miRNAs that have low expression levels or are expressed tissue-specifically whereas computational approaches can overcome such disadvantage. The article presents an overview of computational approaches proposed for miRNA identification, which can be grouped into three categories: homology methods, machine learning methods and deep sequencing methods. In the end, the article expresses some opinions about the potential trend of miRNA identification.

  19. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

    Science.gov (United States)

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  20. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches.

    Science.gov (United States)

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  1. A System-Wide Approach to Identify the Mechanisms of Barnacle Attachment: Toward the Discovery of New Antifouling Compounds

    KAUST Repository

    Al-Aqeel, Sarah

    2015-11-01

    Biofouling is a significant economic problem, particularly for marine and offshore oil industries. The acorn barnacle (Amphibalanus (Balanus) amphitrite) is the main biofouling organism in marine environments. Environmental conditions, the physiology of the biofouling organism, the surrounding microbial community, and the properties of the substratum can all influence the attachment of biofouling organisms to substrates. My dissertation investigated the biological processes involved in B. amphitrite development and attachment in the unique environment of the Red Sea, where the average water surface temperature is 34°C and the salinity reaches 41‰. I profiled the transcriptome and proteome of B. amphitrite at different life stages (nauplius II, nauplius VI, and cyprid) and identified 65,784 expressed contigs and 1387 expressed proteins by quantitative proteomics. During the planktonic stage, genes related to osmotic stress, salt stress, the hyperosmotic response, and the Wnt signaling pathway were strongly up-regulated, hereas genes related to the MAPK pathway, lipid metabolism, and cuticle development were down-regulated. In the transition from the nauplius VI to cyprid stages, there was up-regulation of genes involved in blood coagulation, cuticle development, and eggshell formation, and down-regulation of genes in the nitric oxide pathway, which stimulates the swimming and feeding responses of marine invertebrates. This system-wide integrated approach elucidated the development and attachment pathways important in B. amphitrite. Enzymes and metabolites in these pathways are potential molecular targets for the development of new antifouling compounds.

  2. A novel labeling approach identifies three stability levels of acetylcholine receptors in the mouse neuromuscular junction in vivo.

    Directory of Open Access Journals (Sweden)

    Siegfried Strack

    Full Text Available BACKGROUND: The turnover of acetylcholine receptors at the neuromuscular junction is regulated in an activity-dependent manner. Upon denervation and under various other pathological conditions, receptor half-life is decreased. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate a novel approach to follow the kinetics of acetylcholine receptor lifetimes upon pulse labeling of mouse muscles with ¹²⁵I-α-bungarotoxin in vivo. In contrast to previous assays where residual activity was measured ex vivo, in our setup the same animals are used throughout the whole measurement period, thereby permitting a dramatic reduction of animal numbers at increased data quality. We identified three stability levels of acetylcholine receptors depending on the presence or absence of innervation: one pool of receptors with a long half-life of ∼13 days, a second with an intermediate half-life of ∼8 days, and a third with a short half-life of ∼1 day. Data were highly reproducible from animal to animal and followed simple exponential terms. The principal outcomes of these measurements were reproduced by an optical pulse-labeling assay introduced recently. CONCLUSIONS/SIGNIFICANCE: A novel assay to determine kinetics of acetylcholine receptor turnover with small animal numbers is presented. Our data show that nerve activity acts on muscle acetylcholine receptor stability by at least two different means, one shifting receptor lifetime from short to intermediate and another, which further increases receptor stability to a long lifetime. We hypothesize on possible molecular mechanisms.

  3. 7 CFR 22.201 - Coordination.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Coordination. 22.201 Section 22.201 Agriculture Office of the Secretary of Agriculture RURAL DEVELOPMENT COORDINATION Roles and Responsibilities of Federal Government § 22.201 Coordination. The following identifies types and levels of coordination: (a)...

  4. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Zhou Jing

    2011-04-01

    Full Text Available Abstract Background Autosomal dominant polycystic kidney disease (ADPKD is characterized by cyst formation throughout the kidney parenchyma. It is caused by mutations in either of two genes, PKD1 and PKD2. Mice that lack functional Pkd1 (Pkd1-/-, develop rapidly progressive cystic disease during embryogenesis, and serve as a model to study human ADPKD. Genome wide transcriptome reprogramming and the possible roles of micro-RNAs (miRNAs that affect the initiation and progression of cyst formation in the Pkd1-/- have yet to be studied. miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD. Results We examined the molecular pathways that modulate renal cyst formation and growth in the Pkd1-/- model by performing global gene-expression profiling in embryonic kidneys at days 14.5 and 17.5. Gene Ontology and gene set enrichment analysis were used to identify overrepresented signaling pathways in Pkd1-/- kidneys. We found dysregulation of developmental, metabolic, and signaling pathways (e.g. Wnt, calcium, TGF-β and MAPK in Pkd1-/- kidneys. Using a comparative transcriptomics approach, we determined similarities and differences with human ADPKD: ~50% overlap at the pathway level among the mis-regulated pathways was observed. By using computational approaches (TargetScan, miRanda, microT and miRDB, we then predicted miRNAs that were suggested to target the differentially expressed mRNAs. Differential expressions of 9 candidate miRNAs, miRs-10a, -30a-5p, -96, -126-5p, -182, -200a, -204, -429 and -488, and 16 genes were confirmed by qPCR. In addition, 14 candidate miRNA:mRNA reciprocal interactions were predicted. Several of the highly regulated genes and pathways were predicted as targets of miRNAs. Conclusions We have described global transcriptional reprogramming during the progression of PKD in

  5. Truth concealed behind "Zero Increase of Total Water Use" and coordination approach of socio-economic and eco-environmental water uses in the Weihe River Basin, China

    Science.gov (United States)

    Jia, Y.; Wei, N.; Hao, C.; You, J.; Niu, C.; Qiu, Y.

    2014-09-01

    The water resources situation in the water-stressed Weihe River Basin, China, is more serious now than ever before because of a decrease in water resources and socio-economic development. A "Zero increase of socio-economic water use" in recent years gives people a wrong understanding and conceals the water crisis in the basin because the socio-economic water consumption has actually increased. Water use for the hydro-ecological system has been greatly reduced by a decrease in water resources and socio-economic water consumption increase. New concepts of hierarchical water uses for every sector and water consumption control are suggested for coordinating water uses of the socio-economy and ecosystems in the water-stressed basin. The traditional water resources allocation and regulation in China usually set up a priority sequence for water use sectors. Generally speaking, domestic water use has the highest priority and a highest guarantee rate, followed by industrial water use, irrigation and lastly ecological water use. The concept of hierarchical water use for every sector is to distinguish the water use of every sector into minimum part, appropriate part, and expected extra part with different guarantee rates, and the minimum parts of all sectors should be first guaranteed. By applying a water allocation model, we compared the water allocation results of the traditional approach and the newly suggested approach. Although further study is desired, the results are believed to be of an important referential value to sustainable development in the basin.

  6. A microarray approach to identify genes involved in seed-pericarp cross-talk and development in peach

    Directory of Open Access Journals (Sweden)

    Zaffalon Valerio

    2011-06-01

    Full Text Available Abstract Background Field observations and a few physiological studies have demonstrated that peach embryogenesis and fruit development are tightly coupled. In fact, attempts to stimulate parthenocarpic fruit development by means of external tools have failed. Moreover, physiological disturbances during early embryo development lead to seed abortion and fruitlet abscission. Later in embryo development, the interactions between seed and fruit development become less strict. As there is limited genetic and molecular information about seed-pericarp cross-talk and development in peach, a massive gene approach based on the use of the μPEACH 1.0 array platform and quantitative real time RT-PCR (qRT-PCR was used to study this process. Results A comparative analysis of the transcription profiles conducted in seed and mesocarp (cv Fantasia throughout different developmental stages (S1, S2, S3 and S4 evidenced that 455 genes are differentially expressed in seed and fruit. Among differentially expressed genes some were validated as markers in two subsequent years and in three different genotypes. Seed markers were a LTP1 (lipid transfer protein, a PR (pathogenesis-related protein, a prunin and LEA (Late Embryogenesis Abundant protein, for S1, S2, S3 and S4, respectively. Mesocarp markers were a RD22-like protein, a serin-carboxypeptidase, a senescence related protein and an Aux/IAA, for S1, S2, S3 and S4, respectively. The microarray data, analyzed by using the HORMONOMETER platform, allowed the identification of hormone-responsive genes, some of them putatively involved in seed-pericarp crosstalk. Results indicated that auxin, cytokinins, and gibberellins are good candidates, acting either directly (auxin or indirectly as signals during early development, when the cross-talk is more active and vital for fruit set, whereas abscisic acid and ethylene may be involved later on. Conclusions In this research, genes were identified marking different phases of

  7. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Science.gov (United States)

    Abram, Nicola K; MacMillan, Douglas C; Xofis, Panteleimon; Ancrenaz, Marc; Tzanopoulos, Joseph; Ong, Robert; Goossens, Benoit; Koh, Lian Pin; Del Valle, Christian; Peter, Lucy; Morel, Alexandra C; Lackman, Isabelle; Chung, Robin; Kler, Harjinder; Ambu, Laurentius; Baya, William; Knight, Andrew T

    2016-01-01

    + competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds.

  8. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach

    Science.gov (United States)

    MacMillan, Douglas C.; Xofis, Panteleimon; Ancrenaz, Marc; Tzanopoulos, Joseph; Ong, Robert; Goossens, Benoit; Koh, Lian Pin; Del Valle, Christian; Peter, Lucy; Morel, Alexandra C.; Lackman, Isabelle; Chung, Robin; Kler, Harjinder; Ambu, Laurentius; Baya, William; Knight, Andrew T.

    2016-01-01

    + competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds. PMID:27276218

  9. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Science.gov (United States)

    Abram, Nicola K; MacMillan, Douglas C; Xofis, Panteleimon; Ancrenaz, Marc; Tzanopoulos, Joseph; Ong, Robert; Goossens, Benoit; Koh, Lian Pin; Del Valle, Christian; Peter, Lucy; Morel, Alexandra C; Lackman, Isabelle; Chung, Robin; Kler, Harjinder; Ambu, Laurentius; Baya, William; Knight, Andrew T

    2016-01-01

    + competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds. PMID:27276218

  10. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Directory of Open Access Journals (Sweden)

    Nicola K Abram

    : highlighting REDD+ competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds.

  11. Coordinated unbundling

    DEFF Research Database (Denmark)

    Timmermans, Bram; Zabala-Iturriagagoitia, Jon Mikel

    2013-01-01

    not focused on the role this policy instrument can play in the promotion of (knowledge-intensive) entrepreneurship. This paper investigates this link in more detail and introduces the concept of coordinated unbundling as a strategy that can facilitate this purpose. We also present a framework on how...

  12. Connecting the Disconnected: Social Work and Social Network Analysis. A Methodological Approach to Identifying Network Peer Leaders

    Directory of Open Access Journals (Sweden)

    del Fresno García, Miguel

    2015-02-01

    Full Text Available Social network theory and analysis (SNA offers a useful conceptual framework and a robust set of methods for understanding, analysing, and representing the pattern of social interactions that surround individuals forming an overall network of ties. SNA provides both insights and applications regarding relational structures that may be consequential for individual and collective agency. Despite the fact that both SNA and social work focus on relationships and behaviour, and that each discipline could substantively inform the other, there remains a significant lack of intersection between the two disciplines. In response to this gap, SNA applied to social work can provide additional ways to both diagnose and intervene behaviourally through the following approaches: a by identifying key players in promoting the dissemination of behavioral changes in networks; b by segmenting and identifying groups, cliques and communities; c by supporting behavioural change through social ties surrounding the individual; and d by aligning and applying specific interventions that draw on mutually interactive processes in terms of individual influences on networks, as well as network influences on individuals. SNA provides social work with an additional lens and set of tools based on the constellation of interactions surrounding individuals, families, groups or communities that supports understanding, diagnosis, and intervention.La Teoría y Análisis de Redes Sociales (SNA ofrece un conjunto de métodos de análisis de las interacciones sociales de los seres humanos, que permiten de forma específica investigar las estructuras relacionales y la representación de éstas como redes. SNA proporciona tanto acceso a nuevo conocimiento como la representación de las estructuras relacionales y como éstas pueden ser consecuencia de la acción individual y colectiva. A pesar de que tanto el SNA como el Trabajo Social tienen su foco en las relaciones y el comportamiento, de

  13. Data mining approach identifies research priorities and data requirements for resolving the red algal tree of life

    Directory of Open Access Journals (Sweden)

    Yoon Hwan

    2010-01-01

    Full Text Available Abstract Background The assembly of the tree of life has seen significant progress in recent years but algae and protists have been largely overlooked in this effort. Many groups of algae and protists have ancient roots and it is unclear how much data will be required to resolve their phylogenetic relationships for incorporation in the tree of life. The red algae, a group of primary photosynthetic eukaryotes of more than a billion years old, provide the earliest fossil evidence for eukaryotic multicellularity and sexual reproduction. Despite this evolutionary significance, their phylogenetic relationships are understudied. This study aims to infer a comprehensive red algal tree of life at the family level from a supermatrix containing data mined from GenBank. We aim to locate remaining regions of low support in the topology, evaluate their causes and estimate the amount of data required to resolve them. Results Phylogenetic analysis of a supermatrix of 14 loci and 98 red algal families yielded the most complete red algal tree of life to date. Visualization of statistical support showed the presence of five poorly supported regions. Causes for low support were identified with statistics about the age of the region, data availability and node density, showing that poor support has different origins in different parts of the tree. Parametric simulation experiments yielded optimistic estimates of how much data will be needed to resolve the poorly supported regions (ca. 103 to ca. 104 nucleotides for the different regions. Nonparametric simulations gave a markedly more pessimistic image, some regions requiring more than 2.8 105 nucleotides or not achieving the desired level of support at all. The discrepancies between parametric and nonparametric simulations are discussed in light of our dataset and known attributes of both approaches. Conclusions Our study takes the red algae one step closer to meaningful inclusion in the tree of life. In addition

  14. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    Overview From a technical perspective, CMS has been in “beam operation” state since 6th November. The detector is fully closed with all components operational and the magnetic field is normally at the nominal 3.8T. The UXC cavern is normally closed with the radiation veto set. Access to UXC is now only possible during downtimes of LHC. Such accesses must be carefully planned, documented and carried out in agreement with CMS Technical Coordination, Experimental Area Management, LHC programme coordination and the CCC. Material flow in and out of UXC is now strictly controlled. Access to USC remains possible at any time, although, for safety reasons, it is necessary to register with the shift crew in the control room before going down.It is obligatory for all material leaving UXC to pass through the underground buffer zone for RP scanning, database entry and appropriate labeling for traceability. Technical coordination (notably Stephane Bally and Christoph Schaefer), the shift crew and run ...

  15. A novel approach to identify optimal metabotypes of elongase and desaturase activities in prevention of acute coronary syndrome

    Science.gov (United States)

    Both metabolomic and genomic approaches are valuable for risk analysis, however typical approaches evaluating differences in means do not model the changes well. Gene polymorphisms that alter function would appear as distinct populations, or metabotypes, from the predominant one, in which case risk...

  16. Identifying interactions in the time and frequency domains in local and global networks - A Granger Causality Approach

    Directory of Open Access Journals (Sweden)

    Guo Shuixia

    2010-06-01

    Full Text Available Abstract Background Reverse-engineering approaches such as Bayesian network inference, ordinary differential equations (ODEs and information theory are widely applied to deriving causal relationships among different elements such as genes, proteins, metabolites, neurons, brain areas and so on, based upon multi-dimensional spatial and temporal data. There are several well-established reverse-engineering approaches to explore causal relationships in a dynamic network, such as ordinary differential equations (ODE, Bayesian networks, information theory and Granger Causality. Results Here we focused on Granger causality both in the time and frequency domain and in local and global networks, and applied our approach to experimental data (genes and proteins. For a small gene network, Granger causality outperformed all the other three approaches mentioned above. A global protein network of 812 proteins was reconstructed, using a novel approach. The obtained results fitted well with known experimental findings and predicted many experimentally testable results. In addition to interactions in the time domain, interactions in the frequency domain were also recovered. Conclusions The results on the proteomic data and gene data confirm that Granger causality is a simple and accurate approach to recover the network structure. Our approach is general and can be easily applied to other types of temporal data.

  17. How Can Agile Practices Minimize Global Software Development Co-ordination Risks?

    Science.gov (United States)

    Hossain, Emam; Babar, Muhammad Ali; Verner, June

    The distribution of project stakeholders in Global Software Development (GSD) projects provides significant risks related to project communication, coordination and control processes. There is growing interest in applying agile practices in GSD projects in order to leverage the advantages of both approaches. In some cases, GSD project managers use agile practices to reduce project distribution challenges. We use an existing coordination framework to identify GSD coordination problems due to temporal, geographical and socio-cultural distances. An industry-based case study is used to describe, explore and explain the use of agile practices to reduce development coordination challenges.

  18. To Be or Not to Be Associated: Power study of four statistical modeling approaches to identify parasite associations in cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Elise eVaumourin

    2014-05-01

    Full Text Available A growing number of studies are reporting simultaneous infections by parasites in many different hosts. The detection of whether these parasites are significantly associated is important in medicine and epidemiology. Numerous approaches to detect associations are available, but only a few provide statistical tests. Furthermore, they generally test for an overall detection of association and do not identify which parasite is associated with which other one. Here, we developed a new approach, the association screening approach, to detect the overall and the detail of multi-parasite associations. We studied the power of this new approach and of three other known ones (i.e. the generalized chi-square, the network and the multinomial GLM approaches to identify parasite associations either due to parasite interactions or to confounding factors. We applied these four approaches to detect associations within two populations of multi-infected hosts: 1 rodents infected with Bartonella sp., Babesia microti and Anaplasma phagocytophilum and 2 bovine population infected with Theileria sp. and Babesia sp.. We found that the best power is obtained with the screening model and the generalized chi-square test. The differentiation between associations, which are due to confounding factors and parasite interactions was not possible. The screening approach significantly identified associations between Bartonella doshiae and B. microti, and between T. parva, T. mutans and T. velifera. Thus, the screening approach was relevant to test the overall presence of parasite associations and identify the parasite combinations that are significantly over- or under-represented. Unravelling whether the associations are due to real biological interactions or confounding factors should be further investigated. Nevertheless, in the age of genomics and the advent of new technologies, it is a considerable asset to speed up researches focusing on the mechanisms driving interactions

  19. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    2010-01-01

    Operational Experience At the end of the first full-year running period of LHC, CMS is established as a reliable, robust and mature experiment. In particular common systems and infrastructure faults accounted for <0.6 % CMS downtime during LHC pp physics. Technical operation throughout the entire year was rather smooth, the main faults requiring UXC access being sub-detector power systems and rack-cooling turbines. All such problems were corrected during scheduled technical stops, in the shadow of tunnel access needed by the LHC, or in negotiated accesses or access extensions. Nevertheless, the number of necessary accesses to the UXC averaged more than one per week and the technical stops were inevitably packed with work packages, typically 30 being executed within a few days, placing a high load on the coordination and area management teams. It is an appropriate moment for CMS Technical Coordination to thank all those in many CERN departments and in the Collaboration, who were involved in CMS techni...

  20. Identifying Effective Pedagogical Approaches for Online Workplace Training: A case study of the South African wood products manufacturing sector

    Directory of Open Access Journals (Sweden)

    Ian S. Macdonald

    2007-11-01

    Full Text Available This study investigated appropriate pedagogical techniques for workplace e-learning programs in the South African wood products (furniture manufacturing sector. The study found that learners responded favourably to constructivist teaching approaches, such as asynchronous discussions, open-ended task-based activities, and assignments incorporating authentic, real-world examples. Learners viewed constructivist activities to be more useful than quizzes and traditional essay-based assignments, as they allowed new concepts to be learned in context and were perceived to promote deeper understanding of the subject matter. Nevertheless, they valued the inclusion of a blend of pedagogical approaches in the course design, as this enabled them to approach and analyze new concepts in an assortment of ways. Learners placed importance on regular interaction with other learners and course instructors, and were strongly in favour of including face-to-face components in Web-based courses.

  1. Mapping industrial networks as an approach to identify inter-organisational collaborative potential in new product development

    DEFF Research Database (Denmark)

    Parraguez, Pedro; Maier, Anja

    2012-01-01

    Increased industrial complexity and specialization is pushing organizations to participate more proactively in collaborative networks. These networks enable them to create new products and services requiring a pool of knowledge and capabilities going beyond the traditional organizational boundaries....... Consequently, identifying and selecting potential partners to establish collaboration agreements can be a key activity in the new product development process. This paper explores the implications of mapping industrial networks with the purpose of identifying inter-organisational collaborative potential....... The analysis is contextualized mapping the Danish Cleantech industry and depict the uses of the visualization and analysis of industrial networks in the selection of co-developing partners....

  2. A Quantitative Mass Spectrometry-based Approach for Identifying Protein Kinase-Clients and Quantifying Kinase Activity

    Science.gov (United States)

    The Homo sapiens and Arabidopsis thaliana genomes are believed to encode >500 and >1,000 protein kinases, respectively. Despite this abundance, few bona fide kinase-client relationships have been described in detail. Mass spectrometry (MS)-based approaches have been integral to the large-scale mapp...

  3. Identifying Multi-Level Culturally Appropriate Smoking Cessation Strategies for Aboriginal Health Staff: A Concept Mapping Approach

    Science.gov (United States)

    Dawson, Anna P.; Cargo, Margaret; Stewart, Harold; Chong, Alwin; Daniel, Mark

    2013-01-01

    Aboriginal Australians, including Aboriginal Health Workers (AHWs), smoke at rates double the non-Aboriginal population. This study utilized concept mapping methodology to identify and prioritize culturally relevant strategies to promote smoking cessation in AHWs. Stakeholder participants included AHWs, other health service employees and tobacco…

  4. Co-activation Probability Estimation (CoPE): An approach for modeling functional co-activation architecture based on neuroimaging coordinates.

    Science.gov (United States)

    Chu, Congying; Fan, Lingzhong; Eickhoff, Claudia R; Liu, Yong; Yang, Yong; Eickhoff, Simon B; Jiang, Tianzi

    2015-08-15

    Recent progress in functional neuroimaging has prompted studies of brain activation during various cognitive tasks. Coordinate-based meta-analysis has been utilized to discover the brain regions that are consistently activated across experiments. However, within-experiment co-activation relationships, which can reflect the underlying functional relationships between different brain regions, have not been widely studied. In particular, voxel-wise co-activation, which may be able to provide a detailed configuration of the co-activation network, still needs to be modeled. To estimate the voxel-wise co-activation pattern and deduce the co-activation network, a Co-activation Probability Estimation (CoPE) method was proposed to model within-experiment activations for the purpose of defining the co-activations. A permutation test was adopted as a significance test. Moreover, the co-activations were automatically separated into local and long-range ones, based on distance. The two types of co-activations describe distinct features: the first reflects convergent activations; the second represents co-activations between different brain regions. The validation of CoPE was based on five simulation tests and one real dataset derived from studies of working memory. Both the simulated and the real data demonstrated that CoPE was not only able to find local convergence but also significant long-range co-activation. In particular, CoPE was able to identify a 'core' co-activation network in the working memory dataset. As a data-driven method, the CoPE method can be used to mine underlying co-activation relationships across experiments in future studies. PMID:26037052

  5. Coordination Capacity

    CERN Document Server

    Cuff, Paul; Cover, Thomas

    2009-01-01

    We develop elements of a theory of cooperation and coordination in networks. Rather than considering a communication network as a means of distributing information, or of reconstructing random processes at remote nodes, we ask what dependence can be established among the nodes given the communication constraints. Specifically, in a network with communication rates between the nodes, we ask what is the set of all achievable joint distributions p(x1, ..., xm) of actions at the nodes on the network. Several networks are solved, including arbitrarily large cascade networks. Distributed cooperation can be the solution to many problems such as distributed games, distributed control, and establishing mutual information bounds on the influence of one part of a physical system on another.

  6. Telling Our Story: A Narrative Therapy Approach to Helping Lesbian, Gay, Bisexual and Transgender People with a Learning Disability Identify and Strengthen Positive Self-identity Stories

    Science.gov (United States)

    Elderton, Anna; Clarke, Sally; Jones, Chris; Stacey, James

    2014-01-01

    Historically, and to a somewhat lesser extent presently, people with learning disabilities have had little or no voice in the stories other people (particularly professionals) tell about them and their lives. Four psychology workshops, based on a narrative therapy approach, were run for a group of people with learning disabilities who identify as…

  7. A RNA-seq approach to identify putative toxins from acrorhagi in aggressive and non-aggressive Anthopleura elegantissima polyps

    OpenAIRE

    Macrander, Jason; Mercer R Brugler; Daly, Marymegan

    2015-01-01

    Background The use of venom in intraspecific aggression is uncommon and venom-transmitting structures specifically used for intraspecific competition are found in few lineages of venomous taxa. Next-generation transcriptome sequencing allows robust characterization of venom diversity and exploration of functionally unique tissues. Using a tissue-specific RNA-seq approach, we investigate the venom composition and gene ontology diversity of acrorhagi, specialized structures used in intraspecifi...

  8. Identifying Effective Pedagogical Approaches for Online Workplace Training: A case study of the South African wood products manufacturing sector

    OpenAIRE

    Macdonald, Ian S.; Mark Bullen; R. A. Kozak

    2007-01-01

    This study investigated appropriate pedagogical techniques for workplace e-learning programs in the South African wood products (furniture) manufacturing sector. The study found that learners responded favourably to constructivist teaching approaches, such as asynchronous discussions, open-ended task-based activities, and assignments incorporating authentic, real-world examples. Learners viewed constructivist activities to be more useful than quizzes and traditional essay-based assignments, a...

  9. An entropy-based input variable selection approach to identify equally informative subsets for data-driven hydrological models

    Science.gov (United States)

    Karakaya, Gulsah; Taormina, Riccardo; Galelli, Stefano; Damla Ahipasaoglu, Selin

    2015-04-01

    Input Variable Selection (IVS) is an essential step in hydrological modelling problems, since it allows determining the optimal subset of input variables from a large set of candidates to characterize a preselected output. Interestingly, most of the existing IVS algorithms select a single subset, or, at most, one subset of input variables for each cardinality level, thus overlooking the fact that, for a given cardinality, there can be several subsets with similar information content. In this study, we develop a novel IVS approach specifically conceived to account for this issue. The approach is based on the formulation of a four-objective optimization problem that aims at minimizing the number of selected variables and maximizing the prediction accuracy of a data-driven model, while optimizing two entropy-based measures of relevance and redundancy. The redundancy measure ensures that the cross-dependence between the variables in a subset is minimized, while the relevance measure guarantees that the information content of each subset is maximized. In addition to the capability of selecting equally informative subsets, the approach is characterized by two other properties, namely 1) the capability of handling nonlinear interactions between the candidate input variables and preselected output, and 2) computational efficiency. These properties are guaranteed by the adoption of Extreme Learning Machine and Borg MOEA as data-driven model and heuristic optimization procedure, respectively. The approach is demonstrated on a long-term streamflow prediction problem, with the input dataset including both hydro-meteorological variables and climate indices representing dominant modes of climate variability. Results show that the availability of several equally informative subsets allows 1) determining the relative importance of each candidate input, thus supporting the understanding of the underlying physical processes, and 2) finding a better trade-off between multiple

  10. A Dual Infection Pseudorabies Virus Conditional Reporter Approach to Identify Projections to Collateralized Neurons in Complex Neural Circuits

    OpenAIRE

    J Patrick Card; Oren Kobiler; Ludmir, Ethan B.; Vedant Desai; Sved, Alan F.; Enquist, Lynn W.

    2011-01-01

    Replication and transneuronal transport of pseudorabies virus (PRV) are widely used to define the organization of neural circuits in rodent brain. Here we report a dual infection approach that highlights connections to neurons that collateralize within complex networks. The method combines Cre recombinase (Cre) expression from a PRV recombinant (PRV-267) and Cre-dependent reporter gene expression from a second infecting strain of PRV (PRV-263). PRV-267 expresses both Cre and a monomeric red f...

  11. An Integrated Approach Identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated Genes in Developing Cerebellum and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2008-01-01

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.

  12. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments

    OpenAIRE

    Min Zhao; Lei Kong; Hong Qu

    2014-01-01

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X...

  13. A Microbial Signature Approach to Identify Fecal Pollution in the Waters Off an Urbanized Coast of Lake Michigan

    OpenAIRE

    Ryan J Newton; Bootsma, Melinda J.; Morrison, Hilary G; Sogin, Mitchell L.; McLellan, Sandra L.

    2013-01-01

    Urban coasts receive watershed drainage from ecosystems that include highly developed lands with sewer and stormwater infrastructure. In these complex ecosystems, coastal waters are often contaminated with fecal pollution, where multiple delivery mechanisms that often contain multiple fecal sources make it difficult to mitigate the pollution. Here, we exploit bacterial community sequencing of the V6 and V6V4 hypervariable regions of the bacterial 16S rRNA gene to identify bacterial distributi...

  14. Keep Meaning in Conversational Coordination

    Directory of Open Access Journals (Sweden)

    Elena Clare Cuffari

    2014-12-01

    Full Text Available Coordination is a widely employed term across recent quantitative and qualitative approaches to intersubjectivity, particularly approaches that give embodiment and enaction central explanatory roles. With a focus on linguistic and bodily coordination in conversational contexts, I review the operational meaning of coordination in recent empirical research and related theorizing of embodied intersubjectivity. This discussion articulates what must be involved in treating linguistic meaning as dynamic processes of coordination. The coordination approach presents languaging as a set of dynamic self-organizing processes and actions on multiple timescales and across multiple modalities that come about and work in certain domains (those jointly constructed in social, interactive, high-order sense-making. These processes go beyond meaning at the level that is available to first-person experience. I take one crucial consequence of this to be the ubiquitously moral nature of languaging with others. Languaging coordinates experience, among other levels of behavior and event. Ethical effort is called for by the automatic autonomy-influencing forces of languaging as coordination.

  15. Identify Interaction Genes in Genome-Wide Association Studies Using a Model-Based Two-Stage Approach

    OpenAIRE

    Zhang, Zhaogong; Niu, Adan; Sha, Qiuying

    2010-01-01

    In this paper, we propose a two-stage approach based on seventeen biological plausible models to search for two-locus combinations that have significant joint effects on the disease status in genome-wide association (GWA) studies. In the two-stage analyses, we only test two-locus joint effects of SNPs that show modest marginal effects. We use simulation studies to compare the power of our two-stage analysis with a single-marker analysis and a two-stage analysis by using a full model. We find ...

  16. Evaluating Methods for Identifying Cancer in Free-Text Pathology Reports Using Various Machine Learning and Data Preprocessing Approaches.

    Science.gov (United States)

    Kasthurirathne, Suranga Nath; Dixon, Brian E; Grannis, Shaun J

    2015-01-01

    Automated detection methods can address delays and incompleteness in cancer case reporting. Existing automated efforts are largely dependent on complex dictionaries and coded data. Using a gold standard of manually reviewed pathology reports, we evaluated the performance of alternative input formats and decision models on a convenience sample of free-text pathology reports. Results showed that the input format significantly impacted performance, and specific algorithms yielded better results for presicion, recall and accuracy. We conclude that our approach is sufficiently accurate for practical purposes and represents a generalized process.

  17. A current overview of commercially available nucleic acid diagnostics approaches to detect and identify human gastroenteritis pathogens

    Directory of Open Access Journals (Sweden)

    Kate Reddington

    2014-09-01

    The main purpose of this review is to describe a number of recently available multiparametric commercial tests, to support the rapid and accurate clinical diagnosis of human gastroenteritis. These state of the art technologies have the ability to identify a wide range of microorganisms associated with enteric gastroenteritis. Following further technological innovation and more comprehensive clinical validation studies, these NAD tests have the potential to impact on the economic burden of health care systems. These rapid NAD tests can also be used to guide improved patient therapy in a timely manner which will reduce the extent of morbidity and mortality associated with these infections globally.

  18. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

    Directory of Open Access Journals (Sweden)

    Hai-Ming Xu

    Full Text Available The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points. A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s. In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

  19. Global Event-identifier Module: A distributed digital approach to event-of-interest identification logic for physics experiments

    International Nuclear Information System (INIS)

    The demands from current data acquisition systems are to acquire data from a large number of detectors (or signals) while providing a high throughput. This can be achieved by having some preprocessing capability in the data acquisition system so that it can identify the events of interest. Precise selection of events with minimal time for identification and preprocessing is an experimental challenge. To address this challenge, we have developed a ''Global Event-identifier Module'' (GEM) on the CAMAC platform, which can flexibly adapt to the experimental requirements and validate an event with minimal time. GEM is a single width CAMAC module capable of operating in a ''distributed'' data acquisition environment where multiple CAMAC crates (each with one GEM module) can be used to collect synchronized data from all the crates. Event-of-interest decision can be made on signals connected to different crates. Inter-GEM communication is via the ubiquitous ethernet (unshielded twisted pair, CAT5) cable. The event of interest is decided within 32 ns (excluding cable delay). Implementation is accomplished using field programmable gate array which enables greater flexibility for algorithm modifications and updates without hardware changes. GEM supports unified, distributed, and multi-strobe data acquisition, enabling higher throughput, with data collection from a large number of signals by selective reads of events of interest as determined by the experimenter while providing timestamped data of each event.

  20. Identifying and prioritizing factors that influence reapeted patronage of Etka chain-stores customers: a neural network approach

    Directory of Open Access Journals (Sweden)

    Behrouz Jahandideh

    2013-03-01

    Full Text Available Nowadays, chain stores are experiencing a severe competitive environment. In such an environment, a growing number of customers are equipped by high volumes of information and are more risk-taking. As they tend to switch their store based on the higher value that they might receive elsewhere, as customers switching behavior has become so commonplace and has become a challenge for retailers. Thus, factors that influence the willingness of customers to repurchase will play a critical role in the performance and success of chain stores. This paper aimed to identify and prioritize the determinative factors that cause customers repeat patronage in Etka chain stores. Factors were extracted based on a thorough literature review and then these factors were modified using pre-test and interview methods. In this study, questionnaires were used for data collection. Respectively, to identify and prioritize determinative factors, correlation analysis and artificial neural networks were used. Results showed that in order of importance, quality, price loyalty program, number of service counters, store staff, shelf labels, product selection, parking facilities, home delivery, store brand, and store atmosphere are factors that determine customers’ repeat patronage of Etka chain stores. Meanwhile, young, educated and wealthy customers showed lower store repeat patronage. Finally, the paper concludes with suggestions for increasing consumer repeat-patronage of Etka chain-stores and directions for future research.

  1. RUN COORDINATION

    CERN Document Server

    C. Delaere

    2013-01-01

    Since the LHC ceased operations in February, a lot has been going on at Point 5, and Run Coordination continues to monitor closely the advance of maintenance and upgrade activities. In the last months, the Pixel detector was extracted and is now stored in the pixel lab in SX5; the beam pipe has been removed and ME1/1 removal has started. We regained access to the vactank and some work on the RBX of HB has started. Since mid-June, electricity and cooling are back in S1 and S2, allowing us to turn equipment back on, at least during the day. 24/7 shifts are not foreseen in the next weeks, and safety tours are mandatory to keep equipment on overnight, but re-commissioning activities are slowly being resumed. Given the (slight) delays accumulated in LS1, it was decided to merge the two global runs initially foreseen into a single exercise during the week of 4 November 2013. The aim of the global run is to check that we can run (parts of) CMS after several months switched off, with the new VME PCs installed, th...

  2. RUN COORDINATION

    CERN Multimedia

    Christophe Delaere

    2013-01-01

    The focus of Run Coordination during LS1 is to monitor closely the advance of maintenance and upgrade activities, to smooth interactions between subsystems and to ensure that all are ready in time to resume operations in 2015 with a fully calibrated and understood detector. After electricity and cooling were restored to all equipment, at about the time of the last CMS week, recommissioning activities were resumed for all subsystems. On 7 October, DCS shifts began 24/7 to allow subsystems to remain on to facilitate operations. That culminated with the Global Run in November (GriN), which   took place as scheduled during the week of 4 November. The GriN has been the first centrally managed operation since the beginning of LS1, and involved all subdetectors but the Pixel Tracker presently in a lab upstairs. All nights were therefore dedicated to long stable runs with as many subdetectors as possible. Among the many achievements in that week, three items may be highlighted. First, the Strip...

  3. Validation of a Non-Targeted LC-MS Approach for Identifying Ancient Proteins: Method Development on Bone to Improve Artifact Residue Analysis

    Directory of Open Access Journals (Sweden)

    Andrew Barker

    2015-09-01

    Full Text Available Identification of protein residues from prehistoric cooking pottery using mass spectrometry is challenging because proteins are removed from original tissues, are degraded from cooking, may be poorly preserved due to diagenesis, and occur in a palimpsest of exogenous soil proteins. In contrast, bone proteins are abundant and well preserved. This research is part of a larger method-development project for innovation and improvement of liquid chromatography – mass spectrometry analysis of protein residues from cooking pottery; here we validate the potential of our extraction and characterization approach via application to ancient bone proteins. Because of its preservation potential for proteins and given that our approach is destructive, ancient bone identified via skeletal morphology represents an appropriate verification target. Proteins were identified from zooarchaeological turkey (Meleagris gallopavo Linnaeus Phasianidae, rabbit (Lagomorpha, and squirrel (Sciuridae remains excavated from ancient pueblo archaeological sites in southwestern Colorado using a non-targeted LC-MS/MS approach. The data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD002440. Improvement of highly sensitive targeted LC-MS/MS approaches is an avenue for future method development related to the study of protein residues from artifacts such as stone tools and pottery.

  4. Identifying robust clusters and multi-community nodes by combining top-down and bottom-up approaches to clustering

    CERN Document Server

    Gaiteri, Chris; Szymanski, Boleslaw; Kuzmin, Konstantin; Xie, Jierui; Lee, Changkyu; Blanche, Timothy; Neto, Elias Chaibub; Huang, Su-Chun; Grabowski, Thomas; Madhyastha, Tara; Komashko, Vitalina

    2015-01-01

    Biological functions are often realized by groups of interacting molecules or cells. Membership in these groups may overlap when molecules or cells are reused in multiple functions. Traditional clustering methods assign each component to one group. Noisy measurements are common in high-throughput biological datasets. These two limitations reduce our ability to accurately define clusters in biological datasets and to interpret their biological functions. To address these limitations, we designed an algorithm called SpeakEasy, which detects overlapping or non-overlapping communities in biological networks. Input to SpeakEasy can be physical networks, such as molecular interactions, or inferred networks, such as gene coexpression networks. The networks can be directed or undirected, and may contain negative links. SpeakEasy combines traditional bottom-up and top-down approaches to clustering, by creating competition between clusters. Nodes that oscillate between multiple clusters in this competition are classifi...

  5. A COMBINED FUZZY MCDM APPROACH FOR IDENTIFYING THE SUITABLE LANDS FOR URBAN DEVELOPMENT: AN EXAMPLE FROM BANDAR ABBS, IRAN

    Directory of Open Access Journals (Sweden)

    Mohsen Dadras

    2014-01-01

    Full Text Available This study aims at identifying the suitable lands for urban dev elopment in Bandar Abbas city based on its real world use regarding specific crite ria and sub-criteria. The city of Bandar Abbas is considered as the most important commer cial and economic city of Iran. It is also considered as one of the major cities of Iran which has played a pivotal role in the country's development and progress in recen t years especially after the end of Iran-Iraq war owing to its embracing the country's m ain commercial ports. This process has caused the immigration rate into the city to rise significantly over the past 20 years. Thus, the development of the city is meanwhile c onsidered as a high priority. Bandar Abbas city does not have a rich capacity for g rowth and development due to its special geographical situation being located in coastal border. Among the limitations placed in the city's development way, natural limit ations (heights and sea shore in the northern and southern parts of the city and struc tural limitations (military centers in the east and west sides of the city may be referred . Therefore, identifying the suitable lands for urban development within Bandar Abbas city l imits is becoming an essential priority. Therefore, d ifferent quantitative and quali tative criteria have been studied in order to select and identify these lands. The struct ures of qualitative criteria for most parts involve ambiguities and vagueness. This leads us to use Fuzzy logic in this study as a natural method for determining the solutions fo r problems of Multi- criteria decision making (MCDM. In the current research, a com bination of MCDM methods has been presented for analysis. To assignee weights of the criteria Fuzzy AHP (analytic hierarchy process is used for land selection and Fuzzy TOPSIS (method for order priority by similarity to ideal solution is utilized to choose the alternative that is the most appropriate through these criteria weights. The

  6. Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor-specific antigens.

    Science.gov (United States)

    Barnea, Eilon; Beer, Ilan; Patoka, Renana; Ziv, Tamar; Kessler, Ofra; Tzehoval, Esther; Eisenbach, Lea; Zavazava, Nicholas; Admon, Arie

    2002-01-01

    The Human MHC Project aims at comprehensive cataloging of peptides presented within the context of different human leukocyte antigens (HLA) expressed by cells of various tissue origins, both in health and in disease. Of major interest are peptides presented on cancer cells, which include peptides derived from tumor antigens that are of interest for immunotherapy. Here, HLA-restricted tumor-specific antigens were identified by transfecting human breast, ovarian and prostate tumor cell lines with truncated genes of HLA-A2 and HLA-B7. Soluble HLA secreted by these cell lines were purified by affinity chromatography and analyzed by nano-capillary electrospray ionization-tandem mass spectrometry. Typically, a large peptide pool was recovered and sequenced including peptides derived from MAGE-B2 and mucin and other new tumor-derived antigens that may serve as potential candidates for immunotherapy. PMID:11782012

  7. Parenting Coordinators' Practices Recommendations: A Qualitative Study

    OpenAIRE

    Hirsch, Barbara Phyllis

    2016-01-01

    This qualitative study used a phenomenological approach to understand the experiences of seven parenting coordinators in using parenting coordination practices that they have found to be effective and would recommend to other parenting coordinators to achieve the following goals: educating parents, increasing the quality of parenting and co-parenting, managing conflict, and involving children and other family members in the process of parenting coordination. Data were collected with semi-str...

  8. Cladistic approaches to identifying determinants of variability in multifactorial phenotypes and the evolutionary significance of variation in the human genome.

    Science.gov (United States)

    Templeton, A R

    1996-01-01

    Genetic surveys based on detailed restriction site mapping or DNA sequencing allow one to identify many different classes of mutational change at the molecular level and to estimate the evolutionary history of the genetic variation (a haplotype tree). These two sources of information can be combined in a powerful fashion to test hypotheses about the evolutionary significance of genetic variation and to identify mutations that are associated with diseases. Hypotheses about selection on various classes of genetic variation can be tested by examining the distribution patterns of different mutational classes upon the haplotype tree. The power of this procedure can be enhanced if it is coupled with comparative data from other, closely related species. With respect to disease associations, all mutations that affect phenotypic variation in a population occurred at some point in the evolutionary history of the region of the gene containing the mutations. Even if this evolutionary history is estimated from mutations other than those causing phenotypic effects, the phenotypically important mutations are imbedded in this same evolutionary history. Hence, whole branches (clades) of the haplotype tree should display homogeneous phenotypic effects and this fact is utilized to search for phenotypic associations of haplotypes by using nested clades in a haplotype tree. This procedure has more power than alternatives that do not use evolutionary history, and it avoids several statistical and interpretative problems associated with single-marker analyses. All of these methods could be used more extensively if more human genetic surveys concentrated on greater genetic resolution in small DNA regions and included non-human apes.

  9. Multimorbidity patterns in the elderly: a new approach of disease clustering identifies complex interrelations between chronic conditions.

    Directory of Open Access Journals (Sweden)

    Ingmar Schäfer

    Full Text Available OBJECTIVE: Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients' quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. METHODS: Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence ≥ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. RESULTS: Three multimorbidity patterns were found: 1 cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2 anxiety/depression/somatoform disorders and pain [34%; 22%], and 3 neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively and the factors explained a large part of the variance (cumulative percent: 78% and 75%, respectively. The patterns were largely age-dependent and overlapped in a sizeable part of the population. Altogether 50% of female and 48% of male persons were assigned to at least one of the three multimorbidity patterns. CONCLUSION: This study shows that statistically significant co-occurrence of chronic diseases can be subsumed in three prevalent multimorbidity patterns if accounting for the fact that different multimorbidity patterns share some diagnosis groups, influence each other and overlap in a large part of the population. In recognizing the

  10. Interaction of Pb2+, PbMe22+ and PbPh22+ with 3-(phenyl)-2-sulfanylpropenoic acid: a coordinative and toxicological approach.

    Science.gov (United States)

    Félix Camiña, M; Casas, José S; Victoria Castaño, M; Couce, María D; Gato, Angeles; Herbello-Hermelo, Paloma; Sánchez, Agustín; Sordo, José; Dolores Torres, M

    2010-05-01

    We investigated the reaction of Pb(2+), PbMe(2)(2+) and PbPh(2)(2+) with 3-(phenyl)-2-sulfanylpropenoic acid (H(2)pspa) to give the complexes [Pb(pspa)], [PbMe(2)(pspa)], [PbPh(2)(pspa)], [HQ](2)[Pb(pspa)(2)] and [HQ[(2)[PbPh(2)(pspa)(2)] (HQ=diisopropylammonium), which were characterized by IR and NMR ((1)H, (13)C and (207)Pb) spectroscopy and by fast atom bombardment (FAB) spectrometry. The structures of [PbMe(2)(pspa)], [PbPh(2)(pspa)], [PbPh(2)(pspa)(dmso)].dmso and [HQ[(2)[PbPh(2)(pspa)(2)] are interesting examples of unexplored Pb coordination kernels and supramolecular association. Pig renal proximal tubule LLC-PK1 culture cells were used to determine in vitro the effect of the pretreatment with H(2)pspa (alone or combined with vitamin B(6)) and [HQ](2)[Zn(pspa)(2)] on the cytotoxicity of PbMe(2)(2+) and PbPh(2)(2+) by comparing the results with those of meso-2,3-dimercaptosuccinic acid (dmsa). The results show that the cell viability was scarcely affected by these agents. The ability of these reagents to decorporate lead was investigated in vivo by analysing the lead levels in the liver, kidney, brain and blood. In the case of the dimethyl derivative, and under certain protocols, undesirable effects such as an increase in brain and liver lead levels were detected. These increases were not detected when the diphenyl derivative was assayed but in this case a positive effect was not identified either. The blood lead levels also increased in the case of the dimethyl derivative and the activity of delta-ALAD was significantly recovered upon treatment with vitamin B(6) or H(2)pspa; neither the blood lead levels nor the delta-ALAD activity was modified in the case of the diphenyl derivative. PMID:20211491

  11. 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

  12. A comparison of three simple approaches to identify critical areas for runoff and dissolved reactive phosphorus losses

    Science.gov (United States)

    Hahn, C.; Prasuhn, V.; Stamm, C.; Milledge, D. G.; Schulin, R.

    2014-08-01

    Diffuse phosphorus (P) losses are the main cause for eutrophication of surface waters in many regions. Implementing mitigation measures on critical source areas (CSAs) is seen to be the most effective way to reduce P losses. Thus, tools are needed that delineate CSAs on the basis of available data. We compared three models based on different approaches and sets of input data: the rainfall-runoff-phosphorus (RRP) model, the dominant runoff processes (DoRP) model, and the Sensitive Catchment Integrated Modeling Analysis Platform (SCIMAP). The RRP model is a parsimonious dynamic model using the topographic index and a binary soil classification to simulate discharge and P losses. The DoRP model distinguishes eight soil classes based on soil and geological maps. It does not account for topography when calculating runoff. SCIMAP assesses runoff risks solely on the basis of topography using the network index. Compared to surface runoff and soil moisture data available from a catchment in Switzerland, the RRP model and SCIMAP made better predictions than the DoRP model, suggesting that in our study area topography was more important for CSA delineation than soil data. Based on the results, we suggest improvements of SCIMAP to enable average risk predictions and the comparison of risk predictions between catchments.

  13. The FIGS (focused identification of germplasm strategy) approach identifies traits related to drought adaptation in Vicia faba genetic resources.

    Science.gov (United States)

    Khazaei, Hamid; Street, Kenneth; Bari, Abdallah; Mackay, Michael; Stoddard, Frederick L

    2013-01-01

    Efficient methods to explore plant agro-biodiversity for climate change adaptive traits are urgently required. The focused identification of germplasm strategy (FIGS) is one such approach. FIGS works on the premise that germplasm is likely to reflect the selection pressures of the environment in which it developed. Environmental parameters describing plant germplasm collection sites are used as selection criteria to improve the probability of uncovering useful variation. This study was designed to test the effectiveness of FIGS to search a large faba bean (Vicia faba L.) collection for traits related to drought adaptation. Two sets of faba bean accessions were created, one from moisture-limited environments, and the other from wetter sites. The two sets were grown under well watered conditions and leaf morpho-physiological traits related to plant water use were measured. Machine-learning algorithms split the accessions into two groups based on the evaluation data and the groups created by this process were compared to the original climate-based FIGS sets. The sets defined by trait data were in almost perfect agreement to the FIGS sets, demonstrating that ecotypic differentiation driven by moisture availability has occurred within the faba bean genepool. Leaflet and canopy temperature as well as relative water content contributed more than other traits to the discrimination between sets, indicating that their utility as drought-tolerance selection criteria for faba bean germplasm. This study supports the assertion that FIGS could be an effective tool to enhance the discovery of new genes for abiotic stress adaptation.

  14. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

    Science.gov (United States)

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A; Grimsby, Jonna L; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E; Navarro, Pau; Perry, John R B; Rasmussen-Torvik, Laura J; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J; Tanaka, Toshiko; van Duijn, Cornelia M; An, Ping; de Andrade, Mariza; Andrews, Jeanette S; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S; Beilby, John P; Bellis, Claire; Bergman, Richard N; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Borecki, Ingrid B; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S; Clarke, Robert; Collins, Francis S; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo-Riitta; Jhun, Min A; Johnson, Paul C D; Jukema, J Wouter; Jula, Antti; Kao, W H; Kaprio, Jaakko; Kardia, Sharon L R; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J F; Luan, Jian'an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K E; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L; Mooser, Vincent; Morken, Mario A; Miljkovic, Iva; Narisu, Narisu; O'Connell, Jeff; Ong, Ken K; Oostra, Ben A; Palmer, Lyle J; Palotie, Aarno; Pankow, James S; Peden, John F; Pedersen, Nancy L; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P; Province, Michael A; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R; Sijbrands, Eric J G; Siscovick, David S; Smit, Johannes H; Small, Kerrin S; Smith, Nicholas L; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V; Swift, Amy J; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H; Willems, Sara M; Willemsen, Gonneke; Wilson, James F; Witteman, Jacqueline C M; Wright, Alan F; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J; McCarthy, Mark I; Barroso, Ines; Watanabe, Richard M; Florez, Jose C; Dupuis, Josée; Meigs, James B; Langenberg, Claudia

    2012-06-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

  15. swDMR: A Sliding Window Approach to Identify Differentially Methylated Regions Based on Whole Genome Bisulfite Sequencing.

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    Full Text Available DNA methylation is a widespread epigenetic modification that plays an essential role in gene expression through transcriptional regulation and chromatin remodeling. The emergence of whole genome bisulfite sequencing (WGBS represents an important milestone in the detection of DNA methylation. Characterization of differential methylated regions (DMRs is fundamental as well for further functional analysis. In this study, we present swDMR (http://sourceforge.net/projects/swDMR/ for the comprehensive analysis of DMRs from whole genome methylation profiles by a sliding window approach. It is an integrated tool designed for WGBS data, which not only implements accessible statistical methods to perform hypothesis test adapted to two or more samples without replicates, but false discovery rate was also controlled by multiple test correction. Downstream analysis tools were also provided, including cluster, annotation and visualization modules. In summary, based on WGBS data, swDMR can produce abundant information of differential methylated regions. As a convenient and flexible tool, we believe swDMR will bring us closer to unveil the potential functional regions involved in epigenetic regulation.

  16. Quantum Solution of Coordination Problems

    CERN Document Server

    Huberman, B A; Hogg, Tad; Huberman, Bernardo A.

    2003-01-01

    We present a quantum solution to coordination problems that can be implemented with present technologies. It provides an alternative to existing approaches, which rely on explicit communication, prior commitment or trusted third parties. This quantum mechanism applies to a variety of scenarios for which existing approaches are not feasible.

  17. Identifying users of traditional and Internet-based resources for meal ideas: An association rule learning approach.

    Science.gov (United States)

    Doub, Allison E; Small, Meg L; Levin, Aron; LeVangie, Kristie; Brick, Timothy R

    2016-08-01

    Increasing home cooking while decreasing the consumption of food prepared away from home is a commonly recommended weight management strategy, however research on where individuals obtain ideas about meals to cook at home is limited. This study examined the characteristics of individuals who reported using traditional and Internet-based resources for meal ideas. 583 participants who were ≥50% responsible for household meal planning were recruited to approximate the 2014 United States Census distribution on sex, age, race/ethnicity, and household income. Participants reported demographic characteristics, home cooking frequency, and their use of 4 traditional resources for meal ideas (e.g., cookbooks), and 7 Internet-based resources for meal ideas (e.g., Pinterest) in an online survey. Independent samples t-tests compared home cooking frequency by resource use. Association rule learning identified those demographic characteristics that were significantly associated with resource use. Family and friends (71%), food community websites (45%), and cookbooks (41%) were the most common resources reported. Cookbook users reported preparing more meals at home per week (M = 9.65, SD = 5.28) compared to non-cookbook users (M = 8.11, SD = 4.93; t = -3.55, p < 0.001). Resource use was generally higher among parents and varied systematically with demographic characteristics. Findings suggest that home cooking interventions may benefit by modifying resources used by their target population. PMID:27067739

  18. Identifying users of traditional and Internet-based resources for meal ideas: An association rule learning approach.

    Science.gov (United States)

    Doub, Allison E; Small, Meg L; Levin, Aron; LeVangie, Kristie; Brick, Timothy R

    2016-08-01

    Increasing home cooking while decreasing the consumption of food prepared away from home is a commonly recommended weight management strategy, however research on where individuals obtain ideas about meals to cook at home is limited. This study examined the characteristics of individuals who reported using traditional and Internet-based resources for meal ideas. 583 participants who were ≥50% responsible for household meal planning were recruited to approximate the 2014 United States Census distribution on sex, age, race/ethnicity, and household income. Participants reported demographic characteristics, home cooking frequency, and their use of 4 traditional resources for meal ideas (e.g., cookbooks), and 7 Internet-based resources for meal ideas (e.g., Pinterest) in an online survey. Independent samples t-tests compared home cooking frequency by resource use. Association rule learning identified those demographic characteristics that were significantly associated with resource use. Family and friends (71%), food community websites (45%), and cookbooks (41%) were the most common resources reported. Cookbook users reported preparing more meals at home per week (M = 9.65, SD = 5.28) compared to non-cookbook users (M = 8.11, SD = 4.93; t = -3.55, p Resource use was generally higher among parents and varied systematically with demographic characteristics. Findings suggest that home cooking interventions may benefit by modifying resources used by their target population.

  19. Drug Repurposing Approach Identifies Inhibitors of the Prototypic Viral Transcription Factor IE2 that Block Human Cytomegalovirus Replication.

    Science.gov (United States)

    Mercorelli, Beatrice; Luganini, Anna; Nannetti, Giulio; Tabarrini, Oriana; Palù, Giorgio; Gribaudo, Giorgio; Loregian, Arianna

    2016-03-17

    New targets for antiviral strategies are needed against human cytomegalovirus (HCMV), a major human pathogen. A cell-based screen aimed at finding inhibitors of the viral transcription factor Immediate-Early 2 (IE2) was performed in HCMV-infected cells expressing EGFP under the control of an IE2-inducible viral promoter. Screening of a library of bioactive small molecules led to the identification of several compounds able to inhibit EGFP expression and also HCMV replication with potency in the low-micromolar range. Follow-up studies with four selected hits indicated that they all block viral DNA synthesis as well as viral Early and Late gene expression. Furthermore, mechanistic studies confirmed that the compounds specifically act via inhibition of IE2 transactivating activity, thus blocking viral Early gene expression and the progression of virus replication. These results provide proof of concept for identifying small molecules that modulate the activity of a microbial transcription factor to control pathogen replication. PMID:26877023

  20. Identifying patients in target customer segments using a two-stage clustering-classification approach: a hospital-based assessment.

    Science.gov (United States)

    Chen, You-Shyang; Cheng, Ching-Hsue; Lai, Chien-Jung; Hsu, Cheng-Yi; Syu, Han-Jhou

    2012-02-01

    Identifying patients in a Target Customer Segment (TCS) is important to determine the demand for, and to appropriately allocate resources for, health care services. The purpose of this study is to propose a two-stage clustering-classification model through (1) initially integrating the RFM attribute and K-means algorithm for clustering the TCS patients and (2) then integrating the global discretization method and the rough set theory for classifying hospitalized departments and optimizing health care services. To assess the performance of the proposed model, a dataset was used from a representative hospital (termed Hospital-A) that was extracted from a database from an empirical study in Taiwan comprised of 183,947 samples that were characterized by 44 attributes during 2008. The proposed model was compared with three techniques, Decision Tree, Naive Bayes, and Multilayer Perceptron, and the empirical results showed significant promise of its accuracy. The generated knowledge-based rules provide useful information to maximize resource utilization and support the development of a strategy for decision-making in hospitals. From the findings, 75 patients in the TCS, three hospital departments, and specific diagnostic items were discovered in the data for Hospital-A. A potential determinant for gender differences was found, and the age attribute was not significant to the hospital departments. PMID:22177941

  1. A Systems Genetics Approach Identifies Gene Regulatory Networks Associated with Fatty Acid Composition in Brassica rapa Seed.

    Science.gov (United States)

    Basnet, Ram Kumar; Del Carpio, Dunia Pino; Xiao, Dong; Bucher, Johan; Jin, Mina; Boyle, Kerry; Fobert, Pierre; Visser, Richard G F; Maliepaard, Chris; Bonnema, Guusje

    2016-01-01

    Fatty acids in seeds affect seed germination and seedling vigor, and fatty acid composition determines the quality of seed oil. In this study, quantitative trait locus (QTL) mapping of fatty acid and transcript abundance was integrated with gene network analysis to unravel the genetic regulation of seed fatty acid composition in a Brassica rapa doubled haploid population from a cross between a yellow sarson oil type and a black-seeded pak choi. The distribution of major QTLs for fatty acids showed a relationship with the fatty acid types: linkage group A03 for monounsaturated fatty acids, A04 for saturated fatty acids, and A05 for polyunsaturated fatty acids. Using a genetical genomics approach, expression quantitative trait locus (eQTL) hotspots were found at major fatty acid QTLs on linkage groups A03, A04, A05, and A09. An eQTL-guided gene coexpression network of lipid metabolism-related genes showed major hubs at the genes BrPLA2-ALPHA, BrWD-40, a number of seed storage protein genes, and the transcription factor BrMD-2, suggesting essential roles for these genes in lipid metabolism. Three subnetworks were extracted for the economically important and most abundant fatty acids erucic, oleic, linoleic, and linolenic acids. Network analysis, combined with comparison of the genome positions of cis- or trans-eQTLs with fatty acid QTLs, allowed the identification of candidate genes for genetic regulation of these fatty acids. The generated insights in the genetic architecture of fatty acid composition and the underlying complex gene regulatory networks in B. rapa seeds are discussed. PMID:26518343

  2. A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes.

    Directory of Open Access Journals (Sweden)

    Brendan D Galvin

    2014-09-01

    Full Text Available Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT, an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis.

  3. A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes.

    Science.gov (United States)

    Galvin, Brendan D; Li, Zhiru; Villemaine, Estelle; Poole, Catherine B; Chapman, Melissa S; Pollastri, Michael P; Wyatt, Paul G; Carlow, Clotilde K S

    2014-09-01

    Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT), an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM) in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis.

  4. The FIGS (focused identification of germplasm strategy approach identifies traits related to drought adaptation in Vicia faba genetic resources.

    Directory of Open Access Journals (Sweden)

    Hamid Khazaei

    Full Text Available Efficient methods to explore plant agro-biodiversity for climate change adaptive traits are urgently required. The focused identification of germplasm strategy (FIGS is one such approach. FIGS works on the premise that germplasm is likely to reflect the selection pressures of the environment in which it developed. Environmental parameters describing plant germplasm collection sites are used as selection criteria to improve the probability of uncovering useful variation. This study was designed to test the effectiveness of FIGS to search a large faba bean (Vicia faba L. collection for traits related to drought adaptation. Two sets of faba bean accessions were created, one from moisture-limited environments, and the other from wetter sites. The two sets were grown under well watered conditions and leaf morpho-physiological traits related to plant water use were measured. Machine-learning algorithms split the accessions into two groups based on the evaluation data and the groups created by this process were compared to the original climate-based FIGS sets. The sets defined by trait data were in almost perfect agreement to the FIGS sets, demonstrating that ecotypic differentiation driven by moisture availability has occurred within the faba bean genepool. Leaflet and canopy temperature as well as relative water content contributed more than other traits to the discrimination between sets, indicating that their utility as drought-tolerance selection criteria for faba bean germplasm. This study supports the assertion that FIGS could be an effective tool to enhance the discovery of new genes for abiotic stress adaptation.

  5. A transcriptomic approach to identify regulatory genes involved in fruit set of wild-type and parthenocarpic tomato genotypes.

    Science.gov (United States)

    Ruiu, Fabrizio; Picarella, Maurizio Enea; Imanishi, Shunsuke; Mazzucato, Andrea

    2015-10-01

    The tomato parthenocarpic fruit (pat) mutation associates a strong competence for parthenocarpy with homeotic transformation of anthers and aberrancy of ovules. To dissect this complex floral phenotype, genes involved in the pollination-independent fruit set of the pat mutant were investigated by microarray analysis using wild-type and mutant ovaries. Normalized expression data were subjected to one-way ANOVA and 2499 differentially expressed genes (DEGs) displaying a >1.5 log-fold change in at least one of the pairwise comparisons analyzed were detected. DEGs were categorized into 20 clusters and clusters classified into five groups representing transcripts with similar expression dynamics. The "regulatory function" group (685 DEGs) contained putative negative or positive fruit set regulators, "pollination-dependent" (411 DEGs) included genes activated by pollination, "fruit growth-related" (815 DEGs) genes activated at early fruit growth. The last groups listed genes with different or similar expression pattern at all stages in the two genotypes. qRT-PCR validation of 20 DEGs plus other four selected genes assessed the high reliability of microarray expression data; the average correlation coefficient for the 20 DEGs was 0.90. In all the groups were evidenced relevant transcription factors encoding proteins regulating meristem differentiation and floral organ development, genes involved in metabolism, transport and response of hormones, genes involved in cell division and in primary and secondary metabolism. Among pathways related to secondary metabolites emerged genes related to the synthesis of flavonoids, supporting the recent evidence that these compounds are important at the fruit set phase. Selected genes showing a de-regulated expression pattern in pat were studied in other four parthenocarpic genotypes either genetically anonymous or carrying lesions in known gene sequences. This comparative approach offered novel insights for improving the present

  6. Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission

    Science.gov (United States)

    Lau, Colleen L.; Watson, Conall H.; Lowry, John H.; David, Michael C.; Craig, Scott B.; Wynwood, Sarah J.; Kama, Mike; Nilles, Eric J.

    2016-01-01

    Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings. PMID:26820752

  7. Regional Differences of Proteins Expressing in Adipose Depots Isolated from Cows, Steers and Bulls as Identified by a Proteomic Approach.

    Science.gov (United States)

    Cho, Jin Hyoung; Jeong, Jin Young; Lee, Ra Ham; Park, Mi Na; Kim, Seok-Ho; Park, Seon-Min; Shin, Jae-Cheon; Jeon, Young-Joo; Shim, Jung-Hyun; Choi, Nag-Jin; Seo, Kang Seok; Cho, Young Sik; Kim, MinSeok S; Ko, Sungho; Seo, Jae-Min; Lee, Seung-Youp; Chae, Jung-Il; Lee, Hyun-Jeong

    2016-08-01

    Adipose tissue in the loin muscle area of beef cattle as a marbling factor is directly associated with beef quality. To elucidate whether properties of proteins involved in depot specific adipose tissue were sex-dependent, we analyzed protein expression of intramuscular adipose tissue (IMAT) and omental adipose tissue (OMAT) from Hanwoo cows, steers, and bulls of Korean native beef cattle by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis, quantitative polymerase chain reaction (PCR) and western blot analysis. Two different adipose depots (i.e. intramuscular and omental) were collected from cows (n = 7), steers (n = 7), or bulls (n = 7). LC-MS/MS revealed a total of 55 and 35 proteins in IMAT and OMAT, respectively. Of the 55 proteins identified, 44, 40, and 42 proteins were confirmed to be differentially expressed in IMAT of cows, steers, and bulls, respectively. In OMAT of cows, steers, and bulls, 33, 33, and 22 were confirmed to be differentially expressed, respectively. Tropomyosin (TPM) 1, TPM 2, and TPM3 were subjected to verification by quantitative PCR and western blot analysis in IMAT and OMAT of Hanwoo cows, steers, and bulls as key factors closely associated with muscle development. Both mRNA levels and protein levels of TPM1, TPM2, and TPM3 in IMAT were lower in bulls compared to in cows or steers suggesting that they were positively correlated with marbling score and quality grade. Our results may aid the regulation of marbling development and improvement of meat quality grades in beef cattle. PMID:27165017

  8. Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

    Directory of Open Access Journals (Sweden)

    John S Cho

    Full Text Available BACKGROUND: The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood. RESULTS: We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production. CONCLUSIONS: Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

  9. Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission.

    Directory of Open Access Journals (Sweden)

    Colleen L Lau

    2016-01-01

    Full Text Available Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands. Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55, iTaukei ethnicity (OR 3.51, living in villages (OR 1.64, lack of treated water at home (OR 1.52, working outdoors (1.64, living in rural areas (OR 1.43, high poverty rate (OR 1.74, living <100m from a major river (OR 1.41, pigs in the community (OR 1.54, high cattle density in the district (OR 1.04 per head/sqkm, and high maximum rainfall in the wettest month (OR 1.003 per mm. Risk factors and drivers for human leptospirosis infection in Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of

  10. A Machine Learning Approach to Identify Clinical Trials Involving Nanodrugs and Nanodevices from ClinicalTrials.gov

    Science.gov (United States)

    de la Iglesia, Diana; García-Remesal, Miguel; Anguita, Alberto; Muñoz-Mármol, Miguel; Kulikowski, Casimir; Maojo, Víctor

    2014-01-01

    Background Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs—even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. Methods We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. Results and Conclusions The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a

  11. A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov.

    Directory of Open Access Journals (Sweden)

    Diana de la Iglesia

    Full Text Available BACKGROUND: Clinical Trials (CTs are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano, and CTs that do not involve nanotechnology (non-nano. Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. METHODS: We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i extraction and manual annotation of CTs as nano vs. non-nano, ii pre-processing and automatic classification, and iii performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. RESULTS AND CONCLUSIONS: The performance of the best automated classifier closely matches that of experts (AUC over 0.95, suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be

  12. Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission.

    Science.gov (United States)

    Lau, Colleen L; Watson, Conall H; Lowry, John H; David, Michael C; Craig, Scott B; Wynwood, Sarah J; Kama, Mike; Nilles, Eric J

    2016-01-01

    Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living <100m from a major river (OR 1.41), pigs in the community (OR 1.54), high cattle density in the district (OR 1.04 per head/sqkm), and high maximum rainfall in the wettest month (OR 1.003 per mm). Risk factors and drivers for human leptospirosis infection in Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic

  13. Constraining and Tuning the Coordination Geometry of a Lanthanide Ion in Metal-Organic Frameworks: Approach toward a Single-Molecule Magnet.

    Science.gov (United States)

    Liu, Ke; Li, Huanhuan; Zhang, Xuejing; Shi, Wei; Cheng, Peng

    2015-11-01

    It is available to constrain and tune the coordination geometries around lanthanide ions in metal-organic frameworks (MOFs) for the study of single-molecule-magnet (SMM) behavior. A series of Dy(III)-MOFs are synthesized via a solvothermal method by using furan-2,5-dicarboxylic acid (H2FDA) as the ligand. {[Dy2(FDA)3(DMF)2]·1.5DMF}n (1) and [Dy2(FDA)3(DMF)2(CH3OH)]n (2) show similar three-dimensional structures, but the coordination geometries around the dysprosium(III) ions in 1 and 2 exhibit different deviations from ideal square antiprism (D4d symmetry) because of the coordinated solvent molecules. Slow relaxation of the magnetization can be observed for both complexes, indicative of SMM behavior. The effective energy barriers for 1 and 2 can be obtained from alternating-current susceptibility measurements by applying an external 2000 Oe direct-current field. MOF 2 possesses a less distorted D4d coordination sphere and gives a higher effective energy barrier (Ueff) than that of MOF 1. Their diamagnetic Y(III)-diluted samples 1@Y and 2@Y exhibit similar relationships between the geometries and Ueff values, demonstrating that the magnetization relaxation is mainly from the symmetry-related single-ion behavior.

  14. Constraining and Tuning the Coordination Geometry of a Lanthanide Ion in Metal-Organic Frameworks: Approach toward a Single-Molecule Magnet.

    Science.gov (United States)

    Liu, Ke; Li, Huanhuan; Zhang, Xuejing; Shi, Wei; Cheng, Peng

    2015-11-01

    It is available to constrain and tune the coordination geometries around lanthanide ions in metal-organic frameworks (MOFs) for the study of single-molecule-magnet (SMM) behavior. A series of Dy(III)-MOFs are synthesized via a solvothermal method by using furan-2,5-dicarboxylic acid (H2FDA) as the ligand. {[Dy2(FDA)3(DMF)2]·1.5DMF}n (1) and [Dy2(FDA)3(DMF)2(CH3OH)]n (2) show similar three-dimensional structures, but the coordination geometries around the dysprosium(III) ions in 1 and 2 exhibit different deviations from ideal square antiprism (D4d symmetry) because of the coordinated solvent molecules. Slow relaxation of the magnetization can be observed for both complexes, indicative of SMM behavior. The effective energy barriers for 1 and 2 can be obtained from alternating-current susceptibility measurements by applying an external 2000 Oe direct-current field. MOF 2 possesses a less distorted D4d coordination sphere and gives a higher effective energy barrier (Ueff) than that of MOF 1. Their diamagnetic Y(III)-diluted samples 1@Y and 2@Y exhibit similar relationships between the geometries and Ueff values, demonstrating that the magnetization relaxation is mainly from the symmetry-related single-ion behavior. PMID:26465377

  15. Improving Project Manufacturing Coordination

    Directory of Open Access Journals (Sweden)

    Korpivaara Ville

    2014-09-01

    Full Text Available The objective of this research is to develop firms’ project manufacturing coordination. The development will be made by centralizing the manufacturing information flows in one system. To be able to centralize information, a deep user need assessment is required. After user needs have been identified, the existing system will be developed to match these needs. The theoretical background is achieved through exploring the literature of project manufacturing, development project success factors and different frameworks and tools for development project execution. The focus of this research is rather in customer need assessment than in system’s technical expertise. To ensure the deep understanding of customer needs this study is executed by action research method. As a result of this research the information system for project manufacturing coordination was developed to respond revealed needs of the stakeholders. The new system improves the quality of the manufacturing information, eliminates waste in manufacturing coordination processes and offers a better visibility to the project manufacturing. Hence it provides a solid base for the further development of project manufacturing.

  16. Autonomous Control of Distributed Generation and Storage to Coordinate P/Q Sharing in Islanded Microgrids:An Approach beyond Droop Control

    OpenAIRE

    Wu, Dan; Tang, Fen; Guerrero, Josep M.; Vasquez, Juan Carlos

    2014-01-01

    In this paper, a decentralized control for coordinate both active and reactive powers is proposed for islanded microgrids. Compared with the conventional droop control strategies, the proposed control realizes decentralized power distribution among renewable energy sources (RES) and energy storage systems (ESS) according to the local source conditions. Based on bus-signaling method, the ESS is able to limit charging power by decreasing RES power generation automatically. As well, the reactive...

  17. The Influence of Setting on Care Coordination for Childhood Asthma.

    Science.gov (United States)

    Kelly, R Patrick; Stoll, Shelley C; Bryant-Stephens, Tyra; Janevic, Mary R; Lara, Marielena; Ohadike, Yvonne U; Persky, Victoria; Ramos-Valencia, Gilberto; Uyeda, Kimberly; Malveaux, Floyd J

    2015-11-01

    Asthma affects 7.1 million children in the United States, disproportionately burdening African American and Latino children. Barriers to asthma control include insufficient patient education and fragmented care. Care coordination represents a compelling approach to improve quality of care and address disparities in asthma. The sites of The Merck Childhood Asthma Network Care Coordination Programs implemented different models of care coordination to suit specific settings-school district, clinic or health care system, and community-and organizational structures. A variety of qualitative data sources were analyzed to determine the role setting played in the manifestation of care coordination at each site. There were inherent strengths and challenges of implementing care coordination in each of the settings, and each site used unique strategies to deliver their programs. The relationship between the lead implementing unit and entities that provided (1) access to the priority population and (2) clinical services to program participants played a critical role in the structure of the programs. The level of support and infrastructure provided by these entities to the lead implementing unit influenced how participants were identified and how asthma care coordinators were integrated into the clinical care team.

  18. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball and W. Zeuner

    2011-01-01

      Operational experience 2011 CMS is approaching the end of a very successful year of operation. Proton- proton running ended in the late afternoon of 30th October with a stunning 5.73 fb–1 delivered by LHC, of which CMS recorded 5.22 fb–1. During heavy-ion operation, which continues until 7th December, both the accelerator and the CMS detector have also performed very well. Despite the encouraging overall reliability of technical operation, several infrastructure failures which occurred since the last Bulletin are worthy of mention, with one leading for the first time to significant data-loss. On 10th July, a CERN-wide power failure brought down essentially all services including the magnet, due to an MCS setting being left in “manual” after the recent technical stop, but there was no significant damage and the detector was operational before the LHC, despite a slow and tortuous recovery (one of several indications this year that there is room for improve...

  19. TECHNICAL COORDINATION

    CERN Multimedia

    Austin Ball

    2013-01-01

      Since the last report, much visible progress has been made, as the LS1 programme approaches the halfway point. From early October, technical and safety shift-crew have been present around the clock, allowing detectors to stay switched on overnight, ensuring that safety systems are operational and instructions for non-expert shift-crew are clear. LS1 progress Throughout the summer, whilst the solenoid vacuum tank and YB0 surfaces were accessible, an extensive installation programme took place to prepare for Tracker colder operation and the PLT installation, in 2014, the Phase 1 Pixel Tracker installation, in 2016–’17, and the HCAL Phase 1 upgrade completion, ending in LS2. This included pipework for N2 or dry air to flush the Tracker bulkhead region, many sensors to monitor temperature and dew point in the Tracker and its service channels, heating wires outside the Tracker cooling bundles, supports for the new vacuum-jacketed, concentric, CO2 Pixel cooling lines, the PLT cool...

  20. TECHNICAL COORDINATION

    CERN Multimedia

    Austin Ball

    Introduction Underground installation of the initial CMS detector is almost complete. During this CMS week the detector will reach the minimum necessary condition allowing closure for beam. Configuration for pixel, BCM and endcap ECAL installation will then follow, with the installation of one or both endcap ECAL beingdependent on the actual date when beams may be expected through point 5. As we approach the culmination of 9 years of assembly at Cessy, it is appropriate to pay tribute once again to the continuing dedication and flexibility of all the CERN, collaboration and contractor teams working at point 5, including recently our colleagues from AT/VAC. There is every indication that the legacy of their hard work will be a superb scientific instrument. Safety The final burst of assembly activity in the UXC before closing for beam will involve the familiar worksite risks of heavy manipulation, restricted workspaces, multiple activity and work at height, now amplified by the presence of the very fragile be...

  1. A proposed approach to systematically identify and monitor the corporate political activity of the food industry with respect to public health using publicly available information.

    Science.gov (United States)

    Mialon, M; Swinburn, B; Sacks, G

    2015-07-01

    Unhealthy diets represent one of the major risk factors for non-communicable diseases. There is currently a risk that the political influence of the food industry results in public health policies that do not adequately balance public and commercial interests. This paper aims to develop a framework for categorizing the corporate political activity of the food industry with respect to public health and proposes an approach to systematically identify and monitor it. The proposed framework includes six strategies used by the food industry to influence public health policies and outcomes: information and messaging; financial incentive; constituency building; legal; policy substitution; opposition fragmentation and destabilization. The corporate political activity of the food industry could be identified and monitored through publicly available data sourced from the industry itself, governments, the media and other sources. Steps for country-level monitoring include identification of key food industry actors and related sources of information, followed by systematic data collection and analysis of relevant documents, using the proposed framework as a basis for classification of results. The proposed monitoring approach should be pilot tested in different countries as part of efforts to increase the transparency and accountability of the food industry. This approach has the potential to help redress any imbalance of interests and thereby contribute to the prevention and control of non-communicable diseases.

  2. Moving Beyond Drinking to Have a Good Time: a Person-Centered Approach to Identifying Reason Typologies in Legal-Aged College Student Drinkers.

    Science.gov (United States)

    Weybright, Elizabeth H; Cooper, Brittany R; Beckmeyer, Jonathon; Bumpus, Matthew F; Hill, Laura G; Agley, Jon

    2016-08-01

    Alcohol use, reasons for use, and consequences of use continue to be a major concern in college student populations. This is especially true for students of legal drinking age who may experience different reasons for and greater negative consequences of alcohol use than students under 21 years old. Although multiple studies have used person-centered approaches to understand motivations for and ultimately prevent alcohol use, few have identified multiple typologies of reasons for alcohol use. The current study used latent class analysis to identify homogeneous subtypes of reasons for alcohol use and how classification was associated with alcohol-related consequences in college students aged 21 years old and older (N = 2300) from the 2013 Indiana College Substance Use Survey. Four profiles of reasons for alcohol use emerged across males and females: social drinkers, feel good drinkers, relaxed escaping drinkers, and emotion coping drinkers. Although the likelihood of consequences differed across gender, the emotion coping drinkers were more likely to experience all negative consequences, suggesting that it was a high-risk class. In general, this pattern of risk continued with the feel good drinkers and female relaxed escaping drinkers. These results can help optimize college substance use prevention and intervention efforts to (1) identify and understand characteristics of high- and low-risk student drinkers and (2) tailor the content of interventions to those specific profiles resulting in more effective approaches to reducing alcohol use. PMID:27154769

  3. A Novel Approach to Signal Detection of Sensor Array Units Using 5-3-1 Rule Based Matched Filter Algorithm with Intelligent Identifiers

    Directory of Open Access Journals (Sweden)

    Mahmoud Z. Iskandarani

    2010-01-01

    Full Text Available A novel approach to signal detection and identification was developed and tested. The new algorithm was based on provision of tagging a Matched Filter (MF with identifiers to recognize the source signal with and without noise, so that classification can be carried out. The algorithm was applied successfully to chemical Sensor Array Units (SAU. Problem statement: Signals obtained from chemical sensors were sometimes contaminated with noise. Detection of known signals from noisy surroundings was critical in the field of sensors and their applications. Approach: Six chemical sensor array units were tested at different gas concentrations. The testing was carried out under normal conditions and with the presence of noise. The developed algorithm was then applied to detect, identify and classify the results. Results: The 5-3-1 algorithm produced symmetrical arrays with the source signal identifiers at the corners. The symmetry allowed the use of one-third of the produced data for identification, saving processing time and memory storage. Conclusion: The obtained data also proved that gap separation between conducting electrodes to inversely affect device conductance, with different gap widths affected similarly with temperature change per constant deposited film thickness. Also, each device conductance increased in response to increase in applied gas concentration.

  4. Moving Beyond Drinking to Have a Good Time: a Person-Centered Approach to Identifying Reason Typologies in Legal-Aged College Student Drinkers.

    Science.gov (United States)

    Weybright, Elizabeth H; Cooper, Brittany R; Beckmeyer, Jonathon; Bumpus, Matthew F; Hill, Laura G; Agley, Jon

    2016-08-01

    Alcohol use, reasons for use, and consequences of use continue to be a major concern in college student populations. This is especially true for students of legal drinking age who may experience different reasons for and greater negative consequences of alcohol use than students under 21 years old. Although multiple studies have used person-centered approaches to understand motivations for and ultimately prevent alcohol use, few have identified multiple typologies of reasons for alcohol use. The current study used latent class analysis to identify homogeneous subtypes of reasons for alcohol use and how classification was associated with alcohol-related consequences in college students aged 21 years old and older (N = 2300) from the 2013 Indiana College Substance Use Survey. Four profiles of reasons for alcohol use emerged across males and females: social drinkers, feel good drinkers, relaxed escaping drinkers, and emotion coping drinkers. Although the likelihood of consequences differed across gender, the emotion coping drinkers were more likely to experience all negative consequences, suggesting that it was a high-risk class. In general, this pattern of risk continued with the feel good drinkers and female relaxed escaping drinkers. These results can help optimize college substance use prevention and intervention efforts to (1) identify and understand characteristics of high- and low-risk student drinkers and (2) tailor the content of interventions to those specific profiles resulting in more effective approaches to reducing alcohol use.

  5. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball and W. Zeuner

    2012-01-01

      UXC + detectors As explained in detail in the November 2011 bulletin, the bellows unit at −18.5 m from the CMS interaction point was identified as a prime candidate for the regularly occurring pressure spikes which occasionally led to sustained severe background conditions in 2011, affecting dead time and data quality. Similar regions in LHC with vacuum instabilities were observed to be close to bellows, which radiography showed to have distorted RF-fingers — on removal, they proved to have been severely overheated. The plans for the Year-End Technical Stop were adapted to prioritise radiography of the bellows at 16 m to 18 m either end of CMS. Excellent work by the beam pipe, survey and heavy mechanical teams allowed the X-rays to be taken as planned on 20th December, showing that the bellow at −18.5m had an obvious non-conformity. The RF-fingers were found inside the end of the opposing flared pipe instead of outside. In addition, the overlap between fingers and...

  6. Promoting coordination in Norwegian health care

    Directory of Open Access Journals (Sweden)

    Tor I. Romøren

    2011-10-01

    Full Text Available   Introduction: The Norwegian health care system is well organized within its two main sectors - primary health and long term care on the one hand, and hospitals and specialist services on the other. However, the relation between them lacks mediating structures.Policy practice: Enhancing coordination between primary and secondary health care has been central in Norwegian health care policy the last decade. In 2003 a committee was appointed to identify coordination problems and proposed a lot of practical and organisational recommendations. It relied on an approach challenging primary and secondary health care in shared geographical regions to take action. However, these proposals were not implemented. In 2008 a new Minister of Health and Care worked out plans under the key term "Coordination Reform". These reform plans superseded and expanded the previous policy initiatives concerning cooperation, but represented also a shift in focus to a regulative and centralised strategy, including new health legislation, structural reforms and use of economic incentives that are now about to be implemented.Discussion: The article analyses the perspectives and proposals of the previous and the recent reform initiatives in Norway and discusses them in relation to integrated care measures implemented in Denmark and Sweden.

  7. Promoting coordination in Norwegian health care

    Directory of Open Access Journals (Sweden)

    Tor I. Romøren

    2011-10-01

    Full Text Available   Introduction: The Norwegian health care system is well organized within its two main sectors - primary health and long term care on the one hand, and hospitals and specialist services on the other. However, the relation between them lacks mediating structures. Policy practice: Enhancing coordination between primary and secondary health care has been central in Norwegian health care policy the last decade. In 2003 a committee was appointed to identify coordination problems and proposed a lot of practical and organisational recommendations. It relied on an approach challenging primary and secondary health care in shared geographical regions to take action. However, these proposals were not implemented. In 2008 a new Minister of Health and Care worked out plans under the key term "Coordination Reform". These reform plans superseded and expanded the previous policy initiatives concerning cooperation, but represented also a shift in focus to a regulative and centralised strategy, including new health legislation, structural reforms and use of economic incentives that are now about to be implemented. Discussion: The article analyses the perspectives and proposals of the previous and the recent reform initiatives in Norway and discusses them in relation to integrated care measures implemented in Denmark and Sweden.

  8. Equal Opportunities between Men and Women and Gender Mainstreaming under the European Employment Strategy (EES and the Open Method of Coordination (OMC – A New Policy Approach to Combat Gender Discrimination?

    Directory of Open Access Journals (Sweden)

    Beate Braams

    2007-12-01

    Full Text Available The aim of this article is to analyse the development of the concepts of equal opportunities between men and women and gender mainstreaming with regard to a new policy approach taken outside the traditional community method and to raise the question to what extent these policy instruments can be considered as a 'new tool' to combat gender discrimination. The European Employment Strategy (EES and the Open Method of Coordination (OMC are two examples of an instrument outside the community method, which tries to increase the recognition of the gender dimension of the labour market and to improve the initiatives taken in the interrelated field of social inclusion of women by the use of 'soft' policy instruments and voluntarist procedures. The paper illustrates the development of the concept of equal opportunities between men and women and gender mainstreaming under the EES and the OMC; more precisely, the paper seeks to demonstrate that the concepts of equal opportunities between men and women and gender mainstreaming cannot be addressed by reference to harmonisation instruments exclusively, but need, due to the diverse approach towards gender equality on a national level, a decentralised approach as it is offered by the coordination instrument, which should be understood as a complementary tool of integration.

  9. From coordinated care trials to medicare locals: what difference does changing the policy driver from efficiency to quality make for coordinating care?

    Science.gov (United States)

    Gardner, Karen; Yen, Laurann; Banfield, Michelle; Gillespie, James; McRae, Ian; Wells, Robert

    2013-02-01

    The terms coordination and integration refer to a wide range of interventions, from strategies aimed at coordinating clinical care for individuals to organizational and system interventions such as managed care, which contract medical and support services. Ongoing debate about whether financial and organizational integration are needed to achieve clinical integration is evident in policy debates over several decades, from a focus through the 1990s on improving coordination through structural reform and the use of market mechanisms to achieve allocative efficiencies (better overall service mix) to more recent attention on system performance to improve coordination and quality. We examine this shift in Australia and ask how has changing the policy driver affected efforts to achieve coordination? Care planning, fund pooling and purchasing are still important planks in coordination. Evidence suggests that financial strategies can be used to drive improvements for particular patient groups, but these are unlikely to improve outcomes without being linked to clinical strategies that support coordination through multidisciplinary teamwork, IT, disease management guidelines and audit and feedback. Meso level organizational strategies might align the various elements to improve coordination. Changing the policy driver has refocused research and policy over the last two decades from a focus on achieving allocative efficiencies to achieving quality and value for money. Research is yet to develop theoretical approaches that can deal with the implications for assessing effectiveness. Efforts need to identify intervention mechanisms, plausible relationships between these and their measurable outcomes and the components of contexts that support the emergence of intervention attributes.

  10. From coordinated care trials to medicare locals: what difference does changing the policy driver from efficiency to quality make for coordinating care?

    Science.gov (United States)

    Gardner, Karen; Yen, Laurann; Banfield, Michelle; Gillespie, James; McRae, Ian; Wells, Robert

    2013-02-01

    The terms coordination and integration refer to a wide range of interventions, from strategies aimed at coordinating clinical care for individuals to organizational and system interventions such as managed care, which contract medical and support services. Ongoing debate about whether financial and organizational integration are needed to achieve clinical integration is evident in policy debates over several decades, from a focus through the 1990s on improving coordination through structural reform and the use of market mechanisms to achieve allocative efficiencies (better overall service mix) to more recent attention on system performance to improve coordination and quality. We examine this shift in Australia and ask how has changing the policy driver affected efforts to achieve coordination? Care planning, fund pooling and purchasing are still important planks in coordination. Evidence suggests that financial strategies can be used to drive improvements for particular patient groups, but these are unlikely to improve outcomes without being linked to clinical strategies that support coordination through multidisciplinary teamwork, IT, disease management guidelines and audit and feedback. Meso level organizational strategies might align the various elements to improve coordination. Changing the policy driver has refocused research and policy over the last two decades from a focus on achieving allocative efficiencies to achieving quality and value for money. Research is yet to develop theoretical approaches that can deal with the implications for assessing effectiveness. Efforts need to identify intervention mechanisms, plausible relationships between these and their measurable outcomes and the components of contexts that support the emergence of intervention attributes. PMID:23175532

  11. A Socio-Ecological Approach for Identifying and Contextualising Spatial Ecosystem-Based Adaptation Priorities at the Sub-National Level.

    Directory of Open Access Journals (Sweden)

    Amanda Bourne

    Full Text Available Climate change adds an additional layer of complexity to existing sustainable development and biodiversity conservation challenges. The impacts of global climate change are felt locally, and thus local governance structures will increasingly be responsible for preparedness and local responses. Ecosystem-based adaptation (EbA options are gaining prominence as relevant climate change solutions. Local government officials seldom have an appropriate understanding of the role of ecosystem functioning in sustainable development goals, or access to relevant climate information. Thus the use of ecosystems in helping people adapt to climate change is limited partially by the lack of information on where ecosystems have the highest potential to do so. To begin overcoming this barrier, Conservation South Africa in partnership with local government developed a socio-ecological approach for identifying spatial EbA priorities at the sub-national level. Using GIS-based multi-criteria analysis and vegetation distribution models, the authors have spatially integrated relevant ecological and social information at a scale appropriate to inform local level political, administrative, and operational decision makers. This is the first systematic approach of which we are aware that highlights spatial priority areas for EbA implementation. Nodes of socio-ecological vulnerability are identified, and the inclusion of areas that provide ecosystem services and ecological resilience to future climate change is innovative. The purpose of this paper is to present and demonstrate a methodology for combining complex information into user-friendly spatial products for local level decision making on EbA. The authors focus on illustrating the kinds of products that can be generated from combining information in the suggested ways, and do not discuss the nuance of climate models nor present specific technical details of the model outputs here. Two representative case studies from

  12. A Socio-Ecological Approach for Identifying and Contextualising Spatial Ecosystem-Based Adaptation Priorities at the Sub-National Level.

    Science.gov (United States)

    Bourne, Amanda; Holness, Stephen; Holden, Petra; Scorgie, Sarshen; Donatti, Camila I; Midgley, Guy

    2016-01-01

    Climate change adds an additional layer of complexity to existing sustainable development and biodiversity conservation challenges. The impacts of global climate change are felt locally, and thus local governance structures will increasingly be responsible for preparedness and local responses. Ecosystem-based adaptation (EbA) options are gaining prominence as relevant climate change solutions. Local government officials seldom have an appropriate understanding of the role of ecosystem functioning in sustainable development goals, or access to relevant climate information. Thus the use of ecosystems in helping people adapt to climate change is limited partially by the lack of information on where ecosystems have the highest potential to do so. To begin overcoming this barrier, Conservation South Africa in partnership with local government developed a socio-ecological approach for identifying spatial EbA priorities at the sub-national level. Using GIS-based multi-criteria analysis and vegetation distribution models, the authors have spatially integrated relevant ecological and social information at a scale appropriate to inform local level political, administrative, and operational decision makers. This is the first systematic approach of which we are aware that highlights spatial priority areas for EbA implementation. Nodes of socio-ecological vulnerability are identified, and the inclusion of areas that provide ecosystem services and ecological resilience to future climate change is innovative. The purpose of this paper is to present and demonstrate a methodology for combining complex information into user-friendly spatial products for local level decision making on EbA. The authors focus on illustrating the kinds of products that can be generated from combining information in the suggested ways, and do not discuss the nuance of climate models nor present specific technical details of the model outputs here. Two representative case studies from rural South Africa

  13. A Socio-Ecological Approach for Identifying and Contextualising Spatial Ecosystem-Based Adaptation Priorities at the Sub-National Level

    Science.gov (United States)

    Bourne, Amanda; Holness, Stephen; Holden, Petra; Scorgie, Sarshen; Donatti, Camila I.; Midgley, Guy

    2016-01-01

    Climate change adds an additional layer of complexity to existing sustainable development and biodiversity conservation challenges. The impacts of global climate change are felt locally, and thus local governance structures will increasingly be responsible for preparedness and local responses. Ecosystem-based adaptation (EbA) options are gaining prominence as relevant climate change solutions. Local government officials seldom have an appropriate understanding of the role of ecosystem functioning in sustainable development goals, or access to relevant climate information. Thus the use of ecosystems in helping people adapt to climate change is limited partially by the lack of information on where ecosystems have the highest potential to do so. To begin overcoming this barrier, Conservation South Africa in partnership with local government developed a socio-ecological approach for identifying spatial EbA priorities at the sub-national level. Using GIS-based multi-criteria analysis and vegetation distribution models, the authors have spatially integrated relevant ecological and social information at a scale appropriate to inform local level political, administrative, and operational decision makers. This is the first systematic approach of which we are aware that highlights spatial priority areas for EbA implementation. Nodes of socio-ecological vulnerability are identified, and the inclusion of areas that provide ecosystem services and ecological resilience to future climate change is innovative. The purpose of this paper is to present and demonstrate a methodology for combining complex information into user-friendly spatial products for local level decision making on EbA. The authors focus on illustrating the kinds of products that can be generated from combining information in the suggested ways, and do not discuss the nuance of climate models nor present specific technical details of the model outputs here. Two representative case studies from rural South Africa

  14. A systems biology and proteomics-based approach identifies SRC and VEGFA as biomarkers in risk factor mediated coronary heart disease.

    Science.gov (United States)

    V, Alexandar; Nayar, Pradeep G; Murugesan, R; S, Shajahan; Krishnan, Jayalakshmi; Ahmed, Shiek S S J

    2016-07-19

    Coronary heart disease (CHD) is the most common cause of death worldwide. The burden of CHD increases with risk factors such as smoking, hypertension, obesity and diabetes. Several studies have demonstrated the association of these classical risk factors with CHD. However, the mechanisms of these associations remain largely unclear due to the complexity of disease pathophysiology and the lack of an integrative approach that fails to provide a definite understanding of molecular linkage. To overcome these problems, we propose a novel systems biology approach that relates causative genes, interactomes and pathways to elucidate the risk factors mediating the molecular mechanisms and biomarkers for feasible diagnosis. The literature was mined to retrieve the causative genes of each risk factor and CHD to construct protein interactomes. The interactomes were examined to identify 298 common molecular signatures. The common signatures were mapped to the tissue network to synthesize a sub-network consisting of 82 proteins. Further, the dissection of the sub-network provides functional modules representing a diverse range of molecular functions, including the AKT/p13k, MAPK and wnt pathways. Also, the prioritization of functional modules identifies SRC, VEGFA and HIF1A as potential candidate markers. Further, we validate these candidates with the existing markers CRP, NOS3 and VCAM1 in the serum of 63 individuals, 33 with CHD and 30 controls, using ELISA. SRC, VEGFA, H1F1A, CRP and NOS3 were significantly altered in patients compared to controls. These results support the utility of these candidate markers for the diagnosis of CHD. Overall, our molecular observations indicate the influence of risk factors in the pathophysiology of CHD and identify serum markers for diagnosis. PMID:27279347

  15. Molecular dynamics study of the coordination sphere of trivalent lanthanum in a highly concentrated LiCl aqueous solution: A combined classical and ab initio approach

    International Nuclear Information System (INIS)

    The first coordination sphere of trivalent lanthanum in a highly concentrated (14 M) lithium chloride solution is studied with a combination of classical molecular dynamics and density functional theory based first principle molecular dynamics. This method enables us to obtain a solvation shell of La3+ containing 2 chloride ions and 6 water molecules. After refinement using first principle molecular dynamics, the resulting cation-water and cation-anion distances are in very good agreement with experiment. The 2 Cl- and the 6 water molecules arrange in a square anti-prism around La3+. Exchange of water molecules was also observed in the first-principle simulation, with an intermediate structure comprising 7 water molecules stable for 2.5 ps. Finally, evaluation of dipole moments using maximally localized Wannier functions shows a substantial polarization of the chloride anions and the water molecules in the first solvation shell of trivalent lanthanum. (authors)

  16. The “Retrofitting” Approach to Adapting Evidence-Based Interventions: A Case Study of Pediatric Asthma Care Coordination, United States, 2010–2014

    Science.gov (United States)

    Stoll, Shelley C.; Lara, Marielena; Ramos-Valencia, Gilberto; Stephens, Tyra Bryant; Persky, Victoria; Uyeda, Kimberly; Lesch, Julie Kennedy; Malveaux, Floyd J.

    2016-01-01

    Adaptation of evidence-based interventions upon implementation into new practice settings is universal, yet poorly understood. During a cross-site evaluation of the implementation of a proven intervention for pediatric asthma care coordination into 4 resource-challenged settings, we conducted in-depth interviews with site representatives, who reported how and why they modified intervention components. Interview notes were coded for themes. We focused on a single theme from a respondent who described the adaptation process as “backing” the intervention into ongoing services; we found evidence of a similar process at other sites. We labeled this process “retrofitting” to signify adaptation that consists of altering existing services to align with intervention components, rather than modifying the intervention to fit a new setting. Advantages of retrofitting may include allowing organizations to keep what works, capitalizing on existing support for program activities, elevating the role of local knowledge, and potentially promoting the sustainability of effective innovations. PMID:27560722

  17. The "Retrofitting" Approach to Adapting Evidence-Based Interventions: A Case Study of Pediatric Asthma Care Coordination, United States, 2010-2014.

    Science.gov (United States)

    Janevic, Mary R; Stoll, Shelley C; Lara, Marielena; Ramos-Valencia, Gilberto; Bryant-Stephens, Tyra; Persky, Victoria; Uyeda, Kimberly; Lesch, Julie Kennedy; Malveaux, Floyd J

    2016-01-01

    Adaptation of evidence-based interventions upon implementation into new practice settings is universal, yet poorly understood. During a cross-site evaluation of the implementation of a proven intervention for pediatric asthma care coordination into 4 resource-challenged settings, we conducted in-depth interviews with site representatives, who reported how and why they modified intervention components. Interview notes were coded for themes. We focused on a single theme from a respondent who described the adaptation process as "backing" the intervention into ongoing services; we found evidence of a similar process at other sites. We labeled this process "retrofitting" to signify adaptation that consists of altering existing services to align with intervention components, rather than modifying the intervention to fit a new setting. Advantages of retrofitting may include allowing organizations to keep what works, capitalizing on existing support for program activities, elevating the role of local knowledge, and potentially promoting the sustainability of effective innovations. PMID:27560722

  18. Identifying potential candidates for donor–acceptor copolymers on a series of 4H-1,2,6-thiadiazines: An electrochemical approach

    International Nuclear Information System (INIS)

    Highlights: • Electrochemistry on thiadiazine-based compounds. • Energy level approximation. • Low-bandgap copolymer electron accepting building blocks. • Design rules for “push–pull” copolymerization approaches using thiadiazines. -- Abstract: A series of synthesized small organic molecules based on the 4H-1,2,6-thiadiazine moiety are studied using electrochemistry, to probe their potential as comonomer building blocks for solar-absorbing polymers for organic solar cells. This is the first instance of an electrochemical report for this family of heterocycles. Structure–physical property relationships are identified that can guide future synthetic efforts. Parameters that can influence the properties of the final copolymer such as the choice of electron donor comonomer and the energy level of the fullerene adduct acceptor are factored-in and discussed and the thiadiazines that can meet the requirements are singled-out

  19. Robust full-length hepatitis C virus genotype 2a and 2b infectious cultures using mutations identified by a systematic approach applicable to patient strains

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M;

    2012-01-01

    Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases worldwide, but treatment options are limited. Basic HCV research required for vaccine and drug development has been hampered by inability to culture patient isolates, and to date only the JFH1 (genotype 2a) recombinant...... in vitro. Through a systematic approach of culturing J6 with minimal JFH1 sequences, we identified three mutations in NS3, NS4A, and NS5B that permitted full-length J6 propagation and adaptation with infectivity titers comparable to JFH1-based systems. The most efficient recombinant, J6cc, had six adaptive...... mutations and did not accumulate additional changes following viral passage. We demonstrated that HCV NS3/NS4A protease-, NS5A- and NS5B polymerase-directed drugs respectively inhibited full-length J6 infection dose dependently. Importantly, the three J6-derived mutations enabled culture adaptation...

  20. A comprehensive approach to identify reliable reference gene candidates to investigate the link between alcoholism and endocrinology in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Faten A Taki

    Full Text Available Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2 is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR. The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO, ovariectomized rats in the absence (OVX or presence of E2 (OVXE2. These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.

  1. A comprehensive approach to identify reliable reference gene candidates to investigate the link between alcoholism and endocrinology in Sprague-Dawley rats.

    Science.gov (United States)

    Taki, Faten A; Abdel-Rahman, Abdel A; Zhang, Baohong

    2014-01-01

    Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2) is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR). The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs) as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder) was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO), ovariectomized rats in the absence (OVX) or presence of E2 (OVXE2). These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.

  2. Linking gene regulation and the exo-metabolome: A comparative transcriptomics approach to identify genes that impact on the production of volatile aroma compounds in yeast

    Directory of Open Access Journals (Sweden)

    Bauer Florian F

    2008-11-01

    Full Text Available Abstract Background 'Omics' tools provide novel opportunities for system-wide analysis of complex cellular functions. Secondary metabolism is an example of a complex network of biochemical pathways, which, although well mapped from a biochemical point of view, is not well understood with regards to its physiological roles and genetic and biochemical regulation. Many of the metabolites produced by this network such as higher alcohols and esters are significant aroma impact compounds in fermentation products, and different yeast strains are known to produce highly divergent aroma profiles. Here, we investigated whether we can predict the impact of specific genes of known or unknown function on this metabolic network by combining whole transcriptome and partial exo-metabolome analysis. Results For this purpose, the gene expression levels of five different industrial wine yeast strains that produce divergent aroma profiles were established at three different time points of alcoholic fermentation in synthetic wine must. A matrix of gene expression data was generated and integrated with the concentrations of volatile aroma compounds measured at the same time points. This relatively unbiased approach to the study of volatile aroma compounds enabled us to identify candidate genes for aroma profile modification. Five of these genes, namely YMR210W, BAT1, AAD10, AAD14 and ACS1 were selected for overexpression in commercial wine yeast, VIN13. Analysis of the data show a statistically significant correlation between the changes in the exo-metabome of the overexpressing strains and the changes that were predicted based on the unbiased alignment of transcriptomic and exo-metabolomic data. Conclusion The data suggest that a comparative transcriptomics and metabolomics approach can be used to identify the metabolic impacts of the expression of individual genes in complex systems, and the amenability of transcriptomic data to direct applications of

  3. Multi-Agent Systems for Transportation Planning and Coordination

    NARCIS (Netherlands)

    J.M. Moonen (Hans)

    2009-01-01

    textabstractMany transportation problems are in fact coordination problems: problems that require communication, coordination and negotiation to be optimally solved. However, most software systems targeted at transportation have never approached it this way, and have instead concentrated on centrali

  4. Identifying strategies for mitigating the global warming impact of the EU-25 economy using a multi-objective input–output approach

    International Nuclear Information System (INIS)

    Global warming mitigation has recently become a priority worldwide. A large body of literature dealing with energy related problems has focused on reducing greenhouse gases emissions at an engineering scale. In contrast, the minimization of climate change at a wider macroeconomic level has so far received much less attention. We investigate here how to mitigate global warming by performing changes in an economy. To this end, we make use of a systematic tool that combines three methods: linear programming, environmentally extended input output models, and life cycle assessment principles. The problem of identifying key economic sectors that contribute significantly to global warming is posed in mathematical terms as a bi-criteria linear program that seeks to optimize simultaneously the total economic output and the total life cycle CO2 emissions. We have applied this approach to the European Union economy, finding that significant reductions in global warming potential can be attained by regulating specific economic sectors. Our tool is intended to aid policy makers in the design of more effective public policies for achieving the environmental and economic targets sought. - Highlights: • We minimize climate change by performing small changes in the consumption habits. • We propose a tool that combines multiobjective optimization and macroeconomic models. • Identifying key sectors allows improving the environmental performance significantly with little impact to the economy. • Significant reductions in global warming potential are attained by regulating sectors. • Our tool aids policy makers in the design of effective sustainability policies

  5. Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network Cohort

    Directory of Open Access Journals (Sweden)

    Kaveri S. Parker

    2016-05-01

    Full Text Available Interstitial cystitis/bladder pain syndrome (IC/BPS is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S, a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS.

  6. Network Coordinator Report

    Science.gov (United States)

    Himwich, Ed; Strand, Richard

    2013-01-01

    This report includes an assessment of the network performance in terms of lost observing time for the 2012 calendar year. Overall, the observing time loss was about 12.3%, which is in-line with previous years. A table of relative incidence of problems with various subsystems is presented. The most significant identified causes of loss were electronics rack problems (accounting for about 21.8% of losses), antenna reliability (18.1%), RFI (11.8%), and receiver problems (11.7%). About 14.2% of the losses occurred for unknown reasons. New antennas are under development in the USA, Germany, and Spain. There are plans for new telescopes in Norway and Sweden. Other activities of the Network Coordinator are summarized.

  7. Combinatorial and Computational Approaches to Identify Interactions of Macrophage Colony-stimulating Factor (M-CSF) and Its Receptor c-FMS.

    Science.gov (United States)

    Rosenfeld, Lior; Shirian, Jason; Zur, Yuval; Levaot, Noam; Shifman, Julia M; Papo, Niv

    2015-10-23

    The molecular interactions between macrophage colony-stimulating factor (M-CSF) and the tyrosine kinase receptor c-FMS play a key role in the immune response, bone metabolism, and the development of some cancers. Because no x-ray structure is available for the human M-CSF · c-FMS complex, the binding epitope for this complex is largely unknown. Our goal was to identify the residues that are essential for binding of the human M-CSF to c-FMS. For this purpose, we used a yeast surface display (YSD) approach. We expressed a combinatorial library of monomeric M-CSF (M-CSFM) single mutants and screened this library to isolate variants with reduced affinity for c-FMS using FACS. Sequencing yielded a number of single M-CSFM variants with mutations both in the direct binding interface and distant from the binding site. In addition, we used computational modeling to map the identified mutations onto the M-CSFM structure and to classify the mutations into three groups as follows: those that significantly decrease protein stability; those that destroy favorable intermolecular interactions; and those that decrease affinity through allosteric effects. To validate the YSD and computational data, M-CSFM and three variants were produced as soluble proteins; their affinity and structure were analyzed; and very good correlations with both YSD data and computational predictions were obtained. By identifying the M-CSFM residues critical for M-CSF · c-FMS interactions, we have laid down the basis for a deeper understanding of the M-CSF · c-FMS signaling mechanism and for the development of target-specific therapeutic agents with the ability to sterically occlude the M-CSF·c-FMS binding interface. PMID:26359491

  8. 浅析分级诊疗体系建设国际经验%International approaches to coordinated care delivery systems

    Institute of Scientific and Technical Information of China (English)

    肖月; 赵琨; 史黎炜; 丁干

    2015-01-01

    阐述了不同国家对分级诊疗体系建设的情况及经验,介绍了不同卫生筹资体制国家所采用的诊疗体系,以及多数国家确定各级各类医疗卫生服务机构的职责和服务范围情况以及确保患者有序流动的措施情况,最后归纳各国分级诊疗做法的四点经验并提出对我国分级诊疗工作的启示。%This paper summarized practices and experiences of other countries in coordinated care delivery system building,and described the care delivery systems used in various healthcare fundraising patterns.It is found that most countries have defined duties and service coverage of healthcare institutions at all the levels and measures to ensure rational patient flow.In the end,the paper concluded found experiences of these countries and inspirations for China.

  9. A Coordination Chemistry Approach for Lithium-Ion Batteries: The Coexistence of Metal and Ligand Redox Activities in a One-Dimensional Metal-Organic Material.

    Science.gov (United States)

    Li, Gaihua; Yang, Hao; Li, Fengcai; Cheng, Fangyi; Shi, Wei; Chen, Jun; Cheng, Peng

    2016-05-16

    We demonstrate herein the use of a one-dimensional metal-organic material as a new type of electrode material for lithium-ion batteries (LIBs) in place of the classic porous three-dimensional materials, which are subject to the size of the channel for lithium-ion diffusion and blocking of the windows of the framework by organic solvents during the charging and discharging processes. Introducing a one-dimensional coordination compound can keep organic active substances insoluble in the electrolyte during the charging and discharging processes, providing a facile and general new system for further studies. The results show that both the aromatic ligand and the metal center can participate in lithium storage simultaneously, illustrating a new energy storage mechanism that has been well-characterized by X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and cyclic voltammetry. In addition, the fact that the one-dimensional chains are linked by weak hydrogen bonds rather than strong π-π stacking interactions or covalent bonds is beneficial for the release of capacity entirely without the negative effect of burying the active sites.

  10. Coupled 3D Time-Dependent Wave-Packet Approach in Hyperspherical Coordinates: The D(+)+H2 Reaction on the Triple-Sheeted DMBE Potential Energy Surface.

    Science.gov (United States)

    Ghosh, Sandip; Sahoo, Tapas; Adhikari, Satrajit; Sharma, Rahul; Varandas, António J C

    2015-12-17

    We implement a coupled three-dimensional (3D) time-dependent wave packet formalism for the 4D reactive scattering problem in hyperspherical coordinates on the accurate double many body expansion (DMBE) potential energy surface (PES) for the ground and first two singlet states (1(1)A', 2(1)A', and 3(1)A') to account for nonadiabatic processes in the D(+) + H2 reaction for both zero and nonzero values of the total angular momentum (J). As the long-range interactions in D(+) + H2 contribute significantly due to nonadiabatic effects, the convergence profiles of reaction probabilities for the reactive noncharge transfer (RNCT), nonreactive charge transfer (NRCT), and reactive charge transfer (RCT) processes are shown for different collisional energies with respect to the helicity (K) and total angular momentum (J) quantum numbers. The total and state-to-state cross sections are presented as a function of the collision energy for the initial rovibrational state v = 0, j = 0 of the diatom, and the calculated cross sections compared with other theoretical and experimental results. PMID:26436891

  11. Processing Coordination Ambiguity

    Science.gov (United States)

    Engelhardt, Paul E.; Ferreira, Fernanda

    2010-01-01

    We examined temporarily ambiguous coordination structures such as "put the butter in the bowl and the pan on the towel." Minimal Attachment predicts that the ambiguous noun phrase "the pan" will be interpreted as a noun-phrase coordination structure because it is syntactically simpler than clausal coordination. Constraint-based theories assume…

  12. Control coordination abilities in shock combat sports

    Directory of Open Access Journals (Sweden)

    Natalya Boychenko

    2014-12-01

    Full Text Available Purpose: optimize the process control level of coordination abilities in martial arts. Material and Methods: analysis and compilation of scientific and methodological literature, interviews with coaches of drum martial arts, video analysis techniques, teacher observations. Results: identified specific types of coordination abilities in shock combat sports. Pod branny and offered specific and nonspecific tests to monitor the level of species athletes coordination abilities. Conclusion: it is determined that in order to achieve victory in the fight martial artists to navigate the space to be able to assess and manage dynamic and spatio-temporal parameters of movements, maintain balance, have a high coordination of movements. The proposed tests to monitor species coordination abilities athletes allow an objective assessment of not only the overall level of coordination, and the level of specific types of manifestations of this ability.

  13. Impairments of social motor coordination in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Manuel Varlet

    Full Text Available It has been demonstrated that motor coordination of interacting people plays a crucial role in the success of social exchanges. Abnormal movements have been reported during interpersonal interactions of patients suffering from schizophrenia and a motor coordination breakdown could explain this social interaction deficit, which is one of the main and earliest features of the illness. Using the dynamical systems framework, the goal of the current study was (i to investigate whether social motor coordination is impaired in schizophrenia and (ii to determine the underlying perceptual or cognitive processes that may be affected. We examined intentional and unintentional social motor coordination in participants oscillating hand-held pendulums from the wrist. The control group consisted of twenty healthy participant pairs while the experimental group consisted of twenty participant pairs that included one participant suffering from schizophrenia. The results showed that unintentional social motor coordination was preserved while intentional social motor coordination was impaired. In intentional coordination, the schizophrenia group displayed coordination patterns that had lower stability and in which the patient never led the coordination. A coupled oscillator model suggests that the schizophrenia group coordination pattern was due to a decrease in the amount of available information together with a delay in information transmission. Our study thus identified relational motor signatures of schizophrenia and opens new perspectives for detecting the illness and improving social interactions of patients.

  14. Toward a General Yet Effective Computational Approach for Diffusive Problems: Variable Diffusion Tensor and DVR Solution of the Smoluchowski Equation along a General One-Dimensional Coordinate.

    Science.gov (United States)

    Piserchia, Andrea; Barone, Vincenzo

    2016-08-01

    A generalization to arbitrary large amplitude motions of a recent approach to the evaluation of diffusion tensors [ J. Comput. Chem. , 2009 , 30 , 2 - 13 ] is presented and implemented in a widely available package for electronic structure computations. A fully black-box tool is obtained, which, starting from the generation of geometric structures along different kinds of paths, proceeds toward the evaluation of an effective diffusion tensor and to the solution of one-dimensional Smoluchowski equations by a robust numerical approach rooted in the discrete variable representation (DVR). Application to a number of case studies shows that the results issuing from our approach are identical to those delivered by previous software (in particular DiTe) for rigid scans along a dihedral angle, but can be improved by employing relaxed scans (i.e., constrained geometry optimizations) or even more general large amplitude paths. The theoretical and numerical background is robust and general enough to allow quite straightforward extensions in several directions (e.g., inclusion of reactive paths, solution of Fokker-Planck or stochastic Liouville equations, multidimensional problems, free-energy rather than electronic-energy driven processes). PMID:27403666

  15. Identifying the genetic variation of gene expression using gene sets: application of novel gene Set eQTL approach to PharmGKB and KEGG.

    Directory of Open Access Journals (Sweden)

    Ryan Abo

    Full Text Available Genetic variation underlying the regulation of mRNA gene expression in humans may provide key insights into the molecular mechanisms of human traits and complex diseases. Current statistical methods to map genetic variation associated with mRNA gene expression have typically applied standard linkage and/or association methods; however, when genome-wide SNP and mRNA expression data are available performing all pair wise comparisons is computationally burdensome and may not provide optimal power to detect associations. Consideration of different approaches to account for the high dimensionality and multiple testing issues may provide increased efficiency and statistical power. Here we present a novel approach to model and test the association between genetic variation and mRNA gene expression levels in the context of gene sets (GSs and pathways, referred to as gene set - expression quantitative trait loci analysis (GS-eQTL. The method uses GSs to initially group SNPs and mRNA expression, followed by the application of principal components analysis (PCA to collapse the variation and reduce the dimensionality within the GSs. We applied GS-eQTL to assess the association between SNP and mRNA expression level data collected from a cell-based model system using PharmGKB and KEGG defined GSs. We observed a large number of significant GS-eQTL associations, in which the most significant associations arose between genetic variation and mRNA expression from the same GS. However, a number of associations involving genetic variation and mRNA expression from different GSs were also identified. Our proposed GS-eQTL method effectively addresses the multiple testing limitations in eQTL studies and provides biological context for SNP-expression associations.

  16. A Qualitative Approach of Identifying Major Cost Influencing Factors in Palm Oil Mills and the Relations towards Production Cost of Crude Palm Oil

    Directory of Open Access Journals (Sweden)

    Elaine L.Y. Man

    2011-01-01

    Full Text Available Problem statement: The oil palm industry, which heavily depends on the world market, is an export oriented industry. Worlds palm oil consumption was growing over the years. In addition, Indonesia and Malaysia dominated the oil palm industry. The oil palm industry in Malaysia is very competitive and become one of the major economic sectors contributing to the total revenue of the country. In year 2009, there was a total of 22.40 million tons of oil palm products including palm oil, palm kernel oil, palm kernel cake, oleo-chemicals and finished products, equivalent to RM 49.59 billion of export revenue. However, cost of production for Crude Palm Oil (CPO varies in a big gap. Therefore, it is essential to identify the major cost influencing factors in the production of CPO. Approach: The study system started with collection of Fresh Fruits Bunches (FFB from oil palm plantation to the production of CPO at palm oil mills. Two palm oil mills of different production capacity were chosen for this study. Statistical analysis was done to identify the major cost influencing factors of production cost for CPO. Results: The production cost of CPO for small scale palm oil mills preferably lied between RM 45 to RM 50 per metric tons while large scale palm oil mills lied below RM 45 per metric tons. Conclusion: Palm oil mills with higher production capacity were efficient in producing CPO than lower production capacity palm oil mills. Thus, the production cost of CPO was lower compared to that of small scale palm oil mills.

  17. Utility of machine learning approaches to identify behavioral markers for substance use disorders: Impulsivity dimensions as predictors of current cocaine dependence

    Directory of Open Access Journals (Sweden)

    Woo-Young eAhn

    2016-03-01

    Full Text Available Background: Identifying objective and accurate markers of cocaine dependence (CD can innovate its prevention and treatment. Existing evidence suggests that CD is characterized by a wide range of cognitive deficits, most notably by increased impulsivity. Impulsivity is multidimensional and it is unclear which of its various dimensions would have the highest predictive utility for CD. The machine learning approach is highly promising for discovering predictive markers of disease. Here we used machine learning to identify multivariate predictive patterns of impulsivity phenotypes that can accurately classify individuals with CD. Methods: Current cocaine-dependent users (N=31 and healthy controls (N=23 completed the self-report Barratt Impulsiveness Scale (BIS-11 and five neurocognitive tasks indexing different dimensions of impulsivity: (1 Immediate Memory Task (IMT; (2 Stop-Signal Task (SST; (3 Delay-Discounting Task (DDT; (4 Iowa Gambling Task (IGT; and (5 Probabilistic Reversal Learning (PRL task. We applied a machine learning algorithm to all impulsivity measures. Results: Machine learning accurately classified individuals with CD and predictions were generalizable to new samples (area under the curve of the ROC curve was 0.912 in the test set. CD membership was predicted by higher scores on motor and non-planning trait impulsivity, poor response inhibition and discriminability on the IMT, higher delay discounting on the DDT, and poor decision-making on the IGT.Conclusions: Our results suggest that multivariate behavioral impulsivity phenotypes can predict CD with high degree of accuracy, which can potentially be used to assess individuals’ vulnerability to CD in clinical settings.

  18. A novel chemical footprinting approach identifies critical lysine residues involved in the binding of receptor-associated protein to cluster II of LDL receptor-related protein.

    Science.gov (United States)

    Bloem, Esther; Ebberink, Eduard H T M; van den Biggelaar, Maartje; van der Zwaan, Carmen; Mertens, Koen; Meijer, Alexander B

    2015-05-15

    Tandem mass tags (TMTs) were utilized in a novel chemical footprinting approach to identify lysine residues that mediate the interaction of receptor-associated protein (RAP) with cluster II of LDL (low-density lipoprotein) receptor (LDLR)-related protein (LRP). The isolated RAP D3 domain was modified with TMT-126 and the D3 domain-cluster II complex with TMT-127. Nano-LC-MS analysis revealed reduced modification with TMT-127 of peptides including Lys(256), Lys(270) and Lys(305)-Lys(306) suggesting that these residues contribute to cluster II binding. This agrees with previous findings that Lys(256) and Lys(270) are critical for binding cluster II sub-domains [Fisher, Beglova and Blacklow (2006) Mol. Cell 22, 277-283]. Cluster II-binding studies utilizing D3 domain variants K(256)A, K(305)A and K(306)A now showed that Lys(306) contributes to cluster II binding as well. For full-length RAP, we observed that peptides including Lys(60), Lys(191), Lys(256), Lys(270) and Lys(305)-Lys(306) exhibited reduced modification with TMT in the RAP-cluster II complex. Notably, Lys(60) has previously been implicated to mediate D1 domain interaction with cluster II. Our results suggest that also Lys(191) of the D2 domain contributes to cluster II binding. Binding studies employing the RAP variants K(191)A, K(256)A, K(305)A and K(306)A, however, revealed a modest reduction in cluster II binding for the K(256)A variant only. This suggests that the other lysine residues can compensate for the absence of a single lysine residue for effective complex assembly. Collectively, novel insight has been obtained into the contribution of lysine residues of RAP to cluster II binding. In addition, we propose that TMTs can be utilized to identify lysine residues critical for protein complex formation. PMID:25728577

  19. RapidArc combined with the active breathing coordinator provides an effective and accurate approach for the radiotherapy of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gong, G.Z.; Yin, Y.; Xing, L.G.; Guo, Y.J.; Liu, T.; Chen, J.; Lu, J.; Ma, C.; Sun, T.; Bai, T.; Zhang, G.; Wang, R. [Shandong Academy of Medical Sciences, Jinan (China). Dept. of Radiation Oncology

    2012-03-15

    The goal of this research was to investigate the feasibility of volumetric modulated arc therapy, RapidArc (RA), in association with the active breathing coordinator (ABC) for the treatment of hepatocellular carcinoma (HCC) with radiotherapy. A total of 12 patients with HCC, after receiving transcatheter arterial chemoembolization (TACE) treatment, underwent three-dimensional computer tomography (3D-CT) scanning associated with ABC using end inspiration hold (EIH), end expiration hold (EEH), and free breathing (FB) techniques. The three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and RA plans (three 135 arcs) were designed on different CT images, respectively. The liver volume, gross tumor volume (GTV), and planning target volume (PTV) of the three breath status and the dosimetric differences of the different plans were compared. There were no significant differences in the volumes of live and GTV between the three breathing techniques (p > 0.05); the PTV in FB was greater than in the EEH and EIH (p < 0.05). The overall conformality index (CI) and homogeneity index (HI) for RA (CI 0.92, HI 0.90) were better than IMRT (CI 0.90, HI 0.89) and 3D-CRT (CI 0.70, HI 0.84) for the three breathing techniques (p< 0.05). The RA and IMRT significantly reduced the mean dose, V{sub 20}, V{sub 30}, and V{sub 40} of normal liver compared to 3D-CRT, while the V{sub 5} and V{sub 10} in RA were higher than in IMRT. The mean values in mean dose, V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40} of the normal liver were reduced from 13.12 Gy, 46%, 24%, 13%, and 8% in RA{sub FB} to 10.23 Gy, 35%, 16%, 8%, and 5% in RA{sub EEH} and 9.23 Gy, 32%, 16%, 8%, and 5% in RA{sub EIH}, respectively. In addition, the treatment time of RA was equal to 3D-CRT, which was significantly shorter than IMRT. RA in conjunction with ABC for the treatment of HCC with radiotherapy can achieve better dose delivery and ensure the accuracy of the target volume, which spares

  20. Movement coordination during conversation.

    Science.gov (United States)

    Latif, Nida; Barbosa, Adriano V; Vatikiotis-Bateson, Eric; Vatiokiotis-Bateson, Eric; Castelhano, Monica S; Munhall, K G

    2014-01-01

    Behavioral coordination and synchrony contribute to a common biological mechanism that maintains communication, cooperation and bonding within many social species, such as primates and birds. Similarly, human language and social systems may also be attuned to coordination to facilitate communication and the formation of relationships. Gross similarities in movement patterns and convergence in the acoustic properties of speech have already been demonstrated between interacting individuals. In the present studies, we investigated how coordinated movements contribute to observers' perception of affiliation (friends vs. strangers) between two conversing individuals. We used novel computational methods to quantify motor coordination and demonstrated that individuals familiar with each other coordinated their movements more frequently. Observers used coordination to judge affiliation between conversing pairs but only when the perceptual stimuli were restricted to head and face regions. These results suggest that observed movement coordination in humans might contribute to perceptual decisions based on availability of information to perceivers. PMID:25119189

  1. Movement coordination during conversation.

    Directory of Open Access Journals (Sweden)

    Nida Latif

    Full Text Available Behavioral coordination and synchrony contribute to a common biological mechanism that maintains communication, cooperation and bonding within many social species, such as primates and birds. Similarly, human language and social systems may also be attuned to coordination to facilitate communication and the formation of relationships. Gross similarities in movement patterns and convergence in the acoustic properties of speech have already been demonstrated between interacting individuals. In the present studies, we investigated how coordinated movements contribute to observers' perception of affiliation (friends vs. strangers between two conversing individuals. We used novel computational methods to quantify motor coordination and demonstrated that individuals familiar with each other coordinated their movements more frequently. Observers used coordination to judge affiliation between conversing pairs but only when the perceptual stimuli were restricted to head and face regions. These results suggest that observed movement coordination in humans might contribute to perceptual decisions based on availability of information to perceivers.

  2. Adventures in Coordinate Space

    Science.gov (United States)

    Chambers, J. E.

    2003-08-01

    A variety of coordinate systems have been used to study the N-body problem for cases involving a dominant central mass. These include the traditional Keplerian orbital elements and the canonical Delaunay variables, which both incorporate conserved quantities of the two-body problem. Recently, Cartesian coordinate systems have returned to favour with the rise of mixed-variable symplectic integrators, since these coordinates prove to be more efficient than using orbital elements. Three sets of canonical Cartesian coordinates are well known, each with its own advantages and disadvantages. Inertial coordinates (which include barycentric coordinates as a special case) are the simplest and easiest to implement. However, they suffer from the disadvantage that the motion of the central body must be calculated explicitly, leading to relatively large errors in general. Jacobi coordinates overcome this problem by replacing the coordinates and momenta of the central body with those of the system as a whole, so that momentum is conserved exactly. This leads to substantial improvements in accuracy, but has the disadvantage that every object is treated differently, and interactions between each pair of bodies are now expressed in a complicated manner involving the coordinates of many bodies. Canonical heliocentric coordinates (also known as democratic heliocentric coordinates) treat all bodies equally, and conserve the centre of mass motion, but at the cost of introducing momentum cross terms into the kinetic energy. This complicates the development of higher order symplectic integrators and symplectic correctors, as well as the development of methods used to resolve close encounters with the central body. Here I will re-examine the set of possible canonical Cartesian coordinate systems to determine if it is possible to (a) conserve the centre of mass motion, (b) treat all bodies equally, and (c) eliminate the momentum cross terms. I will demonstrate that this is indeed possible

  3. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

    Directory of Open Access Journals (Sweden)

    Clive J Hoggart

    2014-07-01

    Full Text Available The phenotypic effect of some single nucleotide polymorphisms (SNPs depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI. Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios. Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene and the paternal rs3091869-T allele (located near the SLC2A10 gene increased BMI equally (beta = 0.11 (SD, P<0.0027 compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01. Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

  4. Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Directory of Open Access Journals (Sweden)

    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  5. A combined remote sensing and modeling based approach to identify sustainable pathways for urban and peri-urban agriculture in China

    Science.gov (United States)

    Wattenbach, M.; Delgado, J. M.; Roessner, S.; Bochow, M.; Güntner, A.; Kropp, J.; Cantu Ros, A. G.; Hattermann, F.; Kolbe, T.; Sodoudi, S.; Cubasch, U. Ulrich; Zeitz, J.; Ross, L.; Böckel, K.; Fang, C.; Bo, L.; Pan, G.

    2012-04-01

    As the world's biggest economy, China is becoming the biggest consumer of resources globally. Given this trend, the over-proportional fast increase in urbanization presents China with fundamental problems. Among the most urgent ones is the increasing loss of agricultural land as urbanization takes place in the most productive regions along the coast. The latter is being responsible for a shift in agriculture production towards climatically less favorable areas. At the same time, the loss of green areas in and around growing cities is increasing the effect of the urban heat island. The perception of the potential risks related to this phenomenon, in the context of climate change, has led the Shanghai city administration to increase its urban-greening efforts, expanding the per capita area of green from 1m2 in 1990 to 12.5m2 in 2008. In this context, this paper aims at identifying the influence of urban and peri-urban agriculture (UPA) on the sustainability of the urban regions of Shanghai and Nanjing. In particular, it focuses on the effects of UPA on the greenhouse gas (GHG) emissions, soil nutrients and water balances, local climate and the structure and functions of the urbanized areas. We propose an interdisciplinary framework combining remote sensing, model simulations and GHG field observations and targeted at identifying "win-win" strategies for sustainable planning pathways showing high potentials for UPA. The framework is based on spatial scenario modeling, automatic classification of urban structure types and on a prototype of a high-quality spatial database consisting of a 3D city model. Dynamic boundary conditions for climate and urban development are provided by state of the art models. These approaches meet the needs of stakeholders and planners in China. A special emphasis is put on interdependencies between small holder farming in the urban and peri-urban zone and climate change adaptation and mitigation strategies focusing on improved management of

  6. Coordinating Interactions: The Event Coordination Notation

    DEFF Research Database (Denmark)

    Kindler, Ekkart

    on a much more technical level. The Event Coordination Notation (ECNO) allows modelling the behaviour of an application on a high level of abstraction that is closer to the application’s domain than to the software realizing it. Still, these models contain all necessary details for actually executing....... The global behaviour of the application results from different elements jointly engaging in such events, which is called an interaction. Which events are supposed to be jointly executed and which elements need to join in is defined by so-called coordination diagrams of the ECNO. Together, the models...

  7. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  8. Enhanced time overcurrent coordination

    Energy Technology Data Exchange (ETDEWEB)

    Enriquez, Arturo Conde; Martinez, Ernesto Vazquez [Universidad Autonoma de Nuevo Leon, Facultad de Ingenieria Mecanica y Electrica, Apdo. Postal 114-F, Ciudad Universitaria, CP 66450 San Nicolas de los Garza, Nuevo Leon (Mexico)

    2006-04-15

    In this paper, we recommend a new coordination system for time overcurrent relays. The purpose of the coordination process is to find a time element function that allows it to operate using a constant back-up time delay, for any fault current. In this article, we describe the implementation and coordination results of time overcurrent relays, fuses and reclosers. Experiments were carried out in a laboratory test situation using signals of a power electrical system physics simulator. (author)

  9. Salmonella enterica Infections in the United States and Assessment of Coefficients of Variation: A Novel Approach to Identify Epidemiologic Characteristics of Individual Serotypes, 1996-2011.

    Directory of Open Access Journals (Sweden)

    Amy L Boore

    Full Text Available Despite control efforts, salmonellosis continues to cause an estimated 1.2 million infections in the United States (US annually. We describe the incidence of salmonellosis in the US and introduce a novel approach to examine the epidemiologic similarities and differences of individual serotypes.Cases of salmonellosis in humans reported to the laboratory-based National Salmonella Surveillance System during 1996-2011 from US states were included. Coefficients of variation were used to describe distribution of incidence rates of common Salmonella serotypes by geographic region, age group and sex of patient, and month of sample isolation.During 1996-2011, more than 600,000 Salmonella isolates from humans were reported, with an average annual incidence of 13.1 cases/100,000 persons. The annual reported rate of Salmonella infections did not decrease during the study period. The top five most commonly reported serotypes, Typhimurium, Enteritidis, Newport, Heidelberg, and Javiana, accounted for 62% of fully serotyped isolates. Coefficients of variation showed the most geographically concentrated serotypes were often clustered in Gulf Coast states and were also more frequently found to be increasing in incidence. Serotypes clustered in particular months, age groups, and sex were also identified and described.Although overall incidence rates of Salmonella did not change over time, trends and epidemiological factors differed remarkably by serotype. A better understanding of Salmonella, facilitated by this comprehensive description of overall trends and unique characteristics of individual serotypes, will assist in responding to this disease and in planning and implementing prevention activities.

  10. Multiomics approach to identify novel biomarkers for dilated cardiomyopathy: Proteome and transcriptome analyses of 4C30 dilated cardiomyopathy mouse model.

    Science.gov (United States)

    Nishigori, Mitsuhiro; Yagi, Hiroaki; Mochiduki, Akikazu; Minamino, Naoto

    2016-11-01

    Dilated cardiomyopathy (DCM) is an intractable disease, without any radical treatment option other than cardiac transplantation. Additionally, biomarkers to determine progressive staging are not yet available. Irrespective of the diversity of causative gene mutations, the phenotype of DCM is rather common. Therefore, it is plausible to determine DCM staging in terms of variations in protein and mRNA levels. In this study, we performed proteome and transcriptome analysis of the left ventricle of 4C30 DCM model mice showing mild and severe phenotypes at 12 and 24 weeks (wk) after birth, respectively. Proteomic analyses results showed 109 proteins that increased and 133 others that decreased among 1874 detected proteins. We selected biomarker candidates by confirming consistent alterations in protein levels at 12 and 24 wk, and mRNA levels at 12 wk, and narrowed these down based on the requirement that they should be detectable in blood. Finally, we selected six biomarker candidates based on sustained or augmented alteration at 24 wk and confirmed their definite alterations in the left ventricle by quantitative polymerase chain reaction, western blot analysis, and multiple reaction monitoring (MRM). To assess the validity of this strategy, we measured plasma concentrations of the six candidates by MRM method and identified two proteins (FTL1 and GRP78) that demonstrated significant elevation in the 4C30 mice plasma. Taken together, a multiomics strategy comparing tissue expression levels of proteins and mRNAs between diseased and control groups, with appropriate confirmation, is a promising approach for the discovery of new biomarkers. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 491-502, 2016. PMID:26799926

  11. DEVELOPMENTAL COORDINATION DISORDER IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Saeideh MIRAFKHAMI

    2010-03-01

    Full Text Available ObjectiveIn this article, a motor skill disorder called developmental coordination disorder (DCD, that is usually first diagnosed during childhood, is explained and discussed. In the year 1987, DCD was formally recognized as a distinct disorder in children by the American Psychiatric Association (APA. DCD is a generalized term for the children who have some degrees of impairment in the development of motor coordination and therefore have difficulties with physical skills which significantly interfere with their academic achievements and /or performing everyday activities. As they develop, other age-related tasks are also below average. Because these impairment & conditions are often associated with emotional distress, they can seriously interfere with the person's everyday life and social relationships. Reviews indicate that most of the training rocedures have only a limited effect on the development of general coordination, and that they have no effect at all on academic progress.This includes approaches based on assumed underlying deficiencies such as sensory integration deficits and kinesthetic functioning deficits, as well as the more traditional perceptual - motor training. One new approach is Cognitive Orientation to daily Occupational Performance (CO-OP, based on problem - solving strategies and guided discovery of the child and task specific strategies. The aim of this article was to inform, promote and disseminate more information about some difficulties in applying the diagnostic criteria for DCD. Also, a brief review of the researches on the intervention methods is presented.

  12. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose;

    2012-01-01

    In a coordination game with Pareto-ranked equilibria, we study whether a sunspot can lead to either coordination on an inferior equilibrium (mis-coordination) or to out-of equilibrium behavior (dis-coordination). While much of the literature searches for mechanisms to attain coordination on the e......In a coordination game with Pareto-ranked equilibria, we study whether a sunspot can lead to either coordination on an inferior equilibrium (mis-coordination) or to out-of equilibrium behavior (dis-coordination). While much of the literature searches for mechanisms to attain coordination...

  13. Social Postural Coordination

    Science.gov (United States)

    Varlet, Manuel; Marin, Ludovic; Lagarde, Julien; Bardy, Benoit G.

    2011-01-01

    The goal of the current study was to investigate whether a visual coupling between two people can produce spontaneous interpersonal postural coordination and change their intrapersonal postural coordination involved in the control of stance. We examined the front-to-back head displacements of participants and the angular motion of their hip and…

  14. Coordinate measuring machines

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceability...

  15. PATONGO: Patterns and Tools for Non-Profit Organizations—a pattern-based approach for helping volunteers to identify and share good practice

    Science.gov (United States)

    Schümmer, Till; Haake, Jörg M.

    2010-04-01

    Identification and sharing of good practice is an essential ingredient for collaborative voluntary action in non-profit organizations. While current approaches for sharing good practice focus on adopting and describing good practice individually, they fail to address collaborative detection, description, and appropriation of good practice in organizations. We propose a pattern-based approach, which facilitates collaborative creation, improvement, and sharing of good practice via Web 2.0 concepts. First experiences with the approach are presented including a field experiment where the approach was implemented in the Evangelic Church of Germany.

  16. Integrated Approach (Geophysics and Remote Sensing) to identify Water-bearing Dyke Swarms and Fractured Basement in the Sinai Peninsula, Egypt

    Science.gov (United States)

    Mohamed, L.; Sultan, M.; Ahmed, M. E.; Sauck, W.; Abouelmagd, A. A.; Chouinard, K.

    2012-12-01

    An integrated approach utilizing Very Low Frequency (VLF) and magnetic field surveying and temporal remote sensing data including: (1) Advanced Space Borne Thermal Emission and Reflection (ASTER) data, (2) European Remote Sensing (ERS-1 and ERS-2) radar imagery, and (3) Tropical Rainfall Measuring Mission (TRMM) was used to delineate water-bearing sub-vertical shear zones within the basement complex of the Sinai Peninsula. The following steps were undertaken: (1) the shear zones and dyke swarms within the basement complex were delineated using false color ASTER band and band ratio images; (2) the spatial and temporal precipitation events over the basement complex were then identified from TRMM data, and (3) finally, observations extracted from temporal radar and thermal ASTER bands were used to identify the water-bearing shear zones and dyke swarms. A fracture or dyke was deemed to be water bearing if: (1) it witnessed a large increase in its reflectivity and emissivity compared to its surroundings following a precipitation event, and maintained such differences for periods ranging from days to months. Field observations and VLF investigations were then applied to test the validity of our satellite-based methodologies for locating targeted aquifer types and for refining the satellite-based selections. The VLF detects conductive water-saturated subvertical breccia zones in bedrock. Thirty two VLF transects were collected in September of 2011 and July of 2012 along with 10 magnetic profiles at the same VLF locations. Both VLF and magnetic transects were acquired along a traverse perpendicular to the dike orientations with station separations ranging from 10 to 25 m. The VLF receiver (T-VLF) measures the distortion of the normally horizontal electromagnetic flux lines by local electrical conductors. At each VLF station, and for each frequency used, the following were measured: the tilt of the electromagnetic field, from the horizontal (given in percentage), the

  17. Adaptive coordination in surgical teams: an interview study

    OpenAIRE

    Bogdanovic, Jasmina; Perry, Juliana; Guggenheim, Merlin; Manser, Tanja

    2015-01-01

    Background Effective teamwork has been recognised as a major contributor to safe patient care in surgery. Previous research has highlighted the importance of adaptive coordination for effective performance in acute care settings. Expanding this line of research this study explores the coordination behaviours and adaptive coordination strategies employed by surgical teams and identifies relevant situational characteristics influencing those coordination processes. Method We conducted a qualita...

  18. Psiscan: a computational approach to identify H/ACA-like and AGA-like non-coding RNA in trypanosomatid genomes

    Directory of Open Access Journals (Sweden)

    Ziporen Yaara

    2008-11-01

    Full Text Available Abstract Background Detection of non coding RNA (ncRNA molecules is a major bioinformatics challenge. This challenge is particularly difficult when attempting to detect H/ACA molecules which are involved in converting uridine to pseudouridine on rRNA in trypanosomes, because these organisms have unique H/ACA molecules (termed H/ACA-like that lack several of the features that characterize H/ACA molecules in most other organisms. Results We present here a computational tool called Psiscan, which was designed to detect H/ACA-like molecules in trypanosomes. We started by analyzing known H/ACA-like molecules and characterized their crucial elements both computationally and experimentally. Next, we set up constraints based on this analysis and additional phylogenic and functional data to rapidly scan three trypanosome genomes (T. brucei, T. cruzi and L. major for sequences that observe these constraints and are conserved among the species. In the next step, we used minimal energy calculation to select the molecules that are predicted to fold into a lowest energy structure that is consistent with the constraints. In the final computational step, we used a Support Vector Machine that was trained on known H/ACA-like molecules as positive examples and on negative examples of molecules that were identified by the computational analyses but were shown experimentally not to be H/ACA-like molecules. The leading candidate molecules predicted by the SVM model were then subjected to experimental validation. Conclusion The experimental validation showed 11 molecules to be expressed (4 out of 25 in the intermediate stage and 7 out of 19 in the final validation after the machine learning stage. Five of these 11 molecules were further shown to be bona fide H/ACA-like molecules. As snoRNA in trypanosomes are organized in clusters, the new H/ACA-like molecules could be used as starting points to manually search for additional molecules in their neighbourhood. All

  19. Sensory Motor Coordination in Robonaut

    Science.gov (United States)

    Peters, Richard Alan, II

    2003-01-01

    As a participant of the year 2000 NASA Summer Faculty Fellowship Program, I worked with the engineers of the Dexterous Robotics Laboratory at NASA Johnson Space Center on the Robonaut project. The Robonaut is an articulated torso with two dexterous arms, left and right five-fingered hands, and a head with cameras mounted on an articulated neck. This advanced space robot, now driven only teleoperatively using VR gloves, sensors and helmets, is to be upgraded to a thinking system that can find, interact with and assist humans autonomously, allowing the Crew to work with Robonaut as a (junior) member of their team. Thus, the work performed this summer was toward the goal of enabling Robonaut to operate autonomously as an intelligent assistant to astronauts. Our underlying hypothesis is that a robot can develop intelligence if it learns a set of basic behaviors (i.e., reflexes - actions tightly coupled to sensing) and through experience learns how to sequence these to solve problems or to accomplish higher-level tasks. We describe our approach to the automatic acquisition of basic behaviors as learning sensory-motor coordination (SMC). Although research in the ontogenesis of animals development from the time of conception) supports the approach of learning SMC as the foundation for intelligent, autonomous behavior, we do not know whether it will prove viable for the development of autonomy in robots. The first step in testing the hypothesis is to determine if SMC can be learned by the robot. To do this, we have taken advantage of Robonaut's teleoperated control system. When a person teleoperates Robonaut, the person's own SMC causes the robot to act purposefully. If the sensory signals that the robot detects during teleoperation are recorded over several repetitions of the same task, it should be possible through signal analysis to identify the sensory-motor couplings that accompany purposeful motion. In this report, reasons for suspecting SMC as the basis for

  20. Trust and team coordination in critical situations

    OpenAIRE

    Adrian H. Pitariu

    2008-01-01

    In this paper I explore the process of team coordination. I propose a model by which team coordination emerges as a function of team mental models and team trust. Furthermore, I introduce a hierarchical approach to team mental models, and propose a framework that provides a better understanding of team processes and opens new avenues of research in the area of team cognition. I conclude with implications for future research and practice.