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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. Identifiability of linear systems in physical coordinates

    Science.gov (United States)

    Su, Tzu-Jeng; Juang, Jer-Nan

    1992-01-01

    Identifiability of linear, time-invariant systems in physical coordinates is discussed. It is shown that identification of the system matrix in physical coordinates can be accomplished by determining a transformation matrix that relates the physical locations of actuators and sensors to the test-data-derived input and output matrices. For systems with symmetric matrices, the solution of a constrained optimization problem is used to characterize all the possible solutions of the transformation matrix. Conditions for the existence of a unique transformation matrix are established easily from the explicit form of the solutions. For systems with limited inputs and outputs, the question about which part of the system can be uniquely identified is also answered. A simple mass-spring system is used to verify the conclusions of this study.

  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

    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.

  5. 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.

  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. Coordinate transformation approach to social interactions

    Directory of Open Access Journals (Sweden)

    Steve W C Chang

    2013-08-01

    Full Text Available A coordinate transformation framework for understanding how neurons compute sensorimotor behaviors has generated significant advances towards our understanding of basic brain function. This influential scaffold focuses on neuronal encoding of spatial information represented in different coordinate systems (e.g., eye-centered, hand-centered and how multiple brain regions partake in transforming these signals in order to ultimately generate a motor output. A powerful analogy can be drawn from the coordinate transformation framework to better elucidate how the nervous system computes cognitive variables for social behavior. Of particular relevance is how the brain represents information with respect to oneself and other individuals, such as in reward outcome assignment during social exchanges, in order to influence social decisions. In this article, I outline how the coordinate transformation framework can help guide our understanding of neural computations resulting in social interactions. Implications for numerous psychiatric disorders with impaired representations of self and others are also discussed.

  8. 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

  9. 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....

  10. 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.

  11. Identifying play characteristics of pre-school children with developmental coordination disorder via parental questionnaires.

    Science.gov (United States)

    Rosenblum, Sara; Waissman, Pola; Diamond, Gary W

    2016-11-18

    Motor coordination deficits that characterize children with Developmental Coordination Disorder (DCD) affect their quality of participation. The aim of the current study was to identify play characteristics of young children with DCD, compared to those of children with typical development in three dimensions: activity and participation, environmental factors and children's impairments.

  12. 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.

  13. 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.

  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. A trichordal temporal approach to digital coordination: the sociomaterial mangling of the CERN grid

    CERN Document Server

    Venters, Will; Barrett, Michael

    2014-01-01

    This paper develops a sociomaterial perspective on dig ital coordination. It extends Pickering’s mangle of practice by using a trichordal approach to temporal em ergence. We provide new understanding as to how the nonhuman and human agencies involved in coordination are embedded in the past, present, and future. We draw on an in-depth field study conducted between 2006 and 2010 of the development, introduction, and use of a computing grid infrastructure by the CERN partic le physics community. Three coordination tensions are identified at different temporal dimensions, namely obtaining adequate transparency in the present, modeling a future infrastructure, and the historical disciplining of social and material inertias. We propose and develop the concept of digital coordination, and contribut e a trichordal temporal approach to understanding the development and use of digital infrastructure as being or ientated to the past and future while emerging in the present.

  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 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. How Do Teachers Coordinate Their Work? A Framing Approach

    Science.gov (United States)

    Dumay, Xavier

    2014-01-01

    Since the 1970s, schools have been characterized as loosely coupled systems, meaning that the teachers' work is weakly coordinated at the local level. Nonetheless, few studies have focused on the local variations of coordination modes, their sources and their nature. In this article, the process of local coordination of the teachers' work is…

  7. An alternative approach to field-aligned coordinates for plasma turbulence simulations

    CERN Document Server

    Ottaviani, M A

    2010-01-01

    Turbulence simulation codes can exploit the flute-like nature of plasma turbulence to reduce the effective number of degrees of freedom necessary to represent fluctuations. This can be achieved by employing magnetic coordinates of which one is aligned along the magnetic field. This work presents an approach in which the position along the field lines is identified by the toroidal angle, rather than the most commonly used poloidal angle. It will be shown that this approach has several advantages. Among these, periodicity in both angles is retained. This property allows moving to an equivalent representation in Fourier space with a reduced number of toroidal components. It will be shown how this duality can be exploited to transform conventional codes that use a spectral representation on the magnetic surface into codes with a field-aligned coordinate. It is also shown that the new approach can be generalised to get rid of magnetic coordinates in the poloidal plane altogether, for a large class of models. Tests...

  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. Coordinates of a New Romanian Regional Policy - Identifying the Development Poles. A Case Study

    Directory of Open Access Journals (Sweden)

    Adriana DAVIDESCU

    2014-01-01

    Full Text Available The sustainable regional development is a crucial topic at the level of the EU nowadays. Therefore, the regional policies of the member states should be constructed in such a fashion, that they comply with the general European framework and maximize the potential of reaching the European goals. Following the general trend, Romania finds itself today in a complex project of rethinking its regional approach. The approach proposed in this paper will try, using statistical methods and aggregate data available in the Tempo database, to identify those counties that have the necessary characteristics in order to be taken in consideration when choosing the core county of each new region.

  11. 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.

  12. A Coordinated Approach to Raising the Socio-Economic Status of Latinos in California.

    Science.gov (United States)

    Lopez, Elias, Ed.; Puddefoot, Ginny, Ed.; Gandara, Patricia, Ed.

    This report presents a collection of papers that focuses on a coordinated approach to raising the socioeconomic status of Hispanic Americans living in California. After presenting "The Need for a Coordinated Approach," the papers are: "Preschool Access" (Theresa Garcia, Sandra Gutierrez, and Giovanna Stark); "K-12…

  13. Covert Flow Graph Approach to Identifying Covert Channels

    OpenAIRE

    XiangMei Song; ShiGuang Ju

    2011-01-01

    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 ...

  14. Identifying coordinative structure using principal component analysis based on coherence derived from linear systems analysis.

    Science.gov (United States)

    Wang, Xinguang; O'Dwyer, Nicholas; Halaki, Mark; Smith, Richard

    2013-01-01

    Principal component analysis is a powerful and popular technique for capturing redundancy in muscle activity and kinematic patterns. A primary limitation of the correlations or covariances between signals on which this analysis is based is that they do not account for dynamic relations between signals, yet such relations-such as that between neural drive and muscle tension-are widespread in the sensorimotor system. Low correlations may thus be obtained and signals may appear independent despite a dynamic linear relation between them. To address this limitation, linear systems analysis can be used to calculate the matrix of overall coherences between signals, which measures the strength of the relation between signals taking dynamic relations into account. Using ankle, knee, and hip sagittal-plane angles from 6 healthy subjects during ~50% of total variance in the data set, while with overall coherence matrices the first component accounted for > 95% of total variance. The results demonstrate that the dimensionality of the coordinative structure can be overestimated using conventional correlation, whereas a more parsimonious structure is identified with overall coherence.

  15. 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.

  16. Spectral transform approaches of 3D coordinates for object classification

    OpenAIRE

    Semenov, N.; Leontiev, A.

    2008-01-01

    This article describes one of the methods to process the data for subsequent classification spectral processing of the three dimensional data. This processing allows, using minimal amount of computation, to transfer the object's coordinates to the starting point, as well as to turn the object around any axis and normalize its size.

  17. 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.

  18. A predictive approach to identify genes differentially expressed

    Science.gov (United States)

    Saraiva, Erlandson F.; Louzada, Francisco; Milan, Luís A.; Meira, Silvana; Cobre, Juliana

    2012-10-01

    The main objective of gene expression data analysis is to identify genes that present significant changes in expression levels between a treatment and a control biological condition. In this paper, we propose a Bayesian approach to identify genes differentially expressed calculating credibility intervals from predictive densities which are constructed using sampled mean treatment effect from all genes in study excluding the treatment effect of genes previously identified with statistical evidence for difference. We compare our Bayesian approach with the standard ones based on the use of the t-test and modified t-tests via a simulation study, using small sample sizes which are common in gene expression data analysis. Results obtained indicate that the proposed approach performs better than standard ones, especially for cases with mean differences and increases in treatment variance in relation to control variance. We also apply the methodologies to a publicly available data set on Escherichia coli bacteria.

  19. 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.

  20. 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.

  1. A Novel Distributed Secondary Coordination Control Approach for Islanded Microgrids

    DEFF Research Database (Denmark)

    Lu, Xiaoqing; Yu, Xinghuo; Lai, Jingang

    2017-01-01

    This paper develops a new distributed secondary cooperative control scheme to coordinate distributed generators (DGs) in islanded microgrids (MGs). A finite time frequency regulation strategy containing a consensus-based distributed active power regulator is presented, which can not only guarantee...... controllers are equipped with bounded control inputs to suppress the transient overshoot, and they are implemented through sparse communication networks. The effectiveness of the control in case of load variation, plug-and-play capability, communication topology change, link failure, time delays and data drop...

  2. Collective coordinates, shape transitions and shape coexistence a microscopic approach

    CERN Document Server

    Nakatsukasa, T; Nakatsukasa, Takashi; Walet, Niels R.

    1998-01-01

    We investigate a description of shape-mixing and shape-transitions using collective coordinates. To that end we apply a theory of adiabatic large-amplitude motion to a simplified nuclear shell-model, where the approximate results can be contrasted with exact diagonalisations. We find excellent agreement for different regimes, and contrast the results with those from a more standard calculation using a quadrupole constraint. We show that the method employed in this work selects diabatic (crossing) potential energy curves where these are appropriate, and discuss the implications for a microscopic study of shape coexistence.

  3. 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.

  4. A Computer Vision Approach to Identify Einstein Rings and Arcs

    Science.gov (United States)

    Lee, Chien-Hsiu

    2017-03-01

    Einstein rings are rare gems of strong lensing phenomena; the ring images can be used to probe the underlying lens gravitational potential at every position angles, tightly constraining the lens mass profile. In addition, the magnified images also enable us to probe high-z galaxies with enhanced resolution and signal-to-noise ratios. However, only a handful of Einstein rings have been reported, either from serendipitous discoveries or or visual inspections of hundred thousands of massive galaxies or galaxy clusters. In the era of large sky surveys, an automated approach to identify ring pattern in the big data to come is in high demand. Here, we present an Einstein ring recognition approach based on computer vision techniques. The workhorse is the circle Hough transform that recognise circular patterns or arcs in the images. We propose a two-tier approach by first pre-selecting massive galaxies associated with multiple blue objects as possible lens, than use Hough transform to identify circular pattern. As a proof-of-concept, we apply our approach to SDSS, with a high completeness, albeit with low purity. We also apply our approach to other lenses in DES, HSC-SSP, and UltraVISTA survey, illustrating the versatility of our approach.

  5. 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

    BACKGROUND: Post-transcriptional RNA regulons ensure co-ordinated expression of monocistronic mRNAs encoding functionally related proteins. In this study, we employ a combination of RIP-seq and short- and long-wave individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP...

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

    Science.gov (United States)

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

    1989-04-01

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

  7. A statistical approach to identify candidate cues for nestmate recognition

    DEFF Research Database (Denmark)

    van Zweden, Jelle; Pontieri, Luigi; Pedersen, Jes Søe

    2014-01-01

    normalization, centroid,and distance calculation is most diagnostic to discriminate between NMR cues andother compounds. We find that using a “global centroid” instead of a “colony centroid”significantly improves the analysis. One reason may be that this new approach, unlikeprevious ones, provides...... than forF. exsecta, possibly due to less than ideal datasets. Nonetheless, some compound setsperformed better than others, showing that this approach can be used to identify candidatecompounds to be tested in bio-assays, and eventually crack the sophisticated code thatgoverns nestmate recognition....

  8. 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

  9. 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.

  10. 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.

  11. Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

    Science.gov (United States)

    Traglia, Michela; Tsang, Kathryn; Bearden, Carrie E.; Rauen, Katherine A.

    2017-01-01

    Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway. PMID:28076348

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Juelsgaard, Morten

    2014-01-01

    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...... may be motivated to mobilize their flexibility to obtain a trade-off between private desires, and social expenses. We discuss two conceptually different approaches for demand management, outlining their benefits and disadvantages. For this we formally present several problems concerning the central...... challenges, and demonstrate how demand management may solve these. We solve the problems using several methods based on distributed optimization, catering to the distributed nature of the resources in the grid. Our work adds to the current insight in the field of smart grids, by demonstrating how...

  16. An Efficient Approach for Identifying Stable Lobes with Discretization Method

    Directory of Open Access Journals (Sweden)

    Baohai Wu

    2013-01-01

    Full Text Available This paper presents a new approach for quick identification of chatter stability lobes with discretization method. Firstly, three different kinds of stability regions are defined: absolute stable region, valid region, and invalid region. Secondly, while identifying the chatter stability lobes, three different regions within the chatter stability lobes are identified with relatively large time intervals. Thirdly, stability boundary within the valid regions is finely calculated to get exact chatter stability lobes. The proposed method only needs to test a small portion of spindle speed and cutting depth set; about 89% computation time is savedcompared with full discretization method. It spends only about10 minutes to get exact chatter stability lobes. Since, based on discretization method, the proposed method can be used for different immersion cutting including low immersion cutting process, the proposed method can be directly implemented in the workshop to promote machining parameters selection efficiency.

  17. Quality Assurance of Cancer Study Common Data Elements Using A Post-Coordination Approach.

    Science.gov (United States)

    Jiang, Guoqian; Solbrig, Harold R; Prud'hommeaux, Eric; Tao, Cui; Weng, Chunhua; Chute, Christopher G

    2015-01-01

    Domain-specific common data elements (CDEs) are emerging as an effective approach to standards-based clinical research data storage and retrieval. A limiting factor, however, is the lack of robust automated quality assurance (QA) tools for the CDEs in clinical study domains. The objectives of the present study are to prototype and evaluate a QA tool for the study of cancer CDEs using a post-coordination approach. The study starts by integrating the NCI caDSR CDEs and The Cancer Genome Atlas (TCGA) data dictionaries in a single Resource Description Framework (RDF) data store. We designed a compositional expression pattern based on the Data Element Concept model structure informed by ISO/IEC 11179, and developed a transformation tool that converts the pattern-based compositional expressions into the Web Ontology Language (OWL) syntax. Invoking reasoning and explanation services, we tested the system utilizing the CDEs extracted from two TCGA clinical cancer study domains. The system could automatically identify duplicate CDEs, and detect CDE modeling errors. In conclusion, compositional expressions not only enable reuse of existing ontology codes to define new domain concepts, but also provide an automated mechanism for QA of terminological annotations for CDEs.

  18. New approach for identifying boundary characteristics using transmissibility

    Science.gov (United States)

    Joo, Kyung-Hoon; Min, Dongwoo; Kim, Jun-Gu; Kang, Yeon June

    2017-04-01

    A novel approach is proposed for identifying boundary properties as a response model using transmissibility. This approach differs from those proposed in previous studies dealing with frequency response functions (FRFs) for joint identification. Transmissibility includes only response data, unlike FRFs that include force measurements. The boundary properties can be estimated by comparing the characteristics of the components under the free condition and connected to boundary conditions. When analyzing the components assembled compactly in the system for setting the shaker or measuring the impact force exerted on the component correctly, the proposed method could reduce the errors caused by an incorrectly measured force. The derived equation is verified using a discrete multiple degrees of freedom system with single boundary and multiple boundary conditions and by application to a beam, which is the simplest continuous structural form to validate the feasibility of the theory. The transmissibility defined by the apparent mass matrix is used for verifying the derived equation for identifying the boundary properties in the discrete system. However, when applying the equation to practical cases, as is the purpose of this research, the transmissibility matrix should be defined using only the response data. For this purpose, the accelerance matrix is modified slightly to the response matrix using the input as a unit force. This transmissibility matrix composed of response data is used for validating the equation in a continuous system. Furthermore, the effects of measurement noise are also investigated to assess the robustness of the method for application under practical conditions. Consequently, the proposed method could show reliable results by properly extracting the boundary properties in both cases. In many practical cases, this research is expected to contribute toward identifying the boundary properties in a complex system more conveniently compared to the method

  19. Approaches to Post-Conflict Peacebuilding: The UK Post-Conflict Reconstruction Unit (PCRU) and US Office for the Coordinator of Reconstruction and Stabilization (S/CRS)

    Science.gov (United States)

    2006-09-01

    echoes the failed attempts at cookie -cutter peacekeeping of the 1990s. The key to making these assessments and planning tools viable is preserving them...interventions in the 1990s was that cookie -cutter approaches to peacebuilding were ineffectual; rather, any chance of facilitating success relied on deep...tactical-level coordination, relationship-building, and capacity- building. He identifies civil-military coordination and ’balancing carrots and

  20. Modulation of the coordination environment: a convenient approach to tailor magnetic anisotropy in seven coordinate Co(II) complexes.

    Science.gov (United States)

    Dey, Mamon; Dutta, Snigdha; Sarma, Bipul; Deka, Ramesh Ch; Gogoi, Nayanmoni

    2016-01-14

    The possibility of controlling magnetic anisotropy by tuning contribution of second order perturbation to spin-orbit coupling through modulation of the coordination environment is investigated. Subtle variation of the coordination environment triggers a remarkable deviation in the axial zero field splitting parameter of seven coordinate Co(II) complexes.

  1. 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...

  2. 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.

  3. 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...

  4. An optimized Leave One Out approach to efficiently identify outliers

    Science.gov (United States)

    Biagi, L.; Caldera, S.; Perego, D.

    2012-04-01

    Least squares are a well established and very popular statistical toolbox in geomatics. Particularly, LS are applied to routinely adjust geodetic networks in the cases both of classical surveys and of modern GNSS permanent networks, both at the local and at the global spatial scale. The linearized functional model between the observables and a vector of unknowns parameters is given. A vector of N observations and its apriori covariance is available. Typically, the observations vector can be decomposed into n subvectors, internally correlated but reciprocally uncorrelated. This happens, for example, when double differences are built from undifferenced observations and are processed to estimate the network coordinates of a GNSS session. Note that when all the observations are independent, n=N: this is for example the case of the adjustment of a levelling network. LS provide the estimates of the parameters, the observables, the residuals and of the a posteriori variance. The testing of the initial hypotheses, the rejection of outliers and the estimation of accuracies and reliabilities can be performed at different levels of significance and power. However, LS are not robust. The a posteriori estimation of the variance can be biased by one unmodelled outlier in the observations. In some case, the unmodelled bias is spread into all the residuals and its identification is difficult. A possible solution to this problem is given by the so called Leave One Out (LOO) approach. A particular subvector can be excluded from the adjustment, whose results are used to check the residuals of the excluded subvector. Clearly, the check is more robust, because a bias in the subvector does not affect the adjustment results. The process can be iterated on all the subvectors. LOO is robust but can be very slow, when n adjustments are performed. An optimized LLO algorithm has been studied. The usual LS adjustment on all the observations is performed to obtain a 'batch' result. The

  5. 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

  6. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Science.gov (United States)

    Dellagostin, Odir A.; Grassmann, André A.; Rizzi, Caroline; Schuch, Rodrigo A.; Jorge, Sérgio; Oliveira, Thais L.; McBride, Alan J. A.; Hartwig, Daiane D.

    2017-01-01

    Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins) are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV) has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis. PMID:28098813

  7. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  8. Coordination control of behavior-based distributed networked robotic systems: a state modeling approach

    Science.gov (United States)

    Kuppan Chetty, R. M.; Singaperumal, M.; Nagarajan, T.

    2007-12-01

    The coordinated motion of group of autonomous mobile robots for the achievement of goal has been of high interest since the last decade. Previous research works have revealed that one of the essential problems in the area is to plan, navigate and coordinate the motion of robots, avoiding obstacles as well as each other while still achieving the goal. In this paper, Behavior Based approach for the control of distributed networked robotic system, concentrated towards the navigation, planning and coordination between them in unknown complex environment is addressed. A layered behavior based control architecture, with the basic behaviors of Message passing, Obstacle avoidance, Safe wandering and Pit sensing have been designed and assigned to the individual robotic systems to form a navigation algorithm. Validation of this guidance algorithm is carried out through simulations using SIMULINK/State flow.

  9. 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

  10. Shared knowledge or shared affordances? Insights from an ecological dynamics approach to team coordination in sports.

    Science.gov (United States)

    Silva, Pedro; Garganta, Júlio; Araújo, Duarte; Davids, Keith; Aguiar, Paulo

    2013-09-01

    Previous research has proposed that team coordination is based on shared knowledge of the performance context, responsible for linking teammates' mental representations for collective, internalized action solutions. However, this representational approach raises many questions including: how do individual schemata of team members become reformulated together? How much time does it take for this collective cognitive process to occur? How do different cues perceived by different individuals sustain a general shared mental representation? This representational approach is challenged by an ecological dynamics perspective of shared knowledge in team coordination. We argue that the traditional shared knowledge assumption is predicated on 'knowledge about' the environment, which can be used to share knowledge and influence intentions of others prior to competition. Rather, during competitive performance, the control of action by perceiving surrounding informational constraints is expressed in 'knowledge of' the environment. This crucial distinction emphasizes perception of shared affordances (for others and of others) as the main communication channel between team members during team coordination tasks. From this perspective, the emergence of coordinated behaviours in sports teams is based on the formation of interpersonal synergies between players resulting from collective actions predicated on shared affordances.

  11. A recursive network approach can identify constitutive regulatory circuits in gene expression data

    Science.gov (United States)

    Blasi, Monica Francesca; Casorelli, Ida; Colosimo, Alfredo; Blasi, Francesco Simone; Bignami, Margherita; Giuliani, Alessandro

    2005-03-01

    The activity of the cell is often coordinated by the organisation of proteins into regulatory circuits that share a common function. Genome-wide expression profiles might contain important information on these circuits. Current approaches for the analysis of gene expression data include clustering the individual expression measurements and relating them to biological functions as well as modelling and simulation of gene regulation processes by additional computer tools. The identification of the regulative programmes from microarray experiments is limited, however, by the intrinsic difficulty of linear methods to detect low-variance signals and by the sensitivity of the different approaches. Here we face the problem of recognising invariant patterns of correlations among gene expression reminiscent of regulation circuits. We demonstrate that a recursive neural network approach can identify genetic regulation circuits from expression data for ribosomal and genome stability genes. The proposed method, by greatly enhancing the sensitivity of microarray studies, allows the identification of important aspects of genetic regulation networks and might be useful for the discrimination of the different players involved in regulation circuits. Our results suggest that the constitutive regulatory networks involved in the generic organisation of the cell display a high degree of clustering depending on a modular architecture.

  12. 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.

  13. Patterns of horse-rider coordination during endurance race: a dynamical system approach.

    Science.gov (United States)

    Viry, Sylvain; Sleimen-Malkoun, Rita; Temprado, Jean-Jacques; Frances, Jean-Philippe; Berton, Eric; Laurent, Michel; Nicol, Caroline

    2013-01-01

    In riding, most biomechanical studies have focused on the description of the horse locomotion in unridden condition. In this study, we draw the prospect of how the basic principles established in inter-personal coordination by the theory of Coordination Dynamics may provide a conceptual and methodological framework for understanding the horse-rider coupling. The recent development of mobile technologies allows combined horse and rider recordings during long lasting natural events such as endurance races. Six international horse-rider dyads were thus recorded during a 120 km race by using two tri-axial accelerometers placed on the horses and riders, respectively. The analysis concentrated on their combined vertical displacements. The obtained shapes and angles of Lissajous plots together with values of relative phase between horse and rider displacements at lower reversal point allowed us to characterize four coordination patterns, reflecting the use of two riding techniques per horse's gait (trot and canter). The present study shows that the concepts, methods and tools of self-organizing dynamic system approach offer new directions for understanding horse-rider coordination. The identification of the horse-rider coupling patterns constitutes a firm basis to further study the coalition of multiple constraints that determine their emergence and their dynamics in endurance race.

  14. Patterns of horse-rider coordination during endurance race: a dynamical system approach.

    Directory of Open Access Journals (Sweden)

    Sylvain Viry

    Full Text Available In riding, most biomechanical studies have focused on the description of the horse locomotion in unridden condition. In this study, we draw the prospect of how the basic principles established in inter-personal coordination by the theory of Coordination Dynamics may provide a conceptual and methodological framework for understanding the horse-rider coupling. The recent development of mobile technologies allows combined horse and rider recordings during long lasting natural events such as endurance races. Six international horse-rider dyads were thus recorded during a 120 km race by using two tri-axial accelerometers placed on the horses and riders, respectively. The analysis concentrated on their combined vertical displacements. The obtained shapes and angles of Lissajous plots together with values of relative phase between horse and rider displacements at lower reversal point allowed us to characterize four coordination patterns, reflecting the use of two riding techniques per horse's gait (trot and canter. The present study shows that the concepts, methods and tools of self-organizing dynamic system approach offer new directions for understanding horse-rider coordination. The identification of the horse-rider coupling patterns constitutes a firm basis to further study the coalition of multiple constraints that determine their emergence and their dynamics in endurance race.

  15. A Community-Based Approach to Identifying Influential Spreaders

    Directory of Open Access Journals (Sweden)

    Zhiying Zhao

    2015-04-01

    Full Text Available Identifying influential spreaders in complex networks has a significant impact on understanding and control of spreading process in networks. In this paper, we introduce a new centrality index to identify influential spreaders in a network based on the community structure of the network. The community-based centrality (CbC considers both the number and sizes of communities that are directly linked by a node. We discuss correlations between CbC and other classical centrality indices. Based on simulations of the single source of infection with the Susceptible-Infected-Recovered (SIR model, we find that CbC can help to identify some critical influential nodes that other indices cannot find. We also investigate the stability of CbC.

  16. An Approach for Identifying Benefit Segments among Prospective College Students.

    Science.gov (United States)

    Miller, Patrick; And Others

    1990-01-01

    A study investigated the importance to 578 applicants of various benefits offered by a moderately selective private university. Applicants rated the institution on 43 academic, social, financial, religious, and curricular attributes. The objective was to test the efficacy of one approach to college market segmentation. Results support the utility…

  17. 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...

  18. 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…

  19. Identifying Subgroups among Hardcore Smokers: a Latent Profile Approach

    NARCIS (Netherlands)

    Bommelé, J.; Kleinjan, M.; Schoenmakers, T.M.; Eijnden, R. van den; Mheen, D. van de

    2015-01-01

    Introduction: Hardcore smokers are smokers who have little to no intention to quit. Previous research suggests that there are distinct subgroups among hardcore smokers and that these subgroups vary in the perceived pros and cons of smoking and quitting. Identifying these subgroups could help to deve

  20. 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.

  1. cgaTOH: extended approach for identifying tracts of homozygosity.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available Identification of disease variants via homozygosity mapping and investigation of the effects of genome-wide homozygosity regions on traits of biomedical importance have been widely applied recently. Nonetheless, the existing methods and algorithms to identify long tracts of homozygosity (TOH are not able to provide efficient and rigorous regions for further downstream association investigation. We expanded current methods to identify TOHs by defining "surrogate-TOH", a region covering a cluster of TOHs with specific characteristics. Our defined surrogate-TOH includes cTOH, viz a common TOH region where at least ten TOHs present; gTOH, whereby a group of highly overlapping TOHs share proximal boundaries; and aTOH, which are allelically-matched TOHs. Searching for gTOH and aTOH was based on a repeated binary spectral clustering algorithm, where a hierarchy of clusters is created and represented by a TOH cluster tree. Based on the proposed method of identifying different species of surrogate-TOH, our cgaTOH software was developed. The software provides an intuitive and interactive visualization tool for better investigation of the high-throughput output with special interactive navigation rings, which will find its applicability in both conventional association studies and more sophisticated downstream analyses. NCBI genome map viewer is incorporated into the system. Moreover, we discuss the choice of implementing appropriate empirical ranges of critical parameters by applying to disease models. This method identifies various patterned clusters of SNPs demonstrating extended homozygosity, thus one can observe different aspects of the multi-faceted characteristics of TOHs.

  2. Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

    Science.gov (United States)

    Humbertjean, Lisa; Mione, Gioia; Fay, Renaud; Durin, Laurent; Planel, Sophie; Lacour, Jean-Christophe; Enea, Ana-Maria; Richard, Sébastien

    2016-03-01

    There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors.

  3. 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....

  4. 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.

  5. 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.

  6. The Motor Coordination as a Creation Device: a somatic approach in contemporary dance

    Directory of Open Access Journals (Sweden)

    Paloma

    2014-12-01

    Full Text Available This article postulates that Somatic Education integrates similar issues related to perception in both cognitive science and philosophy. It also indicates that somatic approaches can expand their area of action, overcoming their original role in health maintenance and technical improvement, to reside in the field of research and creation in dance. In order to strength the relationship between dance and somatic education, this article seeks to address some principles of Béziers and Piret’s Motor Coordination study and points out their possible unfolding in research and creation in dance through perception.

  7. Coordination of multi-agent systems under switching topologies via disturbance observer-based approach

    Science.gov (United States)

    Tang, Yutao

    2016-12-01

    In this paper, a leader-following coordination problem of heterogeneous multi-agent systems is considered under switching topologies where each agent is subject to some local (unbounded) disturbances. While these unknown disturbances may disrupt the performance of agents, a disturbance observer-based approach is employed to estimate and reject them. Varying communication topologies are also taken into consideration, and their byproduct difficulties are overcome by using common Lyapunov function techniques. According to the available information in difference cases, two disturbance observer-based protocols are proposed to solve this problem. Their effectiveness is verified by simulations.

  8. 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.

  9. 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.

  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. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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...... to be the most effective strategy to gain the best information on long-term ecosystem dynamics in response to global change....... 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...

  20. Identifying Subtypes among Children with Developmental Coordination Disorder and Mathematical Learning Disabilities, Using Model-Based Clustering

    Science.gov (United States)

    Pieters, Stefanie; Roeyers, Herbert; Rosseel, Yves; Van Waelvelde, Hilde; Desoete, Annemie

    2015-01-01

    A relationship between motor and mathematical skills has been shown by previous research. However, the question of whether subtypes can be differentiated within developmental coordination disorder (DCD) and/or mathematical learning disability (MLD) remains unresolved. In a sample of children with and without DCD and/or MLD, a data-driven…

  1. A sensorimotor approach to the training of manual actions in children with developmental coordination disorder.

    Science.gov (United States)

    Snapp-Childs, Winona; Mon-Williams, Mark; Bingham, Geoffrey P

    2013-02-01

    Developmental coordination disorder affects a relatively large proportion (5%-6%) of the childhood population. Severity of the disorder varies but there is a great need for therapeutic intervention. We propose a method for the training of manual actions in children with developmental coordination disorder. Our solution is achieved by applying haptic virtual reality technology to attack the difficulties that children with developmental coordination disorder evidence. Our results show that children with developmental coordination disorder are able to learn complex motor skills if proper training methods are employed. These findings conflict with reports of impaired motor learning in developmental coordination disorder because of underactivation of cerebellar and parietal networks.

  2. 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...

  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. Short bowel syndrome in adults: the need for an interdisciplinary approach and coordinated care.

    Science.gov (United States)

    Matarese, Laura E; Jeppesen, Palle B; O'Keefe, Stephen J D

    2014-05-01

    Short bowel syndrome (SBS) is a heterogeneous disorder with broad variation in disease severity arising from different types of intestinal resection. The spectrum of malabsorption ranges from intestinal insufficiency to intestinal failure. Individualized patient strategies involving modifications of dietary macro- and micronutrients, fluid, and pharmacologic options are required to maximize health and quality-of-life outcomes and to minimize complications and SBS-associated mortality. Intestinal rehabilitation (IR) is an established but evolving approach to improving patient outcomes by decreasing long-term dependency on parenteral support (PS) for nutrition and fluid requirements. Specialized IR programs employ team-based interdisciplinary approaches to coordinate individualized patient care and treatment management through centralized facilities. Such facilities are often specialized intestinal care centers (ICCs) established at large medical centers. A multifaceted IR program offers the comprehensive interrelated services required by patients with SBS-associated intestinal failure throughout the course of disease. Components of interdisciplinary IR programs should include medical services offering diagnostics and monitoring, pharmacologic management, and symptom and complication control; nutrition services, including dietary modifications and interventions; and supportive psychosocial and educational services. A model of care centered on the IR concept means that long-term patient management, including decisions on long-term PS, is overseen by a member of the specialized care center. Rational, seamless, and timely communication among the patient's network of home-based and ICC healthcare providers is crucial to the success of any IR program. This paradigm shift to specialized IR programs will likely result in improvements across the patient care continuum.

  5. A coordinated approach to investigating human perturbations to the Nitrogen cycle

    Science.gov (United States)

    Galloway, J. N.; Sahagian, D.

    2003-12-01

    Nitrogen is essential to the survival of all life forms yet the natural abundance of useable nitrogen is so low that massive human alteration of the nitrogen cycle has been required to sustain the feeding of the worldAŸA›A›ƒ_sAªA›ƒ_zA›s burgeoning population. The alteration has been made even greater by the release of nitrogen oxides to the atmosphere during fossil fuel combustion. Changes in the nitrogen cycle due to human action have exacerbated a number of environmental issues, including smog, acid deposition, climate change, coastal eutrophication, stratospheric ozone depletion, all of which have impacts on people and ecosystems on a regional or global basis. Because of the cascading nature of the effectAŸA›A›ƒ_sAªA›ƒ_zA›s on nitrogen, understanding of the effects, their underlying causes and their interactions must be studied in an integrated fashion from both science and policy perspectives. Toward that end, a coordinated effort is being made to integrate the diverse scientific, policy, industrial, and other stakeholder communities in an "International Nitrogen Initiative" (INI) with the goal of placing the global community in a position to optimize nitrogenAŸA›A›ƒ_sAªA›ƒ_zA›s beneficial role in sustainable food production and minimize nitrogenAŸA›A›ƒ_sAªA›ƒ_zA›s negative effects on human health and the environment resulting from food and energy production. Preliminary results suggest that novel approaches to fertilizer application can have a profound effect on excess nitrogen that enters surface and ground water, and that eutrophication of lakes and the coastal zone can be ameliorated by more efficient practices. In addition, as the processes involved in denitrification are more fully understood, it is becoming possible to better assess the partitioning of nitrogen between the ground/surface water and the atmosphere. As the coordinated study of the nitrogen cycle progresses, the assessment of nitrogen fluxes

  6. 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

  7. 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

  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.

  10. 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.

  11. A reactant-coordinate-based approach to state-to-state differential cross sections for tetratomic reactions

    Science.gov (United States)

    Zhao, Bin; Sun, Zhigang; Guo, Hua

    2016-11-01

    A new algorithm is proposed to compute quantum mechanically state-to-state differential cross sections for reactions involving four atoms in full dimensionality. This algorithm, which is based on the propagation of an initial state specific wave packet exclusively in reactant coordinates, extracts the S-matrix elements in the product channel by first interpolating the time-dependent wave packet using a collocation method at selected time intervals on the product coordinate grid and then projecting out the contributions of all final product states. This approach is efficient and accurate, particularly for reactions that are dominated by a product well or long-range interactions. Validation of this approach is demonstrated for the H2 + OH → H + H2O reaction.

  12. 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.

  13. 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.

  14. 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…

  15. 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

  16. 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.

  17. An operational modal analysis approach based on parametrically identified multivariable transmissibilities

    Science.gov (United States)

    Devriendt, Christof; De Sitter, Gert; Guillaume, Patrick

    2010-07-01

    In this contribution the approach to identify modal parameters from output-only (scalar) transmissibility measurements [C. Devriendt, P. Guillaume, The use of transmissibility measurements in output-only modal analysis, Mechanical Systems and Signal Processing 21 (7) (2007) 2689-2696] is generalized to multivariable transmissibilities. In general, the poles that are identified from (scalar as well as multivariable) transmissibility measurements do not correspond with the system's poles. However, by combining transmissibility measurements under different loading conditions, it is shown in this paper how model parameters can be identified from multivariable transmissibility measurements.

  18. The Baby TALK Model: An Innovative Approach to Identifying High-Risk Children and Families

    Science.gov (United States)

    Villalpando, Aimee Hilado; Leow, Christine; Hornstein, John

    2012-01-01

    This research report examines the Baby TALK model, an innovative early childhood intervention approach used to identify, recruit, and serve young children who are at-risk for developmental delays, mental health needs, and/or school failure, and their families. The report begins with a description of the model. This description is followed by an…

  19. A Function-First Approach to Identifying Formulaic Language in Academic Writing

    Science.gov (United States)

    Durrant, Philip; Mathews-Aydinli, Julie

    2011-01-01

    There is currently much interest in creating pedagogically-oriented descriptions of formulaic language. Research in this area has typically taken what we call a "form-first" approach, in which formulas are identified as the most frequent recurrent forms in a relevant corpus. While this research continues to yield valuable results, the present…

  20. 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…

  1. Identifying bioaccumulative halogenated organic compounds using a nontargeted analytical approach: seabirds as sentinels.

    Directory of Open Access Journals (Sweden)

    Christopher J Millow

    Full Text Available Persistent organic pollutants (POPs are typically monitored via targeted mass spectrometry, which potentially identifies only a fraction of the contaminants actually present in environmental samples. With new anthropogenic compounds continuously introduced to the environment, novel and proactive approaches that provide a comprehensive alternative to targeted methods are needed in order to more completely characterize the diversity of known and unknown compounds likely to cause adverse effects. Nontargeted mass spectrometry attempts to extensively screen for compounds, providing a feasible approach for identifying contaminants that warrant future monitoring. We employed a nontargeted analytical method using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS to characterize halogenated organic compounds (HOCs in California Black skimmer (Rynchops niger eggs. Our study identified 111 HOCs; 84 of these compounds were regularly detected via targeted approaches, while 27 were classified as typically unmonitored or unknown. Typically unmonitored compounds of note in bird eggs included tris(4-chlorophenylmethane (TCPM, tris(4-chlorophenylmethanol (TCPMOH, triclosan, permethrin, heptachloro-1'-methyl-1,2'-bipyrrole (MBP, as well as four halogenated unknown compounds that could not be identified through database searching or the literature. The presence of these compounds in Black skimmer eggs suggests they are persistent, bioaccumulative, potentially biomagnifying, and maternally transferring. Our results highlight the utility and importance of employing nontargeted analytical tools to assess true contaminant burdens in organisms, as well as to demonstrate the value in using environmental sentinels to proactively identify novel contaminants.

  2. 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.

  3. 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.

  4. 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...

  5. A Microcomputer System for Target Information in the Fire Support Coordination Center: A Data Base Approach.

    Science.gov (United States)

    1981-06-01

    DATA ASi DESIGN ....................... 74 1. Data Splittine ............................. 74 . Record Lesion . 7b 3. 7oiume and Activity Analysi5...tarret nuMber as well as by arid coordinate and a cross-index card for tne 10 to 15 target types, the target file can easily exceed 500 caras . An example...monitoring and duplicating the target list with the target Cara flies. It typically is an opportunity for the TIS staff to become very familiar with the

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  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. 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.

  13. A model-based approach to identify binding sites in CLIP-Seq data.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html, and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip for customized analysis.

  14. Identifying prognostic features by bottom-up approach and correlating to drug repositioning.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Traditionally top-down method was used to identify prognostic features in cancer research. That is to say, differentially expressed genes usually in cancer versus normal were identified to see if they possess survival prediction power. The problem is that prognostic features identified from one set of patient samples can rarely be transferred to other datasets. We apply bottom-up approach in this study: survival correlated or clinical stage correlated genes were selected first and prioritized by their network topology additionally, then a small set of features can be used as a prognostic signature.Gene expression profiles of a cohort of 221 hepatocellular carcinoma (HCC patients were used as a training set, 'bottom-up' approach was applied to discover gene-expression signatures associated with survival in both tumor and adjacent non-tumor tissues, and compared with 'top-down' approach. The results were validated in a second cohort of 82 patients which was used as a testing set.Two sets of gene signatures separately identified in tumor and adjacent non-tumor tissues by bottom-up approach were developed in the training cohort. These two signatures were associated with overall survival times of HCC patients and the robustness of each was validated in the testing set, and each predictive performance was better than gene expression signatures reported previously. Moreover, genes in these two prognosis signature gave some indications for drug-repositioning on HCC. Some approved drugs targeting these markers have the alternative indications on hepatocellular carcinoma.Using the bottom-up approach, we have developed two prognostic gene signatures with a limited number of genes that associated with overall survival times of patients with HCC. Furthermore, prognostic markers in these two signatures have the potential to be therapeutic targets.

  15. TF-Cluster: A pipeline for identifying functionally coordinated transcription factors via network decomposition of the shared coexpression connectivity matrix (SCCM

    Directory of Open Access Journals (Sweden)

    Thomson James A

    2011-04-01

    Full Text Available Abstract Background Identifying the key transcription factors (TFs controlling a biological process is the first step toward a better understanding of underpinning regulatory mechanisms. However, due to the involvement of a large number of genes and complex interactions in gene regulatory networks, identifying TFs involved in a biological process remains particularly difficult. The challenges include: (1 Most eukaryotic genomes encode thousands of TFs, which are organized in gene families of various sizes and in many cases with poor sequence conservation, making it difficult to recognize TFs for a biological process; (2 Transcription usually involves several hundred genes that generate a combination of intrinsic noise from upstream signaling networks and lead to fluctuations in transcription; (3 A TF can function in different cell types or developmental stages. Currently, the methods available for identifying TFs involved in biological processes are still very scarce, and the development of novel, more powerful methods is desperately needed. Results We developed a computational pipeline called TF-Cluster for identifying functionally coordinated TFs in two steps: (1 Construction of a shared coexpression connectivity matrix (SCCM, in which each entry represents the number of shared coexpressed genes between two TFs. This sparse and symmetric matrix embodies a new concept of coexpression networks in which genes are associated in the context of other shared coexpressed genes; (2 Decomposition of the SCCM using a novel heuristic algorithm termed "Triple-Link", which searches the highest connectivity in the SCCM, and then uses two connected TF as a primer for growing a TF cluster with a number of linking criteria. We applied TF-Cluster to microarray data from human stem cells and Arabidopsis roots, and then demonstrated that many of the resulting TF clusters contain functionally coordinated TFs that, based on existing literature, accurately represent

  16. A cellular genetics approach identifies gene-drug interactions and pinpoints drug toxicity pathway nodes

    Directory of Open Access Journals (Sweden)

    Oscar Takeo Suzuki

    2014-08-01

    Full Text Available New approaches to toxicity testing have incorporated high-throughput screening across a broad-range of in vitro assays to identify potential key events in response to chemical or drug treatment. To date, these approaches have primarily utilized repurposed drug discovery assays. In this study, we describe an approach that combines in vitro screening with genetic approaches for the experimental identification of genes and pathways involved in chemical or drug toxicity. Primary embryonic fibroblasts isolated from 32 genetically-characterized inbred mouse strains were treated in concentration-response format with 65 compounds, including pharmaceutical drugs, environmental chemicals, and compounds with known modes-of-action. Integrated cellular responses were measured at 24 and 72 hours using high-content imaging and included cell loss, membrane permeability, mitochondrial function, and apoptosis. Genetic association analysis of cross-strain differences in the cellular responses resulted in a collection of candidate loci potentially underlying the variable strain response to each chemical. As a demonstration of the approach, one candidate gene involved in rotenone sensitivity, Cybb, was experimentally validated in vitro and in vivo. Pathway analysis on the combined list of candidate loci across all chemicals identified a number of over-connected nodes that may serve as core regulatory points in toxicity pathways.

  17. 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

  18. 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.

  19. Constructing New Theory for Identifying Students with Emotional Disturbance: A Constructivist Approach to Grounded Theory

    OpenAIRE

    2012-01-01

    A grounded theory study that examined how practitioners in a county alternative and correctional education setting identify youth with emotional and behavioral difficulties for special education services provides an exemplar for a constructivist approach to grounded theory methodology. Discussion focuses on how a constructivist orientation to grounded theory methodology informed research decisions, shaped the development of the emergent grounded theory, and prompted a way of thinking about da...

  20. An Approach to Identify and Characterize a Subunit Candidate Shigella Vaccine Antigen.

    Science.gov (United States)

    Pore, Debasis; Chakrabarti, Manoj K

    2016-01-01

    Shigellosis remains a serious issue throughout the developing countries, particularly in children under the age of 5. Numerous strategies have been tested to develop vaccines targeting shigellosis; unfortunately despite several years of extensive research, no safe, effective, and inexpensive vaccine against shigellosis is available so far. Here, we illustrate in detail an approach to identify and establish immunogenic outer membrane proteins from Shigella flexneri 2a as subunit vaccine candidates.

  1. 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.

  2. 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.

  3. 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.

  4. Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies.

    Science.gov (United States)

    Mueller, Alan J; Peffers, Mandy J; Proctor, Carole J; Clegg, Peter D

    2017-03-20

    Systems orientated research offers the possibility of identifying novel therapeutic targets and relevant diagnostic markers for complex diseases such as osteoarthritis. This review demonstrates that the osteoarthritis research community has been slow to incorporate systems orientated approaches into research studies, although a number of key studies reveal novel insights into the regulatory mechanisms that contribute both to joint tissue homeostasis and its dysfunction. The review introduces both top-down and bottom-up approaches employed in the study of osteoarthritis. A holistic and multiscale approach, where clinical measurements may predict dysregulation and progression of joint degeneration, should be a key objective in future research. The review concludes with suggestions for further research and emerging trends not least of which is the coupled development of diagnostic tests and therapeutics as part of a concerted effort by the osteoarthritis research community to meet clinical needs. This article is protected by copyright. All rights reserved.

  5. 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

  6. Identifying and assessing the application of ecosystem services approaches in environmental policies and decision making.

    Science.gov (United States)

    Van Wensem, Joke; Calow, Peter; Dollacker, Annik; Maltby, Lorraine; Olander, Lydia; Tuvendal, Magnus; Van Houtven, George

    2017-01-01

    The presumption is that ecosystem services (ES) approaches provide a better basis for environmental decision making than do other approaches because they make explicit the connection between human well-being and ecosystem structures and processes. However, the existing literature does not provide a precise description of ES approaches for environmental policy and decision making, nor does it assess whether these applications will make a difference in terms of changing decisions and improving outcomes. We describe 3 criteria that can be used to identify whether and to what extent ES approaches are being applied: 1) connect impacts all the way from ecosystem changes to human well-being, 2) consider all relevant ES affected by the decision, and 3) consider and compare the changes in well-being of different stakeholders. As a demonstration, we then analyze retrospectively whether and how the criteria were met in different decision-making contexts. For this assessment, we have developed an analysis format that describes the type of policy, the relevant scales, the decisions or questions, the decision maker, and the underlying documents. This format includes a general judgment of how far the 3 ES criteria have been applied. It shows that the criteria can be applied to many different decision-making processes, ranging from the supranational to the local scale and to different parts of decision-making processes. In conclusion we suggest these criteria could be used for assessments of the extent to which ES approaches have been and should be applied, what benefits and challenges arise, and whether using ES approaches made a difference in the decision-making process, decisions made, or outcomes of those decisions. Results from such studies could inform future use and development of ES approaches, draw attention to where the greatest benefits and challenges are, and help to target integration of ES approaches into policies, where they can be most effective. Integr Environ

  7. 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.

  8. 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.

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

    Institute of Scientific and Technical Information of China (English)

    张力

    2014-01-01

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

  10. Identifying comorbid depression and disruptive behavior disorders: comparison of two approaches used in adolescent studies.

    Science.gov (United States)

    Vander Stoep, Ann; Adrian, Molly C; Rhew, Isaac C; McCauley, Elizabeth; Herting, Jerald R; Kraemer, Helena C

    2012-07-01

    Interest in commonly co-occurring depression and disruptive behavior disorders in children has yielded a small body of research that estimates the prevalence of this comorbid condition and compares children with the comorbid condition and children with depression or disruptive behavior disorders alone with respect to antecedents and outcomes. Prior studies have used one of two different approaches to measure comorbid disorders: (1) meeting criteria for two DSM or ICD diagnoses or (2) scoring .5 SD above the mean or higher on two dimensional scales. This study compares two snapshots of comorbidity taken simultaneously in the same sample with each of the measurement approaches. The Developmental Pathways Project administered structured diagnostic interviews as well as dimensional scales to a community-based sample of 521 11-12 year olds to assess depression and disruptive behavior disorders. Clinical caseness indicators of children identified as "comorbid" by each method were examined concurrently and 3-years later. Cross-classification of adolescents via the two approaches revealed low agreement. When other indicators of caseness, including functional impairment, need for services, and clinical elevations on other symptom scales were examined, adolescents identified as comorbid via dimensional scales only were similar to those who were identified as comorbid via DSM-IV diagnostic criteria. Findings suggest that when relying solely on DSM diagnostic criteria for comorbid depression and disruptive behavior disorders, many adolescents with significant impairment will be overlooked. Findings also suggest that lower dimensional scale thresholds can be set when comorbid conditions, rather than single forms of psychopathology, are being identified.

  11. Translational informatics approach for identifying the functional molecular communicators linking coronary artery disease, infection and inflammation.

    Science.gov (United States)

    Sharma, Ankit; Ghatge, Madankumar; Mundkur, Lakshmi; Vangala, Rajani Kanth

    2016-05-01

    Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD‑gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)‑induced genes were identified from the literature and the CAD‑associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identified in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ‑glutamyl transferase (GGT)‑5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV‑neutralizing antibody (CMV‑NA) titers. The C‑statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction.

  12. 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...

  13. 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.

  14. Improving accuracy for identifying related PubMed queries by an integrated approach.

    Science.gov (United States)

    Lu, Zhiyong; Wilbur, W John

    2009-10-01

    PubMed is the most widely used tool for searching biomedical literature online. As with many other online search tools, a user often types a series of multiple related queries before retrieving satisfactory results to fulfill a single information need. Meanwhile, it is also a common phenomenon to see a user type queries on unrelated topics in a single session. In order to study PubMed users' search strategies, it is necessary to be able to automatically separate unrelated queries and group together related queries. Here, we report a novel approach combining both lexical and contextual analyses for segmenting PubMed query sessions and identifying related queries and compare its performance with the previous approach based solely on concept mapping. We experimented with our integrated approach on sample data consisting of 1539 pairs of consecutive user queries in 351 user sessions. The prediction results of 1396 pairs agreed with the gold-standard annotations, achieving an overall accuracy of 90.7%. This demonstrates that our approach is significantly better than the previously published method. By applying this approach to a one day query log of PubMed, we found that a significant proportion of information needs involved more than one PubMed query, and that most of the consecutive queries for the same information need are lexically related. Finally, the proposed PubMed distance is shown to be an accurate and meaningful measure for determining the contextual similarity between biological terms. The integrated approach can play a critical role in handling real-world PubMed query log data as is demonstrated in our experiments.

  15. 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.

  16. Identifying overlapping and hierarchical thematic structures in networks of scholarly papers: a comparison of three approaches.

    Directory of Open Access Journals (Sweden)

    Frank Havemann

    Full Text Available 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.

  17. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  19. 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.

  20. Constructing New Theory for Identifying Students with Emotional Disturbance: A Constructivist Approach to Grounded Theory

    Directory of Open Access Journals (Sweden)

    Dori Barnett

    2012-06-01

    Full Text Available A grounded theory study that examined how practitioners in a county alternative and correctional education setting identify youth with emotional and behavioral difficulties for special education services provides an exemplar for a constructivist approach to grounded theory methodology. Discussion focuses on how a constructivist orientation to grounded theory methodology informed research decisions, shaped the development of the emergent grounded theory, and prompted a way of thinking about data collection and analysis. Implications for future research directions and policy and practice in the field of special and alternative education are discussed.

  1. 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.

  2. 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

    2015-02-02

    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.

  3. 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…

  4. 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.

  5. A systematic approach for identifying and presenting mechanistic evidence in human health assessments

    Science.gov (United States)

    Kushman, Mary E.; Kraft, Andrew D.; Guyton, Kathryn Z.; Chiu, Weihsueh A.; Makris, Susan L.; Rusyn, Ivan

    2013-01-01

    Clear documentation of literature search and presentation methodologies can improve transparency in chemical hazard assessments. We sought to improve clarity for the scientific support for cancer mechanisms of action using a systematic approach to literature retrieval, selection, and presentation of studies. The general question was “What are the mechanisms by which a chemical may cause carcinogenicity in the target tissue?” Di(2-ethylhexyl)phthalate was used as a case study chemical with a complex database of >3,000 publications. Relevant mechanistic events were identified from published reviews. The PubMed search strategy included relevant synonyms and wildcards for DEHP and its metabolites, mechanistic events, and species of interest. Tiered exclusion/inclusion criteria for study pertinence were defined, and applied to the retrieved literature. Manual curation was conducted for mechanistic events with large literature databases. Literature trees documented identification and selection of the literature evidence. The selected studies were summarized in evidence tables accompanied by succinct narratives. Primary publications were deposited into the Health and Environmental Research Online (http://hero.epa.gov/) database and identified by pertinence criteria and key terms to permit organized retrieval. This approach contributes to human health assessment by effectively managing a large volume of literature, improving transparency, and facilitating subsequent synthesis of information across studies. PMID:23959061

  6. Identifying ligands at orphan GPCRs: current status using structure-based approaches.

    Science.gov (United States)

    Ngo, Tony; Kufareva, Irina; Coleman, James Lj; Graham, Robert M; Abagyan, Ruben; Smith, Nicola J

    2016-10-01

    GPCRs are the most successful pharmaceutical targets in history. Nevertheless, the pharmacology of many GPCRs remains inaccessible as their endogenous or exogenous modulators have not been discovered. Tools that explore the physiological functions and pharmacological potential of these 'orphan' GPCRs, whether they are endogenous and/or surrogate ligands, are therefore of paramount importance. Rates of receptor deorphanization determined by traditional reverse pharmacology methods have slowed, indicating a need for the development of more sophisticated and efficient ligand screening approaches. Here, we discuss the use of structure-based ligand discovery approaches to identify small molecule modulators for exploring the function of orphan GPCRs. These studies have been buoyed by the growing number of GPCR crystal structures solved in the past decade, providing a broad range of template structures for homology modelling of orphans. This review discusses the methods used to establish the appropriate signalling assays to test orphan receptor activity and provides current examples of structure-based methods used to identify ligands of orphan GPCRs. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

  7. 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.

  8. 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....

  9. Movement Coordination in Human-Robot Teams: A Dynamical Systems Approach

    OpenAIRE

    Iqbal, Tariq; Rack, Samantha; Riek, Laurel D.

    2016-01-01

    In order to be effective teammates, robots need to be able to understand high-level human behavior to recognize, anticipate, and adapt to human motion. We have designed a new approach to enable robots to perceive human group motion in real-time, anticipate future actions, and synthesize their own motion accordingly. We explore this within the context of joint action, where humans and robots move together synchronously. In this paper, we present an anticipation method which takes high-level gr...

  10. The Motor Coordination as a Creation Device: a somatic approach in contemporary dance

    OpenAIRE

    Paloma; Sandra De Meyer

    2014-01-01

    This article postulates that Somatic Education integrates similar issues related to perception in both cognitive science and philosophy. It also indicates that somatic approaches can expand their area of action, overcoming their original role in health maintenance and technical improvement, to reside in the field of research and creation in dance. In order to strength the relationship between dance and somatic education, this article seeks to address some principles of Béziers and Piret’s ...

  11. A Convective Coordinate Approach to Continuum Mechanics with Application to Electrodynamics

    Science.gov (United States)

    2013-01-01

    nonunique theories may be constructed via other means; this is the approach taken here to illustrate the convective form of reference 3. This work aimed to... Engineering ; Springer-Verlag: Berlin, 1984. 12. Truesdell, C.; Noll, W. The non-linear field theories of mechanics. In Encyclopedia of Physics; Vol. 3... ENGINEERS USACEGSL P PAPADOS 7701 TELEGRAPH RD ALEXANDRIA VA 22315 5 DIRECTOR LANL P MAUDLIN R GRAY W R THISSELL A ZUREK F ADDESSIO PO BOX 1663 LOS ALAMOS NM

  12. 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.

  13. 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.

  14. Evaluation of approaches to identify the targets of cellular immunity on a proteome-wide scale.

    Directory of Open Access Journals (Sweden)

    Fernanda C Cardoso

    Full Text Available BACKGROUND: Vaccine development against malaria and other complex diseases remains a challenge for the scientific community. The recent elucidation of the genome, proteome and transcriptome of many of these complex pathogens provides the basis for rational vaccine design by identifying, on a proteome-wide scale, novel target antigens that are recognized by T cells and antibodies from exposed individuals. However, there is currently no algorithm to effectively identify important target antigens from genome sequence data; this is especially challenging for T cell targets. Furthermore, for some of these pathogens, such as Plasmodium, protein expression using conventional platforms has been problematic but cell-free in vitro transcription translation (IVTT strategies have recently proved successful. Herein, we report a novel approach for proteome-wide scale identification of the antigenic targets of T cell responses using IVTT products. PRINCIPAL FINDINGS: We conducted a series of in vitro and in vivo experiments using IVTT proteins either unpurified, absorbed to carboxylated polybeads, or affinity purified through nickel resin or magnetic beads. In vitro studies in humans using CMV, EBV, and Influenza A virus proteins showed antigen-specific cytokine production in ELIspot and Cytometric Bead Array assays with cells stimulated with purified or unpurified IVTT antigens. In vitro and in vivo studies in mice immunized with the Plasmodium yoelii circumsporozoite DNA vaccine with or without IVTT protein boost showed antigen-specific cytokine production using purified IVTT antigens only. Overall, the nickel resin method of IVTT antigen purification proved optimal in both human and murine systems. CONCLUSIONS: This work provides proof of concept for the potential of high-throughput approaches to identify T cell targets of complex parasitic, viral or bacterial pathogens from genomic sequence data, for rational vaccine development against emerging and re

  15. Identifying functional reorganization of spelling networks: an individual peak probability comparison approach.

    Science.gov (United States)

    Purcell, Jeremy J; Rapp, Brenda

    2013-01-01

    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.

  16. 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

  17. COORDINATED LOCATION, DISTRIBUTION AND INVENTORY DECISIONS IN SUPPLY CHAIN NETWORK DESIGN: A MULTI-OBJECTIVE APPROACH

    Directory of Open Access Journals (Sweden)

    G. Reza Nasiri

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: This research presents an integrated multi-objective distribution model for use in simultaneous strategic and operational food supply chain (SC planning. The proposed method is adopted to allow use of a performance measurement system that includes conflicting objectives such as distribution costs, customer service level (safety stock holding, resource utilisation, and the total delivery time, with reference to multiple warehouse capacities and uncertain forecast demands. To deal with these objectives and enable the decision makers (DMs to evaluate a greater number of alternative solutions, three different approaches are implemented in the proposed solution procedure. A detailed case study derived from food industrial data is used to illustrate the preference of the proposed approach. The proposed method yields an efficient solution and an overall degree of DMs’ satisfaction with the determined objective values.

    AFRIKAANSE OPSOMMING: Die navorsing behandel ’n geïntegreerde multidoelwit distribusiemodel vir strategiese beplanning van ’n voedseltoevoerketting. Om met die model doelmatig te werk, moet ’n versameling van randvoorwaardes hanteer word om die saamgestelde optimiseringsdoelwit te bereik teen ’n agtergrond van uiteenlopende sienings.

  18. 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.

  19. The basis for improving and reforming long-term care. Part 4: identifying meaningful improvement approaches (segment 2).

    Science.gov (United States)

    Levenson, Steven A

    2010-03-01

    While many aspects of nursing home care have improved over time, numerous issues persist. Presently, a potpourri of approaches and a push to "fix" the problem have overshadowed efforts to correctly define the problems and identify their diverse causes. This fourth and final article in the series (divided between last month's issue and this one) recommends strategies to make sense of improvement and reform efforts. This month's concluding segment covers additional proposed approaches. Despite the challenges of the current environment, all of the proposed strategies could potentially be applied with little or no delay. Despite having brought vast increases in knowledge, the research effort may be losing its traction as a formidable force for meaningful change. It is necessary to rethink the questions being asked and the scope of answers being sought. A shift to overcoming implementation challenges is needed. In addition, it is essential to address issues of jurisdiction (the apparent "ownership" of assessment and decision making over patient problems or body parts) and reductionism (the excessive management of these issues and problems without proper context) that result in fragmented and problematic care. Issues of knowledge and skill also need to be addressed, with greater emphasis on key generic and technical competencies of staff and practitioners, in addition to factual knowledge. There is a need to rethink the approach to measuring performance and trying to improve quality of care and services. There are significant limits to trying to use quality measures to improve outcomes and performance. Ultimately, vast improvement is needed in applying care principles and practices, independent of regulatory sources. Reimbursement needs to be revamped so that it helps promote care that is consistent with human biology and other key concepts. Finally, improving long-term care will require a coordinated societal effort. All social institutions and health care settings need

  20. 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.

  1. 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

  2. An interdisciplinary approach to identify adaptation strategies that enhance flood resilience and urban liveability

    DEFF Research Database (Denmark)

    Rogers, B. C.; Bertram, N.; Gunn, Alex;

    This paper provides guidance on how to identify and design the most suitable climate adaptation strategies for enhancing the liveability and flood resilience of urban catchments. It presents findings from a case study of Elwood, a coastal Melbourne suburb regularly affected by flooding....... The research integrates social science, architecture and environmental engineering to co-develop technical, design and policy solutions that respond to the local community’s vision for the future and are robust under a range of future climate, population and urban development scenarios. The paper shows...... that ensuring a city’s flood resilience involves a range of measures to retreat from, adapt to and defend against flooding; this necessarily requires an integrated approach and interdisciplinary expertise to develop adaptation pathways that are grounded in community aspirations and priorities, inspired by novel...

  3. 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

  4. Toward an efficient approach to identify molecular scaffolds possessing selective or promiscuous compounds.

    Science.gov (United States)

    Yongye, Austin B; Medina-Franco, José L

    2013-10-01

    The concept of a recurrent scaffold present in a series of structures is common in medicinal drug discovery. We present a scaffold analysis of compounds screened across 100 sequence-unrelated proteins to identify scaffolds that drive promiscuity or selectivity. Selectivity and promiscuity play a major role in traditional and poly-pharmacological drug design considerations. The collection employed here is the first publicly available data set containing the complete screening profiles of more than 15 000 compounds from different sources. In addition, no scaffold analysis of this data set has been reported. The protocol described here employs the Molecular Equivalence Index tool to facilitate the selection of Bemis-Murcko frameworks in the data set, which contain at least five compounds and Scaffold Hunter to generate a hierarchical tree of scaffolds. The annotation of the scaffold tree with protein-binding profile data enabled the successful identification of mostly highly specific compounds, due to data set constraints. We also applied this approach to a public set of 1497 small molecules screened non-uniformly across a panel of 172 protein kinases. The approach is general and can be applied to any other data sets and activity readout.

  5. 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.

  6. New approach for identifying the zero-order fringe in variable wavelength interferometry

    Science.gov (United States)

    Galas, Jacek; Litwin, Dariusz; Daszkiewicz, Marek

    2016-12-01

    The family of VAWI techniques (for transmitted and reflected light) is especially efficient for characterizing objects, when in the interference system the optical path difference exceeds a few wavelengths. The classical approach that consists in measuring the deflection of interference fringes fails because of strong edge effects. Broken continuity of interference fringes prevents from correct identification of the zero order fringe, which leads to significant errors. The family of these methods has been proposed originally by Professor Pluta in the 1980s but that time image processing facilities and computers were hardly available. Automated devices unfold a completely new approach to the classical measurement procedures. The Institute team has taken that new opportunity and transformed the technique into fully automated measurement devices offering commercial readiness of industry-grade quality. The method itself has been modified and new solutions and algorithms simultaneously have extended the field of application. This has concerned both construction aspects of the systems and software development in context of creating computerized instruments. The VAWI collection of instruments constitutes now the core of the Institute commercial offer. It is now practically applicable in industrial environment for measuring textile and optical fibers, strips of thin films, testing of wave plates and nonlinear affects in different materials. This paper describes new algorithms for identifying the zero order fringe, which increases the performance of the system as a whole and presents some examples of measurements of optical elements.

  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.

  8. The waveform similarity approach to identify dependent events in instrumental seismic catalogues

    Science.gov (United States)

    Barani, S.; Ferretti, G.; Massa, M.; Spallarossa, D.

    2007-01-01

    In this paper, waveform similarity analysis is adapted and implemented in a declustering procedure to identify foreshocks and aftershocks, to obtain instrumental catalogues that are cleaned of dependent events and to perform an independent check of the results of traditional declustering techniques. Unlike other traditional declustering methods (i.e. windowing techniques), the application of cross-correlation analysis allows definition of groups of dependent events (multiplets) characterized by similar location, fault mechanism and propagation pattern. In this way the chain of intervening related events is led by the seismogenetic features of earthquakes. Furthermore, a time-selection criterion is used to define time-independent seismic episodes eventually joined (on the basis of waveform similarity) into a single multiplet. The results, obtained applying our procedure to a test data set, show that the declustered catalogue is drawn by the Poisson distribution with a degree of confidence higher than using the Gardner and Knopoff method. The declustered catalogues, applying these two approaches, are similar with respect to the frequency-magnitude distribution and the number of earthquakes. Nevertheless, the application of our approach leads to declustered catalogues properly related to the seismotectonic background and the reology of the investigated area and the success of the procedure is ensured by the independence of the results on estimated location errors of the events collected in the raw catalogue.

  9. 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.

  10. An integrated approach for identifying wrongly labelled samples when performing classification in microarray data.

    Directory of Open Access Journals (Sweden)

    Yuk Yee Leung

    Full Text Available BACKGROUND: Using hybrid approach for gene selection and classification is common as results obtained are generally better than performing the two tasks independently. Yet, for some microarray datasets, both classification accuracy and stability of gene sets obtained still have rooms for improvement. This may be due to the presence of samples with wrong class labels (i.e. outliers. Outlier detection algorithms proposed so far are either not suitable for microarray data, or only solve the outlier detection problem on their own. RESULTS: We tackle the outlier detection problem based on a previously proposed Multiple-Filter-Multiple-Wrapper (MFMW model, which was demonstrated to yield promising results when compared to other hybrid approaches (Leung and Hung, 2010. To incorporate outlier detection and overcome limitations of the existing MFMW model, three new features are introduced in our proposed MFMW-outlier approach: 1 an unbiased external Leave-One-Out Cross-Validation framework is developed to replace internal cross-validation in the previous MFMW model; 2 wrongly labeled samples are identified within the MFMW-outlier model; and 3 a stable set of genes is selected using an L1-norm SVM that removes any redundant genes present. Six binary-class microarray datasets were tested. Comparing with outlier detection studies on the same datasets, MFMW-outlier could detect all the outliers found in the original paper (for which the data was provided for analysis, and the genes selected after outlier removal were proven to have biological relevance. We also compared MFMW-outlier with PRAPIV (Zhang et al., 2006 based on same synthetic datasets. MFMW-outlier gave better average precision and recall values on three different settings. Lastly, artificially flipped microarray datasets were created by removing our detected outliers and flipping some of the remaining samples' labels. Almost all the 'wrong' (artificially flipped samples were detected, suggesting

  11. Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

    Science.gov (United States)

    Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

    2012-01-01

    Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. A phase coherence approach to identifying co-located earthquakes and tremor

    Science.gov (United States)

    Hawthorne, J. C.; Ampuero, J.-P.

    2017-01-01

    We present and use a phase coherence approach to identify seismic signals that have similar path effects but different source time functions: co-located earthquakes and tremor. The method used is a phase coherence-based implementation of empirical matched field processing, modified to suit tremor analysis. It works by comparing the frequency-domain phases of waveforms generated by two sources recorded at multiple stations. We first cross-correlate the records of the two sources at a single station. If the sources are co-located, this cross-correlation eliminates the phases of the Green's function. It leaves the relative phases of the source time functions, which should be the same across all stations so long as the spatial extent of the sources are small compared with the seismic wavelength. We therefore search for cross-correlation phases that are consistent across stations as an indication of co-located sources. We also introduce a method to obtain relative locations between the two sources, based on back-projection of inter-station phase coherence. We apply this technique to analyze two tremor-like signals that are thought to be composed of a number of earthquakes. First, we analyze a 20-second-long seismic precursor to a M 3.9 earthquake in central Alaska. The analysis locates the precursor to within 2 km of the mainshock, and it identifies several bursts of energy-potentially foreshocks or groups of foreshocks-within the precursor. Second, we examine several minutes of volcanic tremor prior to an eruption at Redoubt Volcano. We confirm that the tremor source is located close to repeating earthquakes identified earlier in the tremor sequence. The amplitude of the tremor diminishes about 30 seconds before the eruption, but the phase coherence results suggest that the tremor may persist at some level through this final interval.

  19. 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.

  20. Reaction Coordinates and Mechanistic Hypothesis Tests

    Science.gov (United States)

    Peters, Baron

    2016-05-01

    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.

  1. Enabling children with Developmental Coordination Disorder to self-regulate through the use of Dynamic Performance Analysis: evidence from the CO-OP approach.

    Science.gov (United States)

    Hyland, M; Polatajko, H J

    2012-08-01

    Anecdotal evidence suggests that Dynamic Performance Analysis (DPA) is learned by children with Developmental Coordination Disorder (DCD) during Cognitive Orientation to Occupational Performance (CO-OP) intervention. DPA is a tool used by therapists during the CO-OP approach to identify performance breakdowns and strategies for skill acquisition. This suggests that the self-regulation difficulties experienced by these children are amenable to intervention. The purpose of this proof of principle study was to determine: if school-aged children with DCD carry out DPAs, if DPA use was positively affected by intervention, and whether CO-OP had a larger effect on DPA use. Previously recorded videos of 13 children with DCD undergoing CO-OP, contemporary treatment or task-specific training were analyzed for evidence of DPA use. It was found that children in all three groups used simple DPAs before intervention; those receiving CO-OP intervention dramatically increased the number and quality of DPAs and could spontaneously apply it to the performance of another child. These findings indicate that, despite issues of self-regulation, children with DCD do self-monitor performance. More importantly, this ability can improve with CO-OP intervention as it guides the discovery of self-identified performance solutions, thereby enabling skill acquisition, generalization and transfer.

  2. 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 t......, 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.......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...

  3. Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.

    Science.gov (United States)

    Patel, Nisha; Anand, Deepti; Monies, Dorota; Maddirevula, Sateesh; Khan, Arif O; Algoufi, Talal; Alowain, Mohammed; Faqeih, Eissa; Alshammari, Muneera; Qudair, Ahmed; Alsharif, Hadeel; Aljubran, Fatimah; Alsaif, Hessa S; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alsedairy, Haifa; Aldahmesh, Mohammed A; Lachke, Salil A; Alkuraya, Fowzan S

    2017-02-01

    Pediatric cataract is highly heterogeneous clinically and etiologically. While mostly isolated, cataract can be part of many multisystem disorders, further complicating the diagnostic process. In this study, we applied genomic tools in the form of a multi-gene panel as well as whole-exome sequencing on unselected cohort of pediatric cataract (166 patients from 74 families). Mutations in previously reported cataract genes were identified in 58% for a total of 43 mutations, including 15 that are novel. GEMIN4 was independently mutated in families with a syndrome of cataract, global developmental delay with or without renal involvement. We also highlight a recognizable syndrome that resembles galactosemia (a fulminant infantile liver disease with cataract) caused by biallelic mutations in CYP51A1. A founder mutation in RIC1 (KIAA1432) was identified in patients with cataract, brain atrophy, microcephaly with or without cleft lip and palate. For non-syndromic pediatric cataract, we map a novel locus in a multiplex consanguineous family on 4p15.32 where exome sequencing revealed a homozygous truncating mutation in TAPT1. We report two further candidates that are biallelically inactivated each in a single cataract family: TAF1A (cataract with global developmental delay) and WDR87 (non-syndromic cataract). In addition to positional mapping data, we use iSyTE developmental lens expression and gene-network analysis to corroborate the proposed link between the novel candidate genes and cataract. Our study expands the phenotypic, allelic and locus heterogeneity of pediatric cataract. The high diagnostic yield of clinical genomics supports the adoption of this approach in this patient group.

  4. 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

  5. Identifying contamination with advanced visualization and analysis practices: metagenomic approaches for eukaryotic genome assemblies

    Science.gov (United States)

    Delmont, Tom O.

    2016-01-01

    High-throughput sequencing provides a fast and cost-effective mean to recover genomes of organisms from all domains of life. However, adequate curation of the assembly results against potential contamination of non-target organisms requires advanced bioinformatics approaches and practices. Here, we re-analyzed the sequencing data generated for the tardigrade Hypsibius dujardini, and created a holistic display of the eukaryotic genome assembly using DNA data originating from two groups and eleven sequencing libraries. By using bacterial single-copy genes, k-mer frequencies, and coverage values of scaffolds we could identify and characterize multiple near-complete bacterial genomes from the raw assembly, and curate a 182 Mbp draft genome for H. dujardini supported by RNA-Seq data. Our results indicate that most contaminant scaffolds were assembled from Moleculo long-read libraries, and most of these contaminants have differed between library preparations. Our re-analysis shows that visualization and curation of eukaryotic genome assemblies can benefit from tools designed to address the needs of today’s microbiologists, who are constantly challenged by the difficulties associated with the identification of distinct microbial genomes in complex environmental metagenomes. PMID:27069789

  6. 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.

  7. 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.

  8. 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

    2016-06-02

    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.

  9. 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

  10. Identifying medication error chains from critical incident reports: a new analytic approach.

    Science.gov (United States)

    Huckels-Baumgart, Saskia; Manser, Tanja

    2014-10-01

    Research into the distribution of medication errors usually focuses on isolated stages within the medication use process. Our study aimed to provide a novel process-oriented approach to medication incident analysis focusing on medication error chains. Our study was conducted across a 900-bed teaching hospital in Switzerland. All reported 1,591 medication errors 2009-2012 were categorized using the Medication Error Index NCC MERP and the WHO Classification for Patient Safety Methodology. In order to identify medication error chains, each reported medication incident was allocated to the relevant stage of the hospital medication use process. Only 25.8% of the reported medication errors were detected before they propagated through the medication use process. The majority of medication errors (74.2%) formed an error chain encompassing two or more stages. The most frequent error chain comprised preparation up to and including medication administration (45.2%). "Non-consideration of documentation/prescribing" during the drug preparation was the most frequent contributor for "wrong dose" during the administration of medication. Medication error chains provide important insights for detecting and stopping medication errors before they reach the patient. Existing and new safety barriers need to be extended to interrupt error chains and to improve patient safety.

  11. Identifying contamination with advanced visualization and analysis practices: metagenomic approaches for eukaryotic genome assemblies

    Directory of Open Access Journals (Sweden)

    Tom O. Delmont

    2016-03-01

    Full Text Available High-throughput sequencing provides a fast and cost-effective mean to recover genomes of organisms from all domains of life. However, adequate curation of the assembly results against potential contamination of non-target organisms requires advanced bioinformatics approaches and practices. Here, we re-analyzed the sequencing data generated for the tardigrade Hypsibius dujardini, and created a holistic display of the eukaryotic genome assembly using DNA data originating from two groups and eleven sequencing libraries. By using bacterial single-copy genes, k-mer frequencies, and coverage values of scaffolds we could identify and characterize multiple near-complete bacterial genomes from the raw assembly, and curate a 182 Mbp draft genome for H. dujardini supported by RNA-Seq data. Our results indicate that most contaminant scaffolds were assembled from Moleculo long-read libraries, and most of these contaminants have differed between library preparations. Our re-analysis shows that visualization and curation of eukaryotic genome assemblies can benefit from tools designed to address the needs of today’s microbiologists, who are constantly challenged by the difficulties associated with the identification of distinct microbial genomes in complex environmental metagenomes.

  12. A statistical approach for identifying nuclear waste glass compositions that will meet quality and processability requirements

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, G.F.

    1990-09-01

    Borosilicate glass provides a solid, stable medium for the disposal of high-level radioactive wastes resulting from the production of nuclear materials for United States defense needs. The glass must satisfy various quality and processability requirements on properties such as chemical durability, viscosity, and electrical conductivity. These properties depend on the composition of the waste glass, which will vary during production due to variations in nuclear waste composition and variations in the glass-making process. This paper discusses the experimentally-based statistical approach being used in the Hanford Waste Vitrification Plant (HWVP) Composition Variability Study (CVS). The overall goal of the CVS is to identify the composition region of potential HWVP waste glasses that satisfy with high confidence the applicable quality and processability requirements. This is being accomplished by melting and obtaining property data for simulated nuclear waste glasses of various compositions, and then statistically developing models and other tools needed to meet the goal. 6 refs., 1 fig., 5 tabs.

  13. 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.

  14. Identifying contamination with advanced visualization and analysis practices: metagenomic approaches for eukaryotic genome assemblies.

    Science.gov (United States)

    Delmont, Tom O; Eren, A Murat

    2016-01-01

    High-throughput sequencing provides a fast and cost-effective mean to recover genomes of organisms from all domains of life. However, adequate curation of the assembly results against potential contamination of non-target organisms requires advanced bioinformatics approaches and practices. Here, we re-analyzed the sequencing data generated for the tardigrade Hypsibius dujardini, and created a holistic display of the eukaryotic genome assembly using DNA data originating from two groups and eleven sequencing libraries. By using bacterial single-copy genes, k-mer frequencies, and coverage values of scaffolds we could identify and characterize multiple near-complete bacterial genomes from the raw assembly, and curate a 182 Mbp draft genome for H. dujardini supported by RNA-Seq data. Our results indicate that most contaminant scaffolds were assembled from Moleculo long-read libraries, and most of these contaminants have differed between library preparations. Our re-analysis shows that visualization and curation of eukaryotic genome assemblies can benefit from tools designed to address the needs of today's microbiologists, who are constantly challenged by the difficulties associated with the identification of distinct microbial genomes in complex environmental metagenomes.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Heterogeneous Coordination Environments in Lithium-Neutralized Ionomers Identified Using 1H and 7Li MAS NMR

    Directory of Open Access Journals (Sweden)

    Kenneth B. Wagener

    2012-08-01

    Full Text Available The carboxylic acid proton and the lithium coordination environments for precise and random Li-neutralized polyethylene acrylic acid P(E-AA ionomers were explored using high speed solid-state 1H and 7Li MAS NMR. While the 7Li NMR revealed only a single Li coordination environment, the chemical shift temperature variation was dependent on the precise or random nature of the P(E-AA ionomer. The 1H MAS NMR revealed two different carboxylic acid proton environments in these materials. By utilizing 1H-7Li rotational echo double resonance (REDOR MAS NMR experiments, it was demonstrated that the proton environments correspond to different average 1H-7Li distances, with the majority of the protonated carboxylic acids having a close through space contact with the Li. Molecular dynamics simulations suggest that the shortest 1H-7Li distance corresponds to un-neutralized carboxylic acids directly involved in the coordination environment of Li clusters. These solid-state NMR results show that heterogeneous structural motifs need to be included when developing descriptions of these ionomer materials.

  4. 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

  5. Evaluation of different approaches for identifying optimal sites to predict mean hillslope soil moisture content

    Science.gov (United States)

    Liao, Kaihua; Zhou, Zhiwen; Lai, Xiaoming; Zhu, Qing; Feng, Huihui

    2017-04-01

    The identification of representative soil moisture sampling sites is important for the validation of remotely sensed mean soil moisture in a certain area and ground-based soil moisture measurements in catchment or hillslope hydrological studies. Numerous approaches have been developed to identify optimal sites for predicting mean soil moisture. Each method has certain advantages and disadvantages, but they have rarely been evaluated and compared. In our study, surface (0-20 cm) soil moisture data from January 2013 to March 2016 (a total of 43 sampling days) were collected at 77 sampling sites on a mixed land-use (tea and bamboo) hillslope in the hilly area of Taihu Lake Basin, China. A total of 10 methods (temporal stability (TS) analyses based on 2 indices, K-means clustering based on 6 kinds of inputs and 2 random sampling strategies) were evaluated for determining optimal sampling sites for mean soil moisture estimation. They were TS analyses based on the smallest index of temporal stability (ITS, a combination of the mean relative difference and standard deviation of relative difference (SDRD)) and based on the smallest SDRD, K-means clustering based on soil properties and terrain indices (EFs), repeated soil moisture measurements (Theta), EFs plus one-time soil moisture data (EFsTheta), and the principal components derived from EFs (EFs-PCA), Theta (Theta-PCA), and EFsTheta (EFsTheta-PCA), and global and stratified random sampling strategies. Results showed that the TS based on the smallest ITS was better (RMSE = 0.023 m3 m-3) than that based on the smallest SDRD (RMSE = 0.034 m3 m-3). The K-means clustering based on EFsTheta (-PCA) was better (RMSE sampling design stratified by the land use was more efficient than the global random method. Forty and 60 sampling sites are needed for stratified sampling and global sampling respectively to make their performances comparable to the best K-means method (EFsTheta-PCA). Overall, TS required only one site, but its

  6. 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…

  7. A Proteomic Approach to Identify Phosphorylation-Dependent Targets of BRCT Domains

    Science.gov (United States)

    2008-03-01

    targets To develop the BiFC technology for screening for BRCT- BRCA1 interacting proteins in mammalian cells, we constructed expression...domain To screen for BRCA1-BRCT interacting proteins using BiFC, we undertook several approaches. In the last report, we described a reduction approach...candidate BRCT- interacting proteins . Indeed, we obtained many cell clones that exhibited either strong or weak fluorescence, indicating that these

  8. Quantitative and Qualitative Approaches to Identifying Migration Chronology in a Continental Migrant

    OpenAIRE

    Beatty, William S.; Dylan C Kesler; Elisabeth B Webb; Andrew H Raedeke; 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) eq...

  9. Identifying developmental coordination disorder: MOQ-T validity as a fast screening instrument based on teachers' ratings and its relationship with praxic and visuospatial working memory deficits.

    Science.gov (United States)

    Giofrè, David; Cornoldi, Cesare; Schoemaker, Marina M

    2014-12-01

    The present study was devoted to test the validity of the Italian adaptation of the Motor Observation Questionnaire for Teachers (MOQ-T, Schoemaker, Flapper, Reinders-Messelink, & De Kloet, 2008) as a fast screening instrument, based on teachers' ratings, for detecting developmental coordination disorders symptoms and to study its relationship with praxic and visuospatial working memory deficits. In a first study on a large sample of children, we assessed the reliability and structure of the Italian adaptation of the MOQ-T. Results showed a good reliability of the questionnaire and a hierarchical structure with two first-order factors (reflecting motor and handwriting skills), which are influenced by a second-order factor (general motor function) at the top. In a second study, we looked at the external validity of the MOQ-T and found that children with symptoms of Developmental Coordination Disorder (children with high scores on the MOQ-T) also had difficulty reproducing gestures, either imitating others or in response to verbal prompts. Our results also showed that children with high MOQ-T scores had visuospatial WM impairments. The theoretical and clinical implications of these findings are discussed.

  10. Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets

    Directory of Open Access Journals (Sweden)

    Suhas Vasaikar

    2016-11-01

    Full Text Available In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach as one of the factors. Although a number of drugs have been developed with an emphasis on a single protein target, yet identification of valid target is complex. The approach focuses on an in vitro single target, which overlooks the complexity of cell and makes process of validation drug targets uncertain. Thus, it is imperative to search for alternatives rather than looking at success stories of target-based drug discovery. It would be beneficial if the drugs were developed to target multiple components. New approaches like reverse engineering and translational research need to take into account both system and target-based approach. This review evaluates the strengths and limitations of known drug discovery approaches and proposes alternative approaches for increasing efficiency against treatment.

  11. Identifying regime shifts in Indian stock market: A Markov switching approach

    OpenAIRE

    Wasim, Ahmad; Bandi, Kamaiah

    2011-01-01

    Seeking for the existence of bull and bear regimes in the Indian stock market, a two state Markov switching autoregressive model (MS (2)-AR (2)) is used to identify bull and bear market regimes. The model predicts that Indian stock market will remain under bull regime with very high probability compared to bear regime. The results also identify the bear phases during all major global economic crises including recent US sub-prime (2008) and European debt crisis (2010). The paper concludes that...

  12. 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.

  13. 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...... be designed and promoted in order to attract different user groups. This review highlights advances in the understanding of mode choice from a psychological perspective, taking into account behavioural theories of car use and car-use reduction. In this contribution, attitudinal, sociodemographic, geographical...... 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....

  14. 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

    genes with evidence of linkage: ENPP1 (P = 0.003), IGFBP3 (P = 0.006), DHCR7 (P = 0.009), and TRAF2 (P = 0.01). DNA sequence analysis of the coding exons and splice sites for CRHR1 and TRAF2 identified no new likely etiologic variants.Conclusion:These findings suggest the involvement of six genes acting...... used. Premature infants and mothers of premature infants were defined as affected cases in independent analyses.Results:Analyses with the infant as the case identified two genes with evidence of linkage: CRHR1 (P = 0.0012) and CYP2E1 (P = 0.0011). Analyses with the mother as the case identified four...

  15. A Novel Approach to Identifying a Neuroimaging Biomarker for Patients With Serious Mental Illness.

    Science.gov (United States)

    Madan, Alok; Fowler, J Christopher; Patriquin, Michelle A; Salas, Ramiro; Baldwin, Philip R; Velasquez, Kenia M; Viswanath, Humsini; Molfese, David L; Sharp, Carla; Allen, Jon G; Hardesty, Susan; Oldham, John M; Frueh, B Christopher

    2017-02-27

    Serious mental illness (SMI) is disabling, and current interventions are ineffective for many. This exploratory study sought to demonstrate the feasibility of applying topological data analysis (TDA) to resting-state functional connectivity data obtained from a heterogeneous sample of 235 adult inpatients to identify a biomarker of treatment response. TDA identified two groups based on connectivity between the prefrontal cortex and striatal regions: patients admitted with greater functional connectivity between these regions evidenced less improvement from admission to discharge than patients with lesser connectivity between them. TDA identified a potential biomarker of an attenuated treatment response among inpatients with SMI. Insofar as the observed pattern of resting-state functional connectivity collected early during treatment is replicable, this potential biomarker may indicate the need to modify standard of care for a small, albeit meaningful, percentage of patients.

  16. A novel reverse-genetic approach (SIMF) identifies Mutator insertions in new Myb genes.

    Science.gov (United States)

    Rabinowicz, P D; Grotewold, E

    2000-11-01

    We have developed a new strategy designated SIMF (Systematic Insertional Mutagenesis of Families), to identify DNA insertions in many members of a gene family simultaneously. This method requires only a short amino acid sequence conserved in all members of the family to make a degenerate oligonucleotide, and a sequence from the end of the DNA insertion. The SIMF strategy was successfully applied to the large maize R2R3 Myb family of regulatory genes, and Mutator insertions in several novel Myb genes were identified. Application of this technique to identify insertions in other large gene families could significantly decrease the effort involved in screening at the same time for insertions in all members of groups of genes that share a limited sequence identity.

  17. 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.

  18. Numerical and Experimental Approach for Identifying Elastic Parameters in Sandwich Plates

    Directory of Open Access Journals (Sweden)

    Sergio Ferreira Bastos

    2002-01-01

    Full Text Available This article deals with the identification of elastic parameters (engineering constants in sandwich honeycomb orthotropic rectangular plates. A non-destructive method is introduced to identify the elastic parameters through the experimental measurements of natural frequencies of a plate undergoing free vibrations. Four elastic constant are identified. The estimation of the elastic parameter problem is solved by minimizing the differences between the measured and the calculated natural frequencies. The numerical method to calculate the natural frequencies involves the formulation of Rayleigh-Ritz using a series of characteristic orthogonal polynomials to properly model the free edge boundary conditions. The analysis of the results indicates the efficiency of the method.

  19. 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

  20. Constructing New Theory for Identifying Students with Emotional Disturbance: A Grounded Theory Approach

    Science.gov (United States)

    Barnett, Dori A.

    2010-01-01

    The problem area explored by this study is the identification of students with emotional and behavioral difficulties for special education supports and services under the criteria for emotional disturbance (ED). A review of the literature indicated that the problem of identifying students with ED was compounded by subjectivity and ambiguity…

  1. A library screening approach identifies naturally occurring RNA sequences for a G-quadruplex binding ligand.

    Science.gov (United States)

    Mirihana Arachchilage, Gayan; Morris, Mark J; Basu, Soumitra

    2014-02-07

    An RNA G-quadruplex library was synthesised and screened against kanamycin A as the ligand. Naturally occurring G-quadruplex forming sequences that differentially bind to kanamycin A were identified and characterized. This provides a simple and effective strategy for identification of potential intracellular G-quadruplex targets for a ligand.

  2. Enhanced approaches for identifying Amadori products:application to peanut allergens

    Science.gov (United States)

    The dry roasting of peanuts is suggested to influence allergenic sensitization due to formation of advanced glycation end products (AGE) on peanut proteins. Identifying AGEs is technically challenging. The AGE composition of peanut proteins was probed with nanoLC-ESI-MS and MS/MS analyses. Amadori ...

  3. Candidate fire blight resistance genes in Malus identified with the use of genomic tools and approaches

    Science.gov (United States)

    The goal of this research is to utilize current advances in Rosaceae genomics to identify DNA markers for use in marker-assisted selection of durable resistance to fire blight. Candidate fire blight resistance genes were selected and ranked based upon differential expression after inoculation with ...

  4. A complementary bioinformatics approach to identify potential plant cell wall glycosytransferase 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...

  5. 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.

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

    Science.gov (United States)

    2013-04-05

    ... 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 is... discussion at the workshop. As background for the workshop, a literature review document on these...

  7. A DNA barcoding approach to identify plant species in multiflower honey.

    Science.gov (United States)

    Bruni, I; Galimberti, A; Caridi, L; Scaccabarozzi, D; De Mattia, F; Casiraghi, M; Labra, M

    2015-03-01

    The purpose of this study was to test the ability of DNA barcoding to identify the plant origins of processed honey. Four multifloral honeys produced at different sites in a floristically rich area in the northern Italian Alps were examined by using the rbcL and trnH-psbA plastid regions as barcode markers. An extensive reference database of barcode sequences was generated for the local flora to determine the taxonomic composition of honey. Thirty-nine plant species were identified in the four honey samples, each of which originated from a mix of common plants belonging to Castanea, Quercus, Fagus and several herbaceous taxa. Interestingly, at least one endemic plant was found in all four honey samples, providing a clear signature for the geographic identity of these products. DNA of the toxic plant Atropa belladonna was detected in one sample, illustrating the usefulness of DNA barcoding for evaluating the safety of honey.

  8. 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...... gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c). We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion...... of genes potentially involved in T2D....

  9. Comparison of four molecular approaches to identify Candida parapsilosis complex species

    Science.gov (United States)

    Barbedo, Leonardo Silva; Figueiredo-Carvalho, Maria Helena Galdino; Muniz, Mauro de Medeiros; Zancopé-Oliveira, Rosely Maria

    2017-01-01

    Since the description of Candida orthopsilosis and C. metapsilosis in 2005, several methods have been proposed to identify and differentiate these species from C. parapsilosis sensu stricto. Species-specific uniplex polymerase chain reaction (PCR) was performed and compared with sequencing of the D1/D2 region of the LSU 28S rDNA gene, microsatellite typing of C. parapsilosis sensu stricto, and PCR-restriction fragment length polymorphism patterns in the ITS1-5.8S-ITS2 region of the rDNA gene. There was agreement between results of testing of 98 clinical isolates with the four PCR-based methods, with 59 isolates identified as C. parapsilosis sensu stricto, 37 as C. orthopsilosis, and two as C. metapsilosis. PMID:28225905

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

    OpenAIRE

    McElwain Terry F; Cochran Matt H; Bent Stephen J; Bowers Edwin J; Hewitt David G; Ortega-Santos Alfonso; Teel Pete D; Duhaime Roberta A; Ugstad Paul O; Messenger Matthew T; Hillman Robert; Almazán Consuelo; Wagner Gale G; Miller Ryan S; Wikel Stephen K

    2010-01-01

    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,...

  12. 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.

  13. 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.

  14. 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.

  15. A New Approach to Identifying the Most Powerful Gravitational Lensing Telescopes

    CERN Document Server

    Wong, Kenneth C; Ammons, S Mark; Keeton, Charles R; Hogg, David W; Gonzalez, Anthony H

    2013-01-01

    The best gravitational lenses for detecting distant galaxies are those with the largest mass concentrations and the most advantageous configurations of that mass along the line of sight. Our new method for finding such gravitational telescopes uses optical data to identify projected concentrations of luminous red galaxies (LRGs). LRGs are biased tracers of the underlying mass distribution, so lines of sight with the highest total luminosity in LRGs are likely to contain the largest total mass. We apply this selection technique to the Sloan Digital Sky Survey and identify the 200 fields with the highest total LRG luminosities projected within a 3.5' radius over the redshift range 0.1 < z < 0.7. The redshift and angular distributions of LRGs in these fields trace the concentrations of non-LRG galaxies. These fields are diverse; 22.5% contain one known galaxy cluster and 56% contain multiple known clusters previously identified in the literature. Thus, our results confirm that these LRGs trace massive stru...

  16. Coordinating Group report

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    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.

  17. 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

  18. Exome-first approach identified a novel gloss deletion associated with Lowe syndrome.

    Science.gov (United States)

    Watanabe, Miki; Nakagawa, Ryuji; Kohmoto, Tomohiro; Naruto, Takuya; Suga, Ken-Ichi; Goji, Aya; Horikawa, Hideaki; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

    2016-01-01

    Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci.

  19. A competence approach to adult continuing education for identify and classifying living organisms

    Directory of Open Access Journals (Sweden)

    Julio César Rifa Téllez

    2015-09-01

    Full Text Available A competence approach to the systematic identification and classification of vegetal organisms is described in connection with the training of Biology professors for integrating citizens’ attitude to plants, with strictly professional methods. Several theoretical methods were used to construct a general framework together with the application of surveys to experts. The findings include three units of competence together with its components, essential knowledge and performance indicators; patterns of achievement were set in three levels: 1 empirical distinction of the phytodiversity; 2 characterization in the context of wise range use and 3 systematization of systematic botany contents involved in leading the educational process characterized by protagonist strategic actions in management.

  20. Application of a PCR-based approach to identify sex in Hawaiian honeycreepers (Drepanidinae)

    Science.gov (United States)

    Jarvi, S.I.; Banko, P.C.

    2000-01-01

    The application of molecular techniques to conservation genetics issues can provide important guidance criteria for management of endangered species. The results from this study establish that PCR-based approaches for sex determination developed in other bird species (Griffiths and Tiwari 1995; Griffiths et al. 1996, 1998; Ellegren 1996) can be applied with a high degree of confidence to at least four species of Hawaiian honeycreepers. This provides a rapid, reliable method with which population managers can optimize sex ratios within populations of endangered species that are subject to artificial manipulation through captive breeding programmes or geographic translocation.

  1. Identifying "social smoking" U.S. young adults using an empirically-driven approach.

    Science.gov (United States)

    Villanti, Andrea C; Johnson, Amanda L; Rath, Jessica M; Williams, Valerie; Vallone, Donna M; Abrams, David B; Hedeker, Donald; Mermelstein, Robin J

    2017-07-01

    The phenomenon of "social smoking" emerged in the past decade as an important area of research, largely due to its high prevalence in young adults. The purpose of this study was to identify classes of young adult ever smokers based on measures of social and contextual influences on tobacco use. Latent class models were developed using social smoking measures, and not the frequency or quantity of tobacco use. Data come from a national sample of young adult ever smokers aged 18-24 (Truth Initiative Young Adult Cohort Study, N=1564). The optimal models identified three latent classes: Class 1 - nonsmokers (52%); Class 2 - social smokers (18%); and Class 3 - smokers (30%). Nearly 60% of the "social smoker" class self-identified as a social smoker, 30% as an ex-smoker/tried smoking, and 12% as a non-smoker. The "social smoker" class was most likely to report using tobacco mainly or only with others. Past 30-day cigarette use was highest in the "smoker" class. Hookah use was highest in the "social smoker" class. Other tobacco and e-cigarette use was similar in the "social smoker" and "smoker" classes. Past 30-day tobacco and e-cigarette use was present for all products in the "non-smoker" class. Young adult social smokers emerge empirically as a sizable, distinct class from other smokers, even without accounting for tobacco use frequency or intensity. The prevalence of hookah use in "social smokers" indicates a group for which the social aspect of tobacco use could drive experimentation and progression to regular use.

  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. A Data Mining Approach to Identify Sexuality Patterns in a Brazilian University Population.

    Science.gov (United States)

    Waleska Simões, Priscyla; Cesconetto, Samuel; Toniazzo de Abreu, Larissa Letieli; Côrtes de Mattos Garcia, Merisandra; Cassettari Junior, José Márcio; Comunello, Eros; Bisognin Ceretta, Luciane; Aparecida Manenti, Sandra

    2015-01-01

    This paper presents the profile and experience of sexuality generated from a data mining classification task. We used a database about sexuality and gender violence performed on a university population in southern Brazil. The data mining task identified two relationships between the variables, which enabled the distinction of subgroups that better detail the profile and experience of sexuality. The identification of the relationships between the variables define behavioral models and factors of risk that will help define the algorithms being implemented in the data mining classification task.

  5. 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

  6. A phenotypic screening approach to identify anticancer compounds derived from marine fungi.

    Science.gov (United States)

    Ellinger, Bernhard; Silber, Johanna; Prashar, Anjali; Landskron, Johannes; Weber, Jonas; Rehermann, Sarah; Müller, Franz-Josef; Smith, Stephen; Wrigley, Stephen; Taskén, Kjetil; Gribbon, Philip; Labes, Antje; Imhoff, Johannes F

    2014-04-01

    This study covers the isolation, testing, and identification of natural products with anticancer properties. Secondary metabolites were isolated from fungal strains originating from a variety of marine habitats. Strain culture protocols were optimized with respect to growth media composition and fermentation conditions. From these producers, isolated compounds were screened for their effect on the viability and proliferation of a subset of the NCI60 panel of cancer cell lines. Active compounds of interest were identified and selected for detailed assessments and structural elucidation using nuclear magnetic resonance. This revealed the majority of fungal-derived compounds represented known anticancer chemotypes, confirming the integrity of the process and the ability to identify suitable compounds. Examination of effects of selected compounds on cancer-associated cell signaling pathways used phospho flow cytometry in combination with 3D fluorescent cell barcoding. In parallel, the study addressed the logistical aspects of maintaining multiple cancer cell lines in culture simultaneously. A potential solution involving microbead-based cell culture was investigated (BioLevitator, Hamilton). Selected cell lines were cultured in microbead and 2D methods and cell viability tests showed comparable compound inhibition in both methods (R2=0.95). In a further technology assessment, an image-based assay system was investigated for its utility as a possible complement to ATP-based detection for quantifying cell growth and viability in a label-free manner.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Chang eShen

    2016-02-01

    Full Text Available 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 and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association studies (GWASs. More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWASs. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo, such as immunoregulatory function, melanocyte regulation and so on. A number of 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 vitiligo development.

  10. Team coordination dynamics.

    Science.gov (United States)

    Gorman, Jamie C; Amazeen, Polemnia G; Cooke, Nancy J

    2010-07-01

    Team coordination consists of both the dynamics of team member interaction and the environmental dynamics to which a team is subjected. Focusing on dynamics, an approach is developed that contrasts with traditional aggregate-static concepts of team coordination as characterized by the shared mental model approach. A team coordination order parameter was developed to capture momentary fluctuations in coordination. Team coordination was observed in three-person uninhabited air vehicle teams across two experimental sessions. The dynamics of the order parameter were observed under changes of a team familiarity control parameter. Team members returned for the second session to either the same (Intact) or different (Mixed) team. 'Roadblock' perturbations, or novel changes in the task environment, were introduced in order to probe the stability of team coordination. Nonlinear dynamic methods revealed differences that a traditional approach did not: Intact and Mixed team coordination dynamics looked very different; Mixed teams were more stable than Intact teams and explored the space of solutions without the need for correction. Stability was positively correlated with the number of roadblock perturbations that were overcome successfully. The novel and non-intuitive contribution of a dynamical analysis was that Mixed teams, who did not have a long history working together, were more adaptive. Team coordination dynamics carries new implications for traditional problems such as training adaptive teams.

  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. Utilizing Soize's Approach to Identify Parameter and Model Uncertainties

    Energy Technology Data Exchange (ETDEWEB)

    Bonney, Matthew S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Univ. of Wisconsin, Madison, WI (United States); Brake, Matthew Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-10-01

    Quantifying uncertainty in model parameters is a challenging task for analysts. Soize has derived a method that is able to characterize both model and parameter uncertainty independently. This method is explained with the assumption that some experimental data is available, and is divided into seven steps. Monte Carlo analyses are performed to select the optimal dispersion variable to match the experimental data. Along with the nominal approach, an alternative distribution can be used along with corrections that can be utilized to expand the scope of this method. This method is one of a very few methods that can quantify uncertainty in the model form independently of the input parameters. Two examples are provided to illustrate the methodology, and example code is provided in the Appendix.

  13. 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....

  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. 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.

  16. 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

  17. Ovarian serous adenocarcinoma identified during IVF: diagnostic approach, surgical management, and reproductive outcome

    Directory of Open Access Journals (Sweden)

    Gleeson Noreen C

    2009-05-01

    Full Text Available Abstract Background To present a diagnostic evaluation and treatment strategy for serous adenocarcinoma of the ovary discovered during an in vitro fertilisation (IVF sequence, and report on reproductive outcome after tumour resection and embryo transfer. Case presentation Cycle monitoring in IVF identified an abnormal ovarian lesion which was subjected to ultrasound-guided needle aspiration. Cytology suggested malignancy, and unilateral oophorectomy was performed after formal staging. After surgery, the patient underwent an anonymous donor oocyte IVF cycle which established a viable twin intrauterine pregnancy. No recurrence of cancer has been detected in the >72 month follow-up interval; mother and twin daughters continue to do well. Conclusion Suspicious adnexal structures noted during controlled ovarian hyperstimulation for IVF warrant assessment, and this report confirms the role of aspiration cytology in such cases. If uterine conservation is possible, successful livebirth can be achieved from IVF if donor oocyes are utilised, as described here.

  18. Molecular approaches to identify cryptic species and polymorphic species within a complex community of fig wasps.

    Directory of Open Access Journals (Sweden)

    Jin-Hua Xiao

    Full Text Available Cryptic and polymorphic species can complicate traditional taxonomic research and both of these concerns are common in fig wasp communities. Species identification is very difficult, despite great effort and the ecological importance of fig wasps. Herein, we try to identify all chalcidoid wasp species hosted by one species of fig, using both morphological and molecular methods. We compare the efficiency of four different DNA regions and find that ITS2 is highly effective for species identification, while mitochondrial COI and Cytb regions appear less reliable, possibly due to the interference signals from either nuclear copies of mtDNA, i.e. NUMTs, or the effects of Wolbachia infections. The analyses suggest that combining multiple markers is the best choice for inferring species identifications as any one marker may be unsuitable in a given case.

  19. A high-throughput approach to identify compounds that impair envelope integrity in Escherichia coli

    DEFF Research Database (Denmark)

    Baker, Kristin Renee; Jana, Bimal; Franzyk, Henrik

    2016-01-01

    was to develop and validate an assay for identifying compounds that increase envelope permeability, thereby conferring antimicrobial susceptibility by weakening of the cell envelope barrier in Gram-negative bacteria. A high-throughput whole-cell screening platform was developed to measure Escherichia coli...... sequence type 131 clone. Notably, in the presence of 0.25 μM of this peptide, both strains were susceptible to rifampin according to the resistance breakpoints (R > 0.5 μg/ml) for Gram-positive bacterial pathogens. The high-throughput screening platform developed in this study can be applied to accelerate...... the discovery of antimicrobial helper drug candidates and targets that enhance the delivery of existing antibiotics by impairing envelope integrity in Gram-negative bacteria....

  20. A new system identification approach to identify genetic variants in sequencing studies for a binary phenotype.

    Science.gov (United States)

    Kang, Guolian; Bi, Wenjian; Zhao, Yanlong; Zhang, Ji-Feng; Yang, Jun J; Xu, Heng; Loh, Mignon L; Hunger, Stephen P; Relling, Mary V; Pounds, Stanley; Cheng, Cheng

    2014-01-01

    We propose in this paper a set-valued (SV) system model, which is a generalized form of logistic (LG) and Probit (Probit) regression, to be considered as a method for discovering genetic variants, especially rare genetic variants in next-generation sequencing studies, for a binary phenotype. We propose a new SV system identification method to estimate all underlying key system parameters for the Probit model and compare it with the LG model in the setting of genetic association studies. Across an extensive series of simulation studies, the Probit method maintained type I error control and had similar or greater power than the LG method, which is robust to different distributions of noise: logistic, normal, or t distributions. Additionally, the Probit association parameter estimate was 2.7-46.8-fold less variable than the LG log-odds ratio association parameter estimate. Less variability in the association parameter estimate translates to greater power and robustness across the spectrum of minor allele frequencies (MAFs), and these advantages are the most pronounced for rare variants. For instance, in a simulation that generated data from an additive logistic model with an odds ratio of 7.4 for a rare single nucleotide polymorphism with a MAF of 0.005 and a sample size of 2,300, the Probit method had 60% power whereas the LG method had 25% power at the α = 10(-6) level. Consistent with these simulation results, the set of variants identified by the LG method was a subset of those identified by the Probit method in two example analyses. Thus, we suggest the Probit method may be a competitive alternative to the LG method in genetic association studies such as candidate gene, genome-wide, or next-generation sequencing studies for a binary phenotype.

  1. PREDICT‐PD: An online approach to prospectively identify risk indicators of Parkinson's disease

    Science.gov (United States)

    Noyce, Alastair J.; R'Bibo, Lea; Peress, Luisa; Bestwick, Jonathan P.; Adams‐Carr, Kerala L.; Mencacci, Niccolo E.; Hawkes, Christopher H.; Masters, Joseph M.; Wood, Nicholas; Hardy, John; Giovannoni, Gavin; Lees, Andrew J.

    2017-01-01

    Background A number of early features can precede the diagnosis of Parkinson's disease (PD). Objective To test an online, evidence‐based algorithm to identify risk indicators of PD in the UK population. Methods Participants aged 60 to 80 years without PD completed an online survey and keyboard‐tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine‐rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD (“intermediate markers”), including smell loss, rapid eye movement–sleep behavior disorder, and finger‐tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed. Results A total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow‐up (all P values power for incident PD was improved by the addition of genetic variants to risk scores. Conclusions The online PREDICT‐PD algorithm is a unique and simple method to identify indicators of PD risk. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:28090684

  2. A New System Identification Approach to Identifying Genetic Variants in Sequencing Studies for A Binary Phenotype

    Science.gov (United States)

    Kang, Guolian; Bi, Wenjian; Zhao, Yanlong; Zhang, Ji-Feng; Yang, Jun J.; Xu, Heng; Loh, Mignon L.; Hunger, Stephen P.; Relling, Mary V.; Pounds, Stanley; Cheng, Cheng

    2014-01-01

    We propose in this paper a set-valued (SV) system model, which is a generalized form of Logistic (LG) and Probit (Probit) regression, to be considered as a method for discovering genetic variants, especially rare genetic variants in next generation sequencing studies, for a binary phenotype. We propose a new set-valued system identification method to estimate all the underlying key system parameters for the Probit model and compare it with the LG model in the setting of genetic association studies. Across an extensive series of simulation studies, the Probit method maintained Type I error control and had similar or greater power than the LG method which is robust to different distributions of noise: logistic, normal or t distributions. Additionally, the Probit association parameter estimate was 2.7–46.8 fold less variable than the LG log-odds ratio association parameter estimate. Less variability in the association parameter estimate translates to greater power and robustness across the spectrum of minor allele frequencies (MAFs), and these advantages are the most pronounced for rare variants. For instance, in a simulation that generated data from an additive logistic model with odds ratio of 7.4 for a rare single nucleotide polymorphism with a MAF of 0.005 and a sample size of 2300, the Probit method had 60% power whereas the LG method had 25% power at the α=10−6 level. Consistent with these simulation results, the set of variants identified by the LG method was a subset of those identified by the Probit method in two example analyses. Thus, we suggest the Probit method may be a competitive alternative to the LG method in genetic association studies such as candidate gene, genome-wide, or next generation sequencing studies for a binary phenotype. PMID:25096228

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

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

    Science.gov (United States)

    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 monoterpene pathway under low ambient-light intensities, which led to an accumulation of the branchpoint intermediate (+)-pulegone and the side product (+)-menthofuran. Our simulations indicated that the environmentally regulated changes in monoterpene profiles could only be explained when, in addition to effects on biosynthetic enzyme activities, as yet unidentified inhibitory effects of (+)-menthofuran on the branchpoint enzyme pulegone reductase (PR) were assumed. Subsequent in vitro analyses with recombinant protein confirmed that (+)-menthofuran acts as a weak competitive inhibitor of PR (Ki = 300 μM). To evaluate whether the intracellular concentration of (+)-menthofuran was high enough for PR inhibition in vivo, we isolated essential oil-synthesizing secretory cells from peppermint leaves and subjected them to steam distillations. When peppermint plants were grown under low-light conditions, (+)-menthofuran was selectively retained in secretory cells and accumulated to very high levels (up to 20 mM), whereas under regular growth conditions, (+)-menthofuran levels remained very low (<400 μM). These results illustrate the utility of iterative cycles of mathematical modeling and experimental testing to elucidate the mechanisms controlling flux through metabolic pathways. PMID:18287058

  10. An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates.

    Science.gov (United States)

    Hawley, Robert G; Chen, Yuzhong; Riz, Irene; Zeng, Chen

    2012-05-04

    In this study, we utilized an integrated bioinformatics and computational biology approach in search of new BH3-only proteins belonging to the BCL2 family of apoptotic regulators. The BH3 (BCL2 homology 3) domain mediates specific binding interactions among various BCL2 family members. It is composed of an amphipathic α-helical region of approximately 13 residues that has only a few amino acids that are highly conserved across all members. Using a generalized motif, we performed a genome-wide search for novel BH3-containing proteins in the NCBI Consensus Coding Sequence (CCDS) database. In addition to known pro-apoptotic BH3-only proteins, 197 proteins were recovered that satisfied the search criteria. These were categorized according to α-helical content and predictive binding to BCL-xL (encoded by BCL2L1) and MCL-1, two representative anti-apoptotic BCL2 family members, using position-specific scoring matrix models. Notably, the list is enriched for proteins associated with autophagy as well as a broad spectrum of cellular stress responses such as endoplasmic reticulum stress, oxidative stress, antiviral defense, and the DNA damage response. Several potential novel BH3-containing proteins are highlighted. In particular, the analysis strongly suggests that the apoptosis inhibitor and DNA damage response regulator, AVEN, which was originally isolated as a BCL-xL-interacting protein, is a functional BH3-only protein representing a distinct subclass of BCL2 family members.

  11. 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.

  12. 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.

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

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    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.

  14. Identifying overrepresented concepts in gene lists from literature: a statistical approach based on Poisson mixture model

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    Zhai Chengxiang

    2010-05-01

    Full Text Available Abstract Background Large-scale genomic studies often identify large gene lists, for example, the genes sharing the same expression patterns. The interpretation of these gene lists is generally achieved by extracting concepts overrepresented in the gene lists. This analysis often depends on manual annotation of genes based on controlled vocabularies, in particular, Gene Ontology (GO. However, the annotation of genes is a labor-intensive process; and the vocabularies are generally incomplete, leaving some important biological domains inadequately covered. Results We propose a statistical method that uses the primary literature, i.e. free-text, as the source to perform overrepresentation analysis. The method is based on a statistical framework of mixture model and addresses the methodological flaws in several existing programs. We implemented this method within a literature mining system, BeeSpace, taking advantage of its analysis environment and added features that facilitate the interactive analysis of gene sets. Through experimentation with several datasets, we showed that our program can effectively summarize the important conceptual themes of large gene sets, even when traditional GO-based analysis does not yield informative results. Conclusions We conclude that the current work will provide biologists with a tool that effectively complements the existing ones for overrepresentation analysis from genomic experiments. Our program, Genelist Analyzer, is freely available at: http://workerbee.igb.uiuc.edu:8080/BeeSpace/Search.jsp

  15. 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.

  16. 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.

  17. 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

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

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    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

  19. 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.

  20. 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.

  1. 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.

  2. Ab initio Thermodynamic Approach to Identify Mixed Solid Sorbents for CO2 Capture Technology

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    Yuhua eDuan

    2015-10-01

    Full Text Available Because the current technologies for capturing CO2 are still too energy intensive, new materials must be developed that can capture CO2 reversibly with acceptable energy costs. At a given CO2 pressure, the turnover temperature (Tt of the reaction of an individual solid that can capture CO2 is fixed. Such Tt may be outside the operating temperature range (ΔTo for a practical capture technology. To adjust Tt to fit the practical ΔTo, in this study, three scenarios of mixing schemes are explored by combining thermodynamic database mining with first principles density functional theory and phonon lattice dynamics calculations. Our calculated results demonstrate that by mixing different types of solids, it’s possible to shift Tt to the range of practical operating temperature conditions. According to the requirements imposed by the pre- and post- combustion technologies and based on our calculated thermodynamic properties for the CO2 capture reactions by the mixed solids of interest, we were able to identify the mixing ratios of two or more solids to form new sorbent materials for which lower capture energy costs are expected at the desired pressure and temperature conditions.

  3. 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.

  4. 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.

  5. A zone-based approach to identifying urban land uses using nationally-available data

    Science.gov (United States)

    Falcone, James A.

    Accurate identification of urban land use is essential for many applications in environmental study, ecological assessment, and urban planning, among other fields. However, because physical surfaces of land cover types are not necessarily related to their use and economic function, differentiating among thematically-detailed urban land uses (single-family residential, multi-family residential, commercial, industrial, etc.) using remotely-sensed imagery is a challenging task, particularly over large areas. Because the process requires an interpretation of tone/color, size, shape, pattern, and neighborhood association elements within a scene, it has traditionally been accomplished via manual interpretation of aerial photography or high-resolution satellite imagery. Although success has been achieved for localized areas using various automated techniques based on high-spatial or high-spectral resolution data, few detailed (Anderson Level II equivalent or greater) urban land use mapping products have successfully been created via automated means for broad (multi-county or larger) areas, and no such product exists today for the United States. In this study I argue that by employing a zone-based approach it is feasible to map thematically-detailed urban land use classes over large areas using appropriate combinations of non-image based predictor data which are nationally and publicly available. The approach presented here uses U.S. Census block groups as the basic unit of geography, and predicts the percent of each of ten land use types---nine of them urban---for each block group based on a number of data sources, to include census data, nationally-available point locations of features from the USGS Geographic Names Information System, historical land cover, and metrics which characterize spatial pattern, context (e.g. distance to city centers or other features), and measures of spatial autocorrelation. The method was demonstrated over a four-county area surrounding the

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

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    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. Repurposing Approach Identifies Auranofin with Broad Spectrum Antifungal Activity That Targets Mia40-Erv1 Pathway

    Science.gov (United States)

    Thangamani, Shankar; Maland, Matthew; Mohammad, Haroon; Pascuzzi, Pete E.; Avramova, Larisa; Koehler, Carla M.; Hazbun, Tony R.; Seleem, Mohamed N.

    2017-01-01

    Current antifungal therapies have limited effectiveness in treating invasive fungal infections. Furthermore, the development of new antifungal is currently unable to keep pace with the urgent demand for safe and effective new drugs. Auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, inhibits growth of a diverse array of clinical isolates of fungi and represents a new antifungal agent with a previously unexploited mechanism of action. In addition to auranofin's potent antifungal activity against planktonic fungi, this drug significantly reduces the metabolic activity of Candida cells encased in a biofilm. Unbiased chemogenomic profiling, using heterozygous S. cerevisiae deletion strains, combined with growth assays revealed three probable targets for auranofin's antifungal activity—mia40, acn9, and coa4. Mia40 is of particular interest given its essential role in oxidation of cysteine rich proteins imported into the mitochondria. Biochemical analysis confirmed auranofin targets the Mia40-Erv1 pathway as the drug inhibited Mia40 from interacting with its substrate, Cmc1, in a dose-dependent manner similar to the control, MB-7. Furthermore, yeast mitochondria overexpressing Erv1 were shown to exhibit resistance to auranofin as an increase in Cmc1 import was observed compared to wild-type yeast. Further in vivo antifungal activity of auranofin was examined in a Caenorhabditis elegans animal model of Cryptococcus neoformans infection. Auranofin significantly reduced the fungal load in infected C. elegans. Collectively, the present study provides valuable evidence that auranofin has significant promise to be repurposed as a novel antifungal agent and may offer a safe, effective, and quick supplement to current approaches for treating fungal infections. PMID:28149831

  8. 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

  9. Identifying Opportunities for Decision Support Systems in Support of Regional Resource Use Planning: An Approach Through Soft Systems Methodology.

    Science.gov (United States)

    Zhu; Dale

    2000-10-01

    / Regional resource use planning relies on key regional stakeholder groups using and having equitable access to appropriate social, economic, and environmental information and assessment tools. Decision support systems (DSS) can improve stakeholder access to such information and analysis tools. Regional resource use planning, however, is a complex process involving multiple issues, multiple assessment criteria, multiple stakeholders, and multiple values. There is a need for an approach to DSS development that can assist in understanding and modeling complex problem situations in regional resource use so that areas where DSSs could provide effective support can be identified, and the user requirements can be well established. This paper presents an approach based on the soft systems methodology for identifying DSS opportunities for regional resource use planning, taking the Central Highlands Region of Queensland, Australia, as a case study.

  10. Integrative approach to pain genetics identifies pain sensitivity loci across diseases.

    Directory of Open Access Journals (Sweden)

    David Ruau

    Full Text Available Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI, derived from Medical Subject Heading (MESH annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10⁻¹⁰ for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10⁻⁴, 1.8×10⁻⁴, and 2.2×10⁻⁴ respectively. Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates.

  11. 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.

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

    OpenAIRE

    Adelstein S James; Iyer Lakshmanan K; Pospisil Pavel; Kassis Amin I

    2006-01-01

    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. Pr...

  13. 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

  14. A systems biology approach to identify the signalling network regulated by Rho-GDI-γ during neural stem cell differentiation.

    Science.gov (United States)

    Wang, Jiao; Hu, Fuyan; Cheng, Hua; Zhao, Xing-Ming; Wen, Tieqiao

    2012-11-01

    Understanding the molecular mechanism that underlies the differentiation of neural stem cells (NSCs) is vital to develop regenerative medicines for neurological disorders. In our previous work, Rho-GDI-γ was found to be able to prompt neuronal differentiation when it was down regulated. However, it is unclear how Rho-GDI-γ regulates this differentiation process. Therefore, a novel systems biology approach is presented here to identify putative signalling pathways regulated by Rho-GDI-γ during NSC differentiation, and these pathways can provide insights into the NSC differentiation mechanisms. In particular, our proposed approach combines the predictive power of computational biology and molecular experiments. With different biological experiments, the genes in the computationally identified signalling network were validated to be indeed regulated by Rho-GDI-γ during the differentiation of NSCs. In particular, one randomly selected pathway involving Vcp, Mapk8, Ywhae and Ywhah was experimentally verified to be regulated by Rho-GDI-γ. These promising results demonstrate the effectiveness of our proposed systems biology approach, indicating the potential predictive power of integrating computational and experimental approaches.

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

    Science.gov (United States)

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

    2013-08-01

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

  16. The stochastic separatrix and the reaction coordinate for complex systems.

    Science.gov (United States)

    Antoniou, Dimitri; Schwartz, Steven D

    2009-04-21

    We present a new approach to the identification of degrees of freedom which comprise a reaction coordinate in a complex system. The method begins with the generation of an ensemble of reactive trajectories. Each trajectory is analyzed for its equicommittor position or transition state; then the transition state ensemble is identified as the stochastic separatrix. Numerical analysis of the points along the separatrix for variability of coordinate location correctly identifies the components of the reaction coordinate in a test system of a double well coupled to a promoting vibration and a bath of linearly coupled oscillators.

  17. OBJECT-ORIENTED APPROACH TO IDENTIFYING THE RELEVANCE OF IT-EDUCATION TO THE LABOR MARKET DEMAND

    Directory of Open Access Journals (Sweden)

    Masuma H. Mamedova

    2014-01-01

    Full Text Available The paper deals with the issues of human resources development and IT-staff training. The authors put a special emphasis on bringing the IT-staff training system in line with the labor market demands both in quantitative and qualitative terms. Based on the object-oriented approach, the authors explore the reasons behind the existing imbalance between the markets of IT-education services and IT-specialists in Azerbaijan, the challenges facing the IT education and specificity of the IT-specialists market being described.For overcoming the above gap between the IT labor market supply and demand, the authors put forward a model of professional competences, reflecting the real-life requirements for a specialist’s quality. Additionally, the paper outlines the recommended trends of IT-sector development in Azerbaijan, which include organization of innovative research and education centers for specialists’ training and retraining, legislative and institutional coordination of the IT industry and education, development of new educational standards, increase in the number of IT-profile students.

  18. 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.

  19. 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.

  20. Who’s Who at the Border? A rights-based approach to identifying human trafficking at international borders

    Directory of Open Access Journals (Sweden)

    Marika McAdam

    2013-11-01

    Full Text Available International borders are widely touted as bastions in the fight against trafficking in persons. This article acknowledges the important role border officials play in preventing human trafficking, but calls for expectations to be tempered by deference to the conceptual complexity of cross-border trafficking and the migration processes involved. The fact that many trafficked victims begin their journeys as irregular or smuggled migrants highlights the challenge posed to border officials in identifying trafficked persons among the people they encounter. Indicators of trafficking generally relate to the exploitation phase, leaving border officials with little guidance as to how persons vulnerable to trafficking can be accurately identified before any exploitation has occurred. Ultimately, this paper advocates a pragmatic rights-based approach in designating anti-trafficking functions to border officials. A rights-based approach to border control acknowledges the core work of border officials as being to uphold border integrity, while ensuring that their performance of this role does not jeopardise the rights of those they intercept nor result in missed opportunities for specialists to identify trafficked persons and other vulnerable people among them.

  1. 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

  2. Five-coordinated oxovanadium(IV) complexes derived from amino acids and ciprofloxacin: synthesis, spectral, antimicrobial, and DNA interaction approach.

    Science.gov (United States)

    Patel, M N; Patel, S H; Chhasatia, M R; Parmar, P A

    2008-12-15

    Five-coordinated oxovanadium(IV) complexes with ciprofloxacin and various uninegative bidentate amino acids have been prepared. The structure of complexes has been investigated using spectral, physicochemical, mass spectroscopy, and elemental analyses. The antimicrobial activities (MIC) of the complexes, ligands, metal salt, and some standard drugs have been evaluated using the doubling dilution technique against Staphylococcus aureus, Bacillus subtilis, Serratia marcescens (gram-positive), and Pseudomonas aeruginosa, and Escherichia coli (gram-negative) bacteria. The result shows the significant increase in the antibacterial activity of the ligand, metal, and ciprofloxacin on complexation. The interaction of the complexes with pBR322 DNA has been investigated using spectroscopic, gel electrophoresis, and viscometric techniques. This shows that the complexes can bind to pBR322 DNA by the intercalative mode. The superoxide dismutase-like activity of the complexes has been determined.

  3. Sonochemical synthesis of two new nano lead(II) coordination polymers: Evaluation of structural transformation via mechanochemical approach.

    Science.gov (United States)

    Aboutorabi, Leila; Morsali, Ali

    2016-09-01

    Two new lead(II) mixed-ligand coordination polymers, [Pb(PNO)(SCN)]n (1) and [Pb(PNO)(N3)]n (2), (HPNO=picolinic acid N-oxide) were synthesized by a sonochemical method and characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analysis. Compounds 1 and 2 were structurally characterized by single crystal X-ray diffraction. The thermal behavior of 1 and 2 were studied by thermal gravimetric analysis. Structural transformations of compounds 1 and 2 were evaluated through anion-replacement processes by mechanochemical method. Moreover, the effect of sonication conditions including time, concentrations of initial reagents and power of irradiation were evaluated on size and morphology of compounds 1 and 2.

  4. 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

    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...... 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...... in their reviews. Through a regression analysis on numerical employee satisfaction ratings, we find that a culture of learning and performance orientation contributes to employee motivation, while a culture of assertiveness and gender inegalitarianism has a strong negative influence on employees’ satisfaction...

  5. 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

  6. CONDITIONAL PROBABILITY ANALYSIS APPROACH FOR IDENTIFYING BIOLOGICAL THRESHOLD OF IMPACT FOR SEDIMENTATION: APPICATION TO FRESHWATER STREAMS IN OREGON COAST RANGE ECOREGION

    Science.gov (United States)

    A conditional probability analysis (CPA) approach has been developed for identifying biological thresholds of impact for use in the development of geographic-specific water quality criteria for protection of aquatic life. This approach expresses the threshold as the likelihood ...

  7. Integrated pathway-based approach identifies association between genomic regions at CTCF and CACNB2 and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Dilafruz Juraeva

    2014-06-01

    Full Text Available In the present study, an integrated hierarchical approach was applied to: (1 identify pathways associated with susceptibility to schizophrenia; (2 detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3 annotate the functional consequences of such single-nucleotide polymorphisms (SNPs in the affected genes or their regulatory regions. The Global Test was applied to detect schizophrenia-associated pathways using discovery and replication datasets comprising 5,040 and 5,082 individuals of European ancestry, respectively. Information concerning functional gene-sets was retrieved from the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and the Molecular Signatures Database. Fourteen of the gene-sets or pathways identified in the discovery dataset were confirmed in the replication dataset. These include functional processes involved in transcriptional regulation and gene expression, synapse organization, cell adhesion, and apoptosis. For two genes, i.e. CTCF and CACNB2, evidence for association with schizophrenia was available (at the gene-level in both the discovery study and published data from the Psychiatric Genomics Consortium schizophrenia study. Furthermore, these genes mapped to four of the 14 presently identified pathways. Several of the SNPs assigned to CTCF and CACNB2 have potential functional consequences, and a gene in close proximity to CACNB2, i.e. ARL5B, was identified as a potential gene of interest. Application of the present hierarchical approach thus allowed: (1 identification of novel biological gene-sets or pathways with potential involvement in the etiology of schizophrenia, as well as replication of these findings in an independent cohort; (2 detection of genes of interest for future follow-up studies; and (3 the highlighting of novel genes in previously reported candidate regions for schizophrenia.

  8. 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.

  9. 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.

  10. SMpred: a support vector machine approach to identify structural motifs in protein structure without using evolutionary information.

    Science.gov (United States)

    Pugalenthi, Ganesan; Kandaswamy, Krishna Kumar; Suganthan, P N; Sowdhamini, R; Martinetz, Thomas; Kolatkar, Prasanna R

    2010-12-01

    Knowledge of three dimensional structure is essential to understand the function of a protein. Although the overall fold is made from the whole details of its sequence, a small group of residues, often called as structural motifs, play a crucial role in determining the protein fold and its stability. Identification of such structural motifs requires sufficient number of sequence and structural homologs to define conservation and evolutionary information. Unfortunately, there are many structures in the protein structure databases have no homologous structures or sequences. In this work, we report an SVM method, SMpred, to identify structural motifs from single protein structure without using sequence and structural homologs. SMpred method was trained and tested using 132 proteins domains containing 581 motifs. SMpred method achieved 78.79% accuracy with 79.06% sensitivity and 78.53% specificity. The performance of SMpred was evaluated with MegaMotifBase using 188 proteins containing 1161 motifs. Out of 1161 motifs, SMpred correctly identified 1503 structural motifs reported in MegaMotifBase. Further, we showed that SMpred is useful approach for the length deviant superfamilies and single member superfamilies. This result suggests the usefulness of our approach for facilitating the identification of structural motifs in protein structure in the absence of sequence and structural homologs. The dataset and executable for the SMpred algorithm is available at http://www3.ntu.edu.sg/home/EPNSugan/index_files/SMpred.htm.

  11. Chemical genetic approach identifies microtubule affinity-regulating kinase 1 as a leucine-rich repeat kinase 2 substrate.

    Science.gov (United States)

    Krumova, Petranka; Reyniers, Lauran; Meyer, Marc; Lobbestael, Evy; Stauffer, Daniela; Gerrits, Bertran; Muller, Lionel; Hoving, Sjouke; Kaupmann, Klemens; Voshol, Johannes; Fabbro, Doriano; Bauer, Andreas; Rovelli, Giorgio; Taymans, Jean-Marc; Bouwmeester, Tewis; Baekelandt, Veerle

    2015-07-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of autosomal-dominant forms of Parkinson's disease. LRRK2 is a modular, multidomain protein containing 2 enzymatic domains, including a kinase domain, as well as several protein-protein interaction domains, pointing to a role in cellular signaling. Although enormous efforts have been made, the exact pathophysiologic mechanisms of LRRK2 are still not completely known. In this study, we used a chemical genetics approach to identify LRRK2 substrates from mouse brain. This approach allows the identification of substrates of 1 particular kinase in a complex cellular environment. Several of the identified peptides are involved in the regulation of microtubule (MT) dynamics, including microtubule-associating protein (MAP)/microtubule affinity-regulating kinase 1 (MARK1). MARK1 is a serine/threonine kinase known to phosphorylate MT-binding proteins such as Tau, MAP2, and MAP4 at KXGS motifs leading to MT destabilization. In vitro kinase assays and metabolic-labeling experiments in living cells confirmed MARK1 as an LRRK2 substrate. Moreover, we also showed that LRRK2 and MARK1 are interacting in eukaryotic cells. Our findings contribute to the identification of physiologic LRRK2 substrates and point to a potential mechanism explaining the reported effects of LRRK2 on neurite morphology.

  12. Disease-Specific Regions Outperform Whole-Brain Approaches in Identifying Progressive Supranuclear Palsy: A Multicentric MRI Study

    Science.gov (United States)

    Mueller, Karsten; Jech, Robert; Bonnet, Cecilia; Tintěra, Jaroslav; Hanuška, Jaromir; Möller, Harald E.; Fassbender, Klaus; Ludolph, Albert; Kassubek, Jan; Otto, Markus; Růžička, Evžen; Schroeter, Matthias L.

    2017-01-01

    To identify progressive supranuclear palsy (PSP), we combined voxel-based morphometry (VBM) and support vector machine (SVM) classification using disease-specific features in multicentric magnetic resonance imaging (MRI) data. Structural brain differences were investigated at four centers between 20 patients with PSP and 20 age-matched healthy controls with T1-weighted MRI at 3T. To pave the way for future application in personalized medicine, we applied SVM classification to identify PSP on an individual level besides group analyses based on VBM. We found a major decline in gray matter density in the brainstem, insula, and striatum, and also in frontomedian regions, which is in line with current literature. Moreover, SVM classification yielded high accuracy rates above 80% for disease identification in imaging data. Focusing analyses on disease-specific regions-of-interest (ROI) led to higher accuracy rates compared to a whole-brain approach. Using a polynomial kernel (instead of a linear kernel) led to an increased sensitivity and a higher specificity of disease detection. Our study supports the application of MRI for individual diagnosis of PSP, if combined with SVM approaches. We demonstrate that SVM classification provides high accuracy rates in multicentric data—a prerequisite for potential application in diagnostic routine. PMID:28326008

  13. The density matrix functional approach to electron correlation: Dynamic and nondynamic correlation along the full dissociation coordinate

    Energy Technology Data Exchange (ETDEWEB)

    Mentel, Ł. M.; Meer, R. van; Gritsenko, O. V. [Section Theoretical Chemistry, VU University, Amsterdam (Netherlands); Pohang University of Science and Technology, Pohang (Korea, Republic of); Baerends, E. J. [Section Theoretical Chemistry, VU University, Amsterdam (Netherlands); Pohang University of Science and Technology, Pohang (Korea, Republic of); Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia)

    2014-06-07

    For chemistry an accurate description of bond weakening and breaking is vital. The great advantage of density matrix functionals, as opposed to density functionals, is their ability to describe such processes since they naturally cover both nondynamical and dynamical correlation. This is obvious in the Löwdin-Shull functional, the exact natural orbital functional for two-electron systems. We present in this paper extensions of this functional for the breaking of a single electron pair bond in N-electron molecules, using LiH, BeH{sup +}, and Li{sub 2} molecules as prototypes. Attention is given to the proper formulation of the functional in terms of not just J and K integrals but also the two-electron L integrals (K integrals with a different distribution of the complex conjugation of the orbitals), which is crucial for the calculation of response functions. Accurate energy curves are obtained with extended Löwdin-Shull functionals along the complete dissociation coordinate using full CI calculations as benchmark.

  14. Identifying potential selective fluorescent probes for cancer-associated protein carbonic anhydrase IX using a computational approach.

    Science.gov (United States)

    Kamstra, Rhiannon L; Floriano, Wely B

    2014-11-01

    Carbonic anhydrase IX (CAIX) is a biomarker for tumor hypoxia. Fluorescent inhibitors of CAIX have been used to study hypoxic tumor cell lines. However, these inhibitor-based fluorescent probes may have a therapeutic effect that is not appropriate for monitoring treatment efficacy. In the search for novel fluorescent probes that are not based on known inhibitors, a database of 20,860 fluorescent compounds was virtually screened against CAIX using hierarchical virtual ligand screening (HierVLS). The screening database contained 14,862 compounds tagged with the ATTO680 fluorophore plus an additional 5998 intrinsically fluorescent compounds. Overall ranking of compounds to identify hit molecular probe candidates utilized a principal component analysis (PCA) approach. Four potential binding sites, including the catalytic site, were identified within the structure of the protein and targeted for virtual screening. Available sequence information for 23 carbonic anhydrase isoforms was used to prioritize the four sites based on the estimated "uniqueness" of each site in CAIX relative to the other isoforms. A database of 32 known inhibitors and 478 decoy compounds was used to validate the methodology. A receiver-operating characteristic (ROC) analysis using the first principal component (PC1) as predictive score for the validation database yielded an area under the curve (AUC) of 0.92. AUC is interpreted as the probability that a binder will have a better score than a non-binder. The use of first component analysis of binding energies for multiple sites is a novel approach for hit selection. The very high prediction power for this approach increases confidence in the outcome from the fluorescent library screening. Ten of the top scoring candidates for isoform-selective putative binding sites are suggested for future testing as fluorescent molecular probe candidates.

  15. 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.

  16. 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.

  17. PATE, a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach

    Science.gov (United States)

    Bera, Tapan K.; Maitra, Rangan; Iavarone, Carlo; Salvatore, Giuliana; Kumar, Vasantha; Vincent, James J.; Sathyanarayana, B. K.; Duray, Paul; Lee, B. K.; Pastan, Ira

    2002-03-01

    To identify target antigens for prostate cancer therapy, we have combined computer-based screening of the human expressed sequence tag database and experimental expression analysis to identify genes that are expressed in normal prostate and prostate cancer but not in essential human tissues. Using this approach, we identified a gene that is expressed specifically in prostate cancer, normal prostate, and testis. The gene has a 1.5-kb transcript that encodes a protein of 14 kDa. We named this gene PATE (expressed in prostate and testis). In situ hybridization shows that PATE mRNA is expressed in the epithelial cells of prostate cancers and in normal prostate. Transfection of the PATE cDNA with a Myc epitope tag into NIH 3T3 cells and subsequent cell fractionation analysis shows that the PATE protein is localized in the membrane fraction of the cell. Analysis of the amino acid sequence of PATE shows that it has structural similarities to a group of proteins known as three-finger toxins, which includes the extracellular domain of the type transforming growth factor receptor. Restricted expression of PATE makes it a potential candidate for the immunotherapy of prostate cancer.

  18. 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

  19. 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; Antczak, 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

  20. 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

  1. 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 t...

  2. 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

  3. 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.

  4. A Kriging surrogate model coupled in simulation-optimization approach for identifying release history of groundwater sources

    Science.gov (United States)

    Zhao, Ying; Lu, Wenxi; Xiao, Chuanning

    2016-02-01

    As the incidence frequency of groundwater pollution increases, many methods that identify source characteristics of pollutants are being developed. In this study, a simulation-optimization approach was applied to determine the duration and magnitude of pollutant sources. Such problems are time consuming because thousands of simulation models are required to run the optimization model. To address this challenge, the Kriging surrogate model was proposed to increase computational efficiency. Accuracy, time consumption, and the robustness of the Kriging model were tested on both homogenous and non-uniform media, as well as steady-state and transient flow and transport conditions. The results of three hypothetical cases demonstrate that the Kriging model has the ability to solve groundwater contaminant source problems that could occur during field site source identification problems with a high degree of accuracy and short computation times and is thus very robust.

  5. Identifying New Candidate Genes and Chemicals Related to Prostate Cancer Using a Hybrid Network and Shortest Path Approach

    Science.gov (United States)

    Yuan, Fei; Zhou, You; Wang, Meng; Yang, Jing; Wu, Kai; Lu, Changhong; Kong, Xiangyin; Cai, Yu-Dong

    2015-01-01

    Prostate cancer is a type of cancer that occurs in the male prostate, a gland in the male reproductive system. Because prostate cancer cells may spread to other parts of the body and can influence human reproduction, understanding the mechanisms underlying this disease is critical for designing effective treatments. The identification of as many genes and chemicals related to prostate cancer as possible will enhance our understanding of this disease. In this study, we proposed a computational method to identify new candidate genes and chemicals based on currently known genes and chemicals related to prostate cancer by applying a shortest path approach in a hybrid network. The hybrid network was constructed according to information concerning chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions. Many of the obtained genes and chemicals are associated with prostate cancer. PMID:26504486

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. A Bayesian Approach for Analysis of Whole-Genome Bisulphite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation.

    Science.gov (United States)

    Rackham, Owen J L; Langley, Sarah R; Oates, Thomas; Vradi, Eleni; Harmston, Nathan; Srivastava, Prashant K; Behmoaras, Jacques; Dellaportas, Petros; Bottolo, Leonardo; Petretto, Enrico

    2017-02-17

    DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method's efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1,000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis) and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.

  9. Using a community-driven approach to identify local forest and climate change priorities in Teslin, Yukon

    Directory of Open Access Journals (Sweden)

    Joleen Timko

    2015-12-01

    Full Text Available The likelihood of addressing the complex environmental, economic, and social/cultural issues associated with local climate change impacts is enhanced when collaborative partnerships with local people are established. Using a community-centered approach in the Teslin region of Canada’s Yukon Territory, we utilized our research skills to respond to local needs for information by facilitating both an internal community process to clarify traditional and local knowledge, values, and perceptions on locally identified priorities, while gathering external information to enable local people to make sound decisions. Specifically, we sought to clarify local perceptions surrounding climate change impacts on fire risk and wildlife habitat, and the potential adaptation strategies appropriate and feasible within the Teslin Tlingit Traditional Territory. This paper provides a characterization of the study region and our project team; provides background on the interview and data collection process; presents our key results; and discusses the importance of our findings and charts a way forward for our continued work with the people in the Teslin region. This approach presents an excellent opportunity to help people holistically connect a range of local values, including fire risk mitigation, habitat enhancement, economic development, and enhanced social health.

  10. Immunogenic and invasive properties of Brucella melitensis 16M outer membrane protein vaccine candidates identified via a reverse vaccinology approach.

    Directory of Open Access Journals (Sweden)

    Gabriel Gomez

    Full Text Available Brucella is the etiologic agent of brucellosis, one of the most common and widely distributed zoonotic diseases. Its highly infectious nature, the insidious, systemic, chronic, debilitating aspects of the disease and the lack of an approved vaccine for human use in the United States are features that make Brucella a viable threat to public health. One of the main impediments to vaccine development is identification of suitable antigens. In order to identify antigens that could potentially be used in a vaccine formulation, we describe a multi-step antigen selection approach. We initially used an algorithm (Vaxign to predict ORF encoding outer membrane proteins with antigenic determinants. Differential gene expression during acute infection and published evidence for a role in virulence were used as criteria for down-selection of the candidate antigens that resulted from in silico prediction. This approach resulted in the identification of nine Brucella melitensis outer membrane proteins, 5 of which were recombinantly expressed and used for validation. Omp22 and Hia had the highest in silico scores for adhesin probability and also conferred invasive capacity to E. coli overexpressing recombinant proteins. With the exception of FlgK in the goat, all proteins reacted to pooled sera from exposed goats, mice, and humans. BtuB, Hia and FlgK stimulated a mixed Th1-Th2 response in splenocytes from immunized mice while BtuB and Hia elicited NO release from splenocytes of S19 immunized mice. The results support the applicability of the current approach to the identification of antigens with immunogenic and invasive properties. Studies to assess immunogenicity and protective efficacy of individual proteins in the mouse are currently underway.

  11. Immunogenic and invasive properties of Brucella melitensis 16M outer membrane protein vaccine candidates identified via a reverse vaccinology approach.

    Science.gov (United States)

    Gomez, Gabriel; Pei, Jianwu; Mwangi, Waithaka; Adams, L Garry; Rice-Ficht, Allison; Ficht, Thomas A

    2013-01-01

    Brucella is the etiologic agent of brucellosis, one of the most common and widely distributed zoonotic diseases. Its highly infectious nature, the insidious, systemic, chronic, debilitating aspects of the disease and the lack of an approved vaccine for human use in the United States are features that make Brucella a viable threat to public health. One of the main impediments to vaccine development is identification of suitable antigens. In order to identify antigens that could potentially be used in a vaccine formulation, we describe a multi-step antigen selection approach. We initially used an algorithm (Vaxign) to predict ORF encoding outer membrane proteins with antigenic determinants. Differential gene expression during acute infection and published evidence for a role in virulence were used as criteria for down-selection of the candidate antigens that resulted from in silico prediction. This approach resulted in the identification of nine Brucella melitensis outer membrane proteins, 5 of which were recombinantly expressed and used for validation. Omp22 and Hia had the highest in silico scores for adhesin probability and also conferred invasive capacity to E. coli overexpressing recombinant proteins. With the exception of FlgK in the goat, all proteins reacted to pooled sera from exposed goats, mice, and humans. BtuB, Hia and FlgK stimulated a mixed Th1-Th2 response in splenocytes from immunized mice while BtuB and Hia elicited NO release from splenocytes of S19 immunized mice. The results support the applicability of the current approach to the identification of antigens with immunogenic and invasive properties. Studies to assess immunogenicity and protective efficacy of individual proteins in the mouse are currently underway.

  12. A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network.

    Science.gov (United States)

    Unnikrishnan, Ashwin; Guan, Yi F; Huang, Yizhou; Beck, Dominik; Thoms, Julie A I; Peirs, Sofie; Knezevic, Kathy; Ma, Shiyong; de Walle, Inge V; de Jong, Ineke; Ali, Zara; Zhong, Ling; Raftery, Mark J; Taghon, Tom; Larsson, Jonas; MacKenzie, Karen L; Van Vlierberghe, Pieter; Wong, Jason W H; Pimanda, John E

    2016-12-15

    Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34(+) haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis.

  13. 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.

  14. An operational research approach to identify cardiac surgery patients at risk of severe post-operative bleeding.

    Science.gov (United States)

    Reddy, Brian; Pagel, Christina; Vuylsteke, Alain; Gerrard, Caroline; Nashef, Sam; Utley, Martin

    2011-09-01

    Severe post-operative bleeding can lead to adverse outcomes for cardiac surgery patients and is a relatively common complication of cardiac surgery. One of the most effective drugs to prevent such bleeding, aprotinin, has been withdrawn from the market due to concerns over its safety. Alternative prophylactic drugs which can be given to patients to prevent bleeding can result in significant side effects and are expensive. For this reason it is difficult to make a clinical or economic case for administering these drugs to all cardiac surgery patients, and the prevailing view is that their use should be targeted at patients considered to be at relatively high risk of post-operative bleeding. However, there is currently no objective method for identifying such patients. Over the past 7 years, a team of clinicians and researchers at Papworth Hospital has collected data concerning post-operative blood loss for each cardiac surgery patient, totalling 11,592 consecutive records. They approached a team of operational researchers (MU, ACP, BR) with extensive experience of developing clinical risk models with the aim of devising a risk stratification scheme that could potentially be used to identify a cohort of higher risk patients. Such patients could be treated with the available prophylactic drugs or recruited to studies to evaluate new interventions. This paper is intended to describe the Operational Research process adopted in the development of this scheme. A concise description of the scheme and its clinical interpretation is published elsewhere.

  15. Identifying Unique Neighborhood Characteristics to Guide Health Planning for Stroke and Heart Attack: Fuzzy Cluster and Discriminant Analyses Approaches

    Science.gov (United States)

    Pedigo, Ashley; Seaver, William; Odoi, Agricola

    2011-01-01

    Background Socioeconomic, demographic, and geographic factors are known determinants of stroke and myocardial infarction (MI) risk. Clustering of these factors in neighborhoods needs to be taken into consideration during planning, prioritization and implementation of health programs intended to reduce disparities. Given the complex and multidimensional nature of these factors, multivariate methods are needed to identify neighborhood clusters of these determinants so as to better understand the unique neighborhood profiles. This information is critical for evidence-based health planning and service provision. Therefore, this study used a robust multivariate approach to classify neighborhoods and identify their socio-demographic characteristics so as to provide information for evidence-based neighborhood health planning for stroke and MI. Methods and Findings The study was performed in East Tennessee Appalachia, an area with one of the highest stroke and MI risks in USA. Robust principal component analysis was performed on neighborhood (census tract) socioeconomic and demographic characteristics, obtained from the US Census, to reduce the dimensionality and influence of outliers in the data. Fuzzy cluster analysis was used to classify neighborhoods into Peer Neighborhoods (PNs) based on their socioeconomic and demographic characteristics. Nearest neighbor discriminant analysis and decision trees were used to validate PNs and determine the characteristics important for discrimination. Stroke and MI mortality risks were compared across PNs. Four distinct PNs were identified and their unique characteristics and potential health needs described. The highest risk of stroke and MI mortality tended to occur in less affluent PNs located in urban areas, while the suburban most affluent PNs had the lowest risk. Conclusions Implementation of this multivariate strategy provides health planners useful information to better understand and effectively plan for the unique

  16. Identifiability of sorption parameters in stirred flow-through reactor experiments and their identification with a Bayesian approach.

    Science.gov (United States)

    Nicoulaud-Gouin, V; Garcia-Sanchez, L; Giacalone, M; Attard, J C; Martin-Garin, A; Bois, F Y

    2016-10-01

    This paper addresses the methodological conditions -particularly experimental design and statistical inference- ensuring the identifiability of sorption parameters from breakthrough curves measured during stirred flow-through reactor experiments also known as continuous flow stirred-tank reactor (CSTR) experiments. The equilibrium-kinetic (EK) sorption model was selected as nonequilibrium parameterization embedding the Kd approach. Parameter identifiability was studied formally on the equations governing outlet concentrations. It was also studied numerically on 6 simulated CSTR experiments on a soil with known equilibrium-kinetic sorption parameters. EK sorption parameters can not be identified from a single breakthrough curve of a CSTR experiment, because Kd,1 and k(-) were diagnosed collinear. For pairs of CSTR experiments, Bayesian inference allowed to select the correct models of sorption and error among sorption alternatives. Bayesian inference was conducted with SAMCAT software (Sensitivity Analysis and Markov Chain simulations Applied to Transfer models) which launched the simulations through the embedded simulation engine GNU-MCSim, and automated their configuration and post-processing. Experimental designs consisting in varying flow rates between experiments reaching equilibrium at contamination stage were found optimal, because they simultaneously gave accurate sorption parameters and predictions. Bayesian results were comparable to maximum likehood method but they avoided convergence problems, the marginal likelihood allowed to compare all models, and credible interval gave directly the uncertainty of sorption parameters θ. Although these findings are limited to the specific conditions studied here, in particular the considered sorption model, the chosen parameter values and error structure, they help in the conception and analysis of future CSTR experiments with radionuclides whose kinetic behaviour is suspected.

  17. 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

  18. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks.

    Directory of Open Access Journals (Sweden)

    Dimitrios Iliopoulos

    Full Text Available BACKGROUND: Osteoarthritis is a multifactorial disease characterized by destruction of the articular cartilage due to genetic, mechanical and environmental components affecting more than 100 million individuals all over the world. Despite the high prevalence of the disease, the absence of large-scale molecular studies limits our ability to understand the molecular pathobiology of osteoathritis and identify targets for drug development. METHODOLOGY/PRINCIPAL FINDINGS: In this study we integrated genetic, bioinformatic and proteomic approaches in order to identify new genes and their collaborative networks involved in osteoarthritis pathogenesis. MicroRNA profiling of patient-derived osteoarthritic cartilage in comparison to normal cartilage, revealed a 16 microRNA osteoarthritis gene signature. Using reverse-phase protein arrays in the same tissues we detected 76 differentially expressed proteins between osteoarthritic and normal chondrocytes. Proteins such as SOX11, FGF23, KLF6, WWOX and GDF15 not implicated previously in the genesis of osteoarthritis were identified. Integration of microRNA and proteomic data with microRNA gene-target prediction algorithms, generated a potential "interactome" network consisting of 11 microRNAs and 58 proteins linked by 414 potential functional associations. Comparison of the molecular and clinical data, revealed specific microRNAs (miR-22, miR-103 and proteins (PPARA, BMP7, IL1B to be highly correlated with Body Mass Index (BMI. Experimental validation revealed that miR-22 regulated PPARA and BMP7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that obesity and inflammation are related to osteoarthritis, a metabolic disease affected by microRNA deregulation. Gene network approaches provide new insights for elucidating the complexity of diseases such as osteoarthritis. The integration of microRNA, proteomic

  19. 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.

  20. 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)...

  1. Axial coordination dichotomy in dirhodium carbenoid catalysis: a curious case of cooperative asymmetric dual-catalytic approach toward amino esters.

    Science.gov (United States)

    Kisan, Hemanta K; Sunoj, Raghavan B

    2015-02-20

    One of the most recent developments in asymmetric catalysis is to employ two or more catalysts under one-pot reaction conditions. This article presents some interesting mechanistic insights on a cooperative dual-catalytic protocol relying on the catalytic ability of dirhodium carbenoid (derived from rhodium(II) tetracarboxylate and a diazo compound) and a chiral spirophosphoric acid ((R)-SPA) in an asymmetric N-H insertion reaction. We have employed DFT(M06 and B3LYP) computational methods to identify the stereocontrolling transition states wherein a chiral (R)-SPA protonates a dirhodium-bound enol intermediate. A true cooperative action elicited by both catalysts has been noted in the enantioselective protonation. More importantly, whether the second axial ligand on the remote rhodium atom could influence the energetic features of the reaction has been probed for the first time. In all steps (such as nitrogen extrusion, addition of amine to the dirhodium carbenoid, and the enol formation), except that in the stereocontrolling event, no major effect of axial ligation has been noticed. However, the presence of the axial ligand helps in stabilizing the protonation transition state and reduces the activation barrier for protonation, suggesting a vital role in stereoselectivity. The predicted sense of stereoselectivities is in good agreement with the experimental results.

  2. 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

  3. 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

  4. 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.

  5. 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 .

  6. Multipronged approach to identify and validate a novel upstream regulator of Sncg in mouse retinal ganglion cells.

    Science.gov (United States)

    Chintalapudi, Sumana R; Morales-Tirado, Vanessa M; Williams, Robert W; Jablonski, Monica M

    2016-02-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Mechanistic studies on RGCs are hindered by the lack of sufficient primary cells and consensus regarding their signature markers. Recently, γ-synuclein (SNCG) has been shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the role of Sncg in RGCs, we used a novel systems genetics approach to identify a gene that modulates Sncg expression, followed by confirmatory studies in both healthy and diseased retinae. We found that chromosome 1 harbors an expression quantitative trait locus that modulates Sncg expression in the mouse retina, and identified the prefoldin-2 (PFDN2) gene as the candidate upstream modulator of Sncg expression. Our immunohistochemical analyses revealed similar expression patterns in both mouse and human healthy retinae, with PFDN2 colocalizing with SNCG in RGCs and their axons. In contrast, in retinae from glaucoma subjects, SNCG levels were significantly reduced, although PFDN2 levels were maintained. Using a novel flow cytometry-based RGC isolation method, we obtained viable populations of murine RGCs. Knocking down Pfdn2 expression in primary murine RGCs significantly reduced Sncg expression, confirming that Pfdn2 regulates Sncg expression in murine RGCs. Gene Ontology analysis indicated shared mitochondrial function associated with Sncg and Pfdn2. These data solidify the relationship between Sncg and Pfdn2 in RGCs, and provide a novel mechanism for maintaining RGC health.

  7. Innovative new technologies to identify and treat traumatic brain injuries: crossover technologies and approaches between military and civilian applications.

    Science.gov (United States)

    Doarn, Charles R; McVeigh, Francis; Poropatich, Ronald

    2010-04-01

    Traumatic brain injury (TBI) has become the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom. The use of improvised explosive devices has seen an exponential increase in both Iraq and Afghanistan. In previous conflicts prior to Iraq, survivability of such an injury was far less. Today, technological improvements in trauma care have increased an injured warfighter's chance of survival. A reduction in severe TBI has been achieved but an increase in mild or moderate TBI has been observed. The consequences of this kind of injury can be both physical and mental and can often be hidden or even misdiagnosed. The U.S. Army is interested in pursuing technological solutions for early detection and treatment of TBI to reduce its lasting impact on the warfighter. Such technological breakthroughs have benefit beyond the military, as TBI is a high probable event in nonmilitary settings as well. To gauge what technologies or methods are currently available, the U.S. Army's Telemedicine and Advanced Technology Research Center partnered with the American Telemedicine Association to organize and conduct a discipline-specific symposium entitled "Innovative New Technologies to Identify and Treat Traumatic Brain Injuries: Crossover Technologies and Approaches Between Military and Civilian Applications." This symposium was held in Palm Springs, CA, in September 2009. The purpose of the meeting was to provide a unique opportunity for leaders from disparate organizations involved in telemedicine and related other activities to meet and explore opportunities to collaborate in new partnership models. The meeting was designed to help Telemedicine and Advanced Technology Research Center identify opportunities to expand strategic operations and form new alliances. This report summarizes this symposium while raising awareness for collaboration into better ways of adapting and adopting technologies to address this growing health issue.

  8. 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.

  9. 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.

  10. 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.

  11. Coordinate-Free Rotation Operator.

    Science.gov (United States)

    Leubner, C.

    1979-01-01

    Suggests the use of a coordinate-free rotation operator for the teaching of rotations in Euclidean three space because of its twofold didactic advantage. Illustrates the potentialities of the coordinate-free rotation operator approach by a number of examples. (Author/GA)

  12. 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 ...

  13. Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Firas H Kobeissy

    2016-11-01

    Full Text Available Traumatic brain injury (TBI represents a critical health problem of which diagnosis, management and treatment remain challenging. TBI is a contributing factor in approximately 1/3 of all injury-related deaths in the United States. The Centers for Disease Control and Prevention (CDC estimate that 1.7 million TBI people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system (CNS injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day and for the first time, subacute (7 days, post-injury time frame using the established CAX-PAGE LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entities, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day and subacute (7 days periods post TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7-days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is amongst the first to assess temporal neuroproteome

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Developmental coordination disorder: what is it?

    Science.gov (United States)

    Dewey, D; Wilson, B N

    2001-01-01

    This paper begins with a discussion of the historical basis for the concept of developmental coordination disorder (DCD). The definition of this disorder as it appears in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) is then provided. The four diagnostic criteria proposed by the DSM-IV are used to describe the disorder. Problems associated with the assessment of DCD are discussed and suggestions for further research are identified. This is followed by a discussion of intervention approaches that can be used with children identified with DCD.

  19. Novel in vivo targets of ΔNp63 in keratinocytes identified by a modified chromatin immunoprecipitation approach

    Directory of Open Access Journals (Sweden)

    Ortt Kori

    2007-05-01

    Full Text Available Abstract Background p63 is a transcription factor that plays an important role in skin epidermal development and differentiation. The p63 gene encodes for two major protein isoforms, those containing an amino-terminal trans-activation domain (TAp63 and those lacking this domain (ΔNp63. Both the TA and ΔN transcripts are also alternatively spliced at the 3' end producing proteins with unique C-termini that are designated as α, β and γ isoforms. Recent research has suggested that ΔNp63 is the predominant isoform expressed and active in keratinocytes. Results To better elucidate the biological role of p63 in regulating gene expression in keratinocytes we performed chromatin immunoprecipitation (ChIP experiments with ΔNp63-specific antibodies. We included an additional step in the ChIP procedure to enrich for ΔNp63 targets by screening the library of immunoprecipitated DNA for its ability to bind recombinant GST-ΔNp63. Cloning of ΔNp63-ChIP-derived DNA fragments identified more than 60 potential ΔNp63 target loci that were located close to or embedded within known or predicted genes. Identity of these target genes suggests that they may participate in a myriad of cellular processes including transcriptional regulation, signaling and metabolism. Here we confirm the binding of ΔNp63 to several of these genomic loci both by EMSA and replicate ChIP assays. Finally we show that the expression of many of these target genes is altered when ΔNp63 levels in keratinocytes are reduced by siRNA, further confirming that these are bona fide targets. Conclusion This unbiased genomic approach has allowed us to uncover functional targets of ΔNp63 and serves as the initial step in further analysis of the transcriptional regulatory mechanisms that are governed by p63 in keratinocytes.

  20. Identifying food proteins with allergenic potential: evolution of approaches to safety assessment and research to provide additional tools.

    Science.gov (United States)

    Ladics, Gregory S; Selgrade, MaryJane K

    2009-08-01

    A safety assessment process exists for genetically engineered crops that includes the evaluation of the expressed protein for allergenic potential. The objectives of this evaluation are twofold: (1) to protect allergic consumers from exposure to known allergenic or cross-reactive proteins, and (2) protect the general population from risks associated with the introduction of genes encoding proteins that are likely to become food allergens. The first systematic approach to address these concerns was formulated by Metcalfe et al. [Metcalfe, D.D., Astwood, J.D., Townsend, R., Sampson, H.A., Taylor, S.L., and Fuchs, R.L. 1996. Assessment of the allergenic potential of foods from genetically engineered crop plants. Crit. Rev. Food Sci. Nutr. 36(5), 165-186.] and subsequently Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) [FAO/WHO, 2001. Evaluation of allergenicity of genetically modified foods. Report of a Joint FAO/WHO Expert Consultation on Allergenicity of Foods Derived from Biotechnology. January 22-25, 2001. Rome, Italy]. More recently, Codex [Codex Alimentarius Commission, 2003. Alinorm 03/34: Joint FAO/WHO Food Standard Programme, Codex Alimentarius Commission, Twenty-Fifth Session, Rome, Italy, 30 June-5 July, 2003. Appendix III, Guideline for the conduct of food safety assessment of foods derived from recombinant-DNA plants, and Appendix IV, Annex on the assessment of possible allergenicity. pp. 47-60], noting that no single factor is recognized as an identifier for protein allergenicity, suggested a weight of evidence approach be conducted that takes into account a variety of factors and approaches for an overall assessment of allergenic potential. These various recommendations are based on what is known about allergens, including the history of exposure and safety of the gene(s) source; amino acid sequence identity to human allergens; stability to pepsin digestion in vitro; protein abundance in the crop and

  1. 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

  2. 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...

  3. 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.

  4. 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.

  5. Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads

    Directory of Open Access Journals (Sweden)

    Patton E Elizabeth

    2010-06-01

    Full Text Available Abstract In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification.

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. Homepage Coordination

    Science.gov (United States)

    Hodas, Steven

    1995-01-01

    This paper describes efforts to identify issues and design implementation strategies to better promote the NASA IITA K-12 project on the world wide web and, in so doing, better serve our constituents.

  11. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik;

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD...

  12. RUN COORDINATION

    CERN Multimedia

    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...

  13. 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...

  14. 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…

  15. Combining a Ru(II) "Building Block" and Rapid Screening Approach to Identify DNA Structure-Selective "Light Switch" Compounds.

    Science.gov (United States)

    Wachter, Erin; Moyá, Diego; Glazer, Edith C

    2017-02-13

    A chemically reactive Ru(II) "building block", able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent "light switch" dipyrido-[3,2-a:2',3'-c] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA. Combining these two approaches allowed for the identification of hit molecules that showed different selectivities for biologically relevant DNA structures, particularly triplex and quadruplex DNA.

  16. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    OpenAIRE

    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

    2012-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-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 associat...

  17. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    DEFF Research Database (Denmark)

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A;

    2012-01-01

    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 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....

  18. A bottom-up approach to identifying the maximum operational adaptive capacity of water resource systems to a changing climate

    Science.gov (United States)

    Culley, S.; Noble, S.; Yates, A.; Timbs, M.; Westra, S.; Maier, H. R.; Giuliani, M.; Castelletti, A.

    2016-09-01

    Many water resource systems have been designed assuming that the statistical characteristics of future inflows are similar to those of the historical record. This assumption is no longer valid due to large-scale changes in the global climate, potentially causing declines in water resource system performance, or even complete system failure. Upgrading system infrastructure to cope with climate change can require substantial financial outlay, so it might be preferable to optimize existing system performance when possible. This paper builds on decision scaling theory by proposing a bottom-up approach to designing optimal feedback control policies for a water system exposed to a changing climate. This approach not only describes optimal operational policies for a range of potential climatic changes but also enables an assessment of a system's upper limit of its operational adaptive capacity, beyond which upgrades to infrastructure become unavoidable. The approach is illustrated using the Lake Como system in Northern Italy—a regulated system with a complex relationship between climate and system performance. By optimizing system operation under different hydrometeorological states, it is shown that the system can continue to meet its minimum performance requirements for more than three times as many states as it can under current operations. Importantly, a single management policy, no matter how robust, cannot fully utilize existing infrastructure as effectively as an ensemble of flexible management policies that are updated as the climate changes.

  19. 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.

  20. Novel seminal fluid proteins in the seed beetle Callosobruchus maculatus identified by a proteomic and transcriptomic approach.

    Science.gov (United States)

    Bayram, H; Sayadi, A; Goenaga, J; Immonen, E; Arnqvist, G

    2017-02-01

    The seed beetle Callosobruchus maculatus is a significant agricultural pest and increasingly studied model of sexual conflict. Males possess genital spines that increase the transfer of seminal fluid proteins (SFPs) into the female body. As SFPs alter female behaviour and physiology, they are likely to modulate reproduction and sexual conflict in this species. Here, we identified SFPs using proteomics combined with a de novo transcriptome. A prior 2D-sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis identified male accessory gland protein spots that were probably transferred to the female at mating. Proteomic analysis of these spots identified 98 proteins, a majority of which were also present within ejaculates collected from females. Standard annotation workflows revealed common functional groups for SFPs, including proteases and metabolic proteins. Transcriptomic analysis found 84 transcripts differentially expressed between the sexes. Notably, genes encoding 15 proteins were highly expressed in male abdomens and only negligibly expressed within females. Most of these sequences corresponded to 'unknown' proteins (nine of 15) and may represent rapidly evolving SFPs novel to seed beetles. Our combined analyses highlight 44 proteins for which there is strong evidence that they are SFPs. These results can inform further investigation, to better understand the molecular mechanisms of sexual conflict in seed beetles.

  1. Circular permutation prediction reveals a viable backbone disconnection for split proteins: an approach in identifying a new functional split intein.

    Directory of Open Access Journals (Sweden)

    Yun-Tzai Lee

    Full Text Available Split-protein systems have emerged as a powerful tool for detecting biomolecular interactions and reporting biological reactions. However, reliable methods for identifying viable split sites are still unavailable. In this study, we demonstrated the feasibility that valid circular permutation (CP sites in proteins have the potential to act as split sites and that CP prediction can be used to search for internal permissive sites for creating new split proteins. Using a protein ligase, intein, as a model, CP predictor facilitated the creation of circular permutants in which backbone opening imposes the least detrimental effects on intein folding. We screened a series of predicted intein CPs and identified stable and native-fold CPs. When the valid CP sites were introduced as split sites, there was a reduction in folding enthalpy caused by the new backbone opening; however, the coincident loss in entropy was sufficient to be compensated, yielding a favorable free energy for self-association. Since split intein is exploited in protein semi-synthesis, we tested the related protein trans-splicing (PTS activities of the corresponding split inteins. Notably, a novel functional split intein composed of the N-terminal 36 residues combined with the remaining C-terminal fragment was identified. Its PTS activity was shown to be better than current reported two-piece intein with a short N-terminal segment. Thus, the incorporation of in silico CP prediction facilitated the design of split intein as well as circular permutants.

  2. Review on Pricing Approach and Coordination Strategy of Dual-channel Supply Chain%双渠道供应链定价策略与协调机制研究综述

    Institute of Scientific and Technical Information of China (English)

    胡东波; 翟雯瑶

    2013-01-01

    梳理国内外相关文献,对双渠道供应链中的定价策略以及协调方法的研究现状进行综述,比较需求函数的影响因素,分类定价的不同策略,总结各种协调方法.在此基础上,展望未来的研究发展.%The paper reviews the relevant literature, overviews pricing approaches and coordinated strategies in the dual - channel supply chain, compares the influence factors of the demand function, classifies the pricing approaches and summarizes the various methods of coordination, the paper also researches the direction of future development in thie domain.

  3. Evaluation of direct and indirect ethanol biomarkers using a likelihood ratio approach to identify chronic alcohol abusers for forensic purposes.

    Science.gov (United States)

    Alladio, Eugenio; Martyna, Agnieszka; Salomone, Alberto; Pirro, Valentina; Vincenti, Marco; Zadora, Grzegorz

    2017-02-01

    The detection of direct ethanol metabolites, such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), in scalp hair is considered the optimal strategy to effectively recognize chronic alcohol misuses by means of specific cut-offs suggested by the Society of Hair Testing. However, several factors (e.g. hair treatments) may alter the correlation between alcohol intake and biomarkers concentrations, possibly introducing bias in the interpretative process and conclusions. 125 subjects with various drinking habits were subjected to blood and hair sampling to determine indirect (e.g. CDT) and direct alcohol biomarkers. The overall data were investigated using several multivariate statistical methods. A likelihood ratio (LR) approach was used for the first time to provide predictive models for the diagnosis of alcohol abuse, based on different combinations of direct and indirect alcohol biomarkers. LR strategies provide a more robust outcome than the plain comparison with cut-off values, where tiny changes in the analytical results can lead to dramatic divergence in the way they are interpreted. An LR model combining EtG and FAEEs hair concentrations proved to discriminate non-chronic from chronic consumers with ideal correct classification rates, whereas the contribution of indirect biomarkers proved to be negligible. Optimal results were observed using a novel approach that associates LR methods with multivariate statistics. In particular, the combination of LR approach with either Principal Component Analysis (PCA) or Linear Discriminant Analysis (LDA) proved successful in discriminating chronic from non-chronic alcohol drinkers. These LR models were subsequently tested on an independent dataset of 43 individuals, which confirmed their high efficiency. These models proved to be less prone to bias than EtG and FAEEs independently considered. In conclusion, LR models may represent an efficient strategy to sustain the diagnosis of chronic alcohol consumption

  4. 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.

  5. A molecular and phenotypic integrative approach to identify a no-effect dose level for antiandrogen-induced testicular toxicity.

    Science.gov (United States)

    Ludwig, Sophie; Tinwell, Helen; Schorsch, Frédéric; Cavaillé, Christel; Pallardy, Marc; Rouquié, David; Bars, Rémi

    2011-07-01

    The safety assessment of chemicals for humans relies on identifying no-observed adverse effect levels (NOAELs) in animal toxicity studies using standard methods. With the advent of high information content technologies, especially microarrays, it is pertinent to determine the impact of molecular data on the NOAELs. Consequently, we conducted an integrative study to identify a no-transcriptomic effect dose using microarray analyses coupled with quantitative reverse transcriptase PCR (RT-qPCR) and determined how this correlated with the NOAEL. We assessed the testicular effects of the antiandrogen, flutamide (FM), in a rat 28-day toxicity study using doses of 0.2-30 mg/kg/day. Plasma testosterone levels and testicular histopathology indicated a NOAEL of 1 mg/kg/day. A no-effect dose of 0.2 mg/kg/day was established based on molecular data relevant to the phenotypic changes. We observed differential gene expression starting from 1 mg/kg/day and a deregulation of more than 1500 genes at 30 mg/kg/day. Dose-related changes were identified for the major pathways (e.g., fatty acid metabolism) associated with the testicular lesion (Leydig cell hyperplasia) that were confirmed by RT-qPCR. These data, along with protein accumulation profiles and FM metabolite concentrations in testis, supported the no-effect dose of 0.2 mg/kg/day. Furthermore, the microarray data indicated a dose-dependent change in the fatty acid catabolism pathway, a biological process described for the first time to be affected by FM in testicular tissue. In conclusion, the present data indicate the existence of a transcriptomic threshold, which must be exceeded to progress from a normal state to an adaptative state and subsequently to adverse toxicity.

  6. 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.

  7. A combined GIS and stereo vision approach to identify building pixels in images and determine appropriate color terms

    Directory of Open Access Journals (Sweden)

    Philip James Bartie

    2011-05-01

    Full Text Available Color information is a useful attribute to include in a building's description to assist the listener in identifying the intended target. Often this information is only available as image data, and not readily accessible for use in constructing referring expressions for verbal communication. The method presented uses a GIS building polygon layer in conjunction with street-level captured imagery to provide a method to automatically filter foreground objects and select pixels which correspond to building facades. These selected pixels are then used to define the most appropriate color term for the building, and corresponding fuzzy color term histogram. The technique uses a single camera capturing images at a high frame rate, with the baseline distance between frames calculated from a GPS speed log. The expected distance from the camera to the building is measured from the polygon layer and refined from the calculated depth map, after which building pixels are selected. In addition significant foreground planar surfaces between the known road edge and building facade are identified as possible boundary walls and hedges. The output is a dataset of the most appropriate color terms for both the building and boundary walls. Initial trials demonstrate the usefulness of the technique in automatically capturing color terms for buildings in urban regions.

  8. A combined GIS and stereo vision approach to identify building pixels in images and determine appropriate color terms

    Directory of Open Access Journals (Sweden)

    Philip James Bartie

    2011-01-01

    Full Text Available Color information is a useful attribute to include in a building's description to assist the listener in identifying the intended target. Often this information is only available as image data, and not readily accessible for use in constructing referring expressions for verbal communication. The method presented uses a GIS building polygon layer in conjunction with street-level captured imagery to provide a method to automatically filter foreground objects and select pixels which correspond to building facades. These selected pixels are then used to define the most appropriate color term for the building, and corresponding fuzzy color term histogram. The technique uses a single camera capturing images at a high frame rate, with the baseline distance between frames calculated from a GPS speed log. The expected distance from the camera to the building is measured from the polygon layer and refined from the calculated depth map, after which building pixels are selected. In addition significant foreground planar surfaces between the known road edge and building facade are identified as possible boundary walls and hedges. The output is a dataset of the most appropriate color terms for both the building and boundary walls. Initial trials demonstrate the usefulness of the technique in automatically capturing color terms for buildings in urban regions.

  9. [Feasibility study on an approach for identifying corn kernel varieties with seed coating agents via near infrared spectroscopy].

    Science.gov (United States)

    Jia, Shi-Qiang; Guo, Ting-Ting; Liu, Zhe; Yan, Yan-Lu; An, Dong; Gu, Jian-Cheng; Li, Shao-ming; Zhang, Shao-Ming; Zhu, De-Hai

    2014-11-01

    It is generally accepted that near infrared reflectance spectroscopy (NIRS) can be used to identify variety authenticity of bare maize seeds. In practical, maize seeds are covered with seed coating agents. Therefore it's of huge significance to investigate the feasibility of identifying coated maize seeds by NIRS. This study employed NIRS to quickly determine the variety of coated maize seeds. Influence of seed coating agent on NIR spectra was discussed. The NIR spectra of coated maize seeds were obtained using an innovative method to avoid the impact of the seed coating agent. Coated seeds were cut open, and the sections were scanned by the spectrometer, so as to acquire the information of the seed itself. Then, support vector machine (SVM), soft independent modeling of class analogy (SIMCA), and biomimetic pattern recognition (BPR) was employed to establish the identification model for four maize varieties, and yield 93%, 95.8%, 98% average correct rate respectively. BPR model showed better performance than SVM and SIMCA models. The robustness of identification model was tested by seeds harvested from four regions and model showed good performance.

  10. Molecular approaches identify known species, reveal cryptic species and verify host specificity of Chinese Philotrypesis (Hymenoptera: Pteromalidae).

    Science.gov (United States)

    Zhou, Mei-Jiao; Xiao, Jin-Hua; Bian, Sheng-Nan; Li, Yan-Wei; Niu, Li-Ming; Hu, Hao-Yuan; Wu, Wen-Shan; Murphy, Robert W; Huang, Da-Wei

    2012-07-01

    Philotrypesis, a major component of the fig wasp community (Hymenoptera: Pteromalidae), is a model taxon for studying male fighting and mating behaviour. Its extreme sexual dimorphism and male polymorphism render species identification uncertain and in-depth research on its ecology, behaviour and other evolutionary topics challenging. The fig wasps' enclosed habitat within the syconia makes their mating behaviour inaccessible, to the extent of matching conspecific females and males. In this study, we combine morphological and molecular analyses to identify species of Philotrypesis sampled from south China and to associate their extraordinarily dimorphic genders and labile male morphologies. Morphological evaluations of females identify 22 species and 28 male morphs. The mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 2 data detect 21 species using females, and 15 species among the males. Most of the males match the species as delimited by females. Both markers reveal cryptic species in P. quadrisetosa on Ficus vasculosa. Most species of wasps live on one species of fig but three species co-occur in two hosts (F. microcarpa and F. benjamina), which indicates host switching.

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. Motor coordination: a local hub for coordination.

    Science.gov (United States)

    Calabrese, Ronald L

    2014-03-31

    A local interneuron of a crayfish central pattern generator serves as a hub that integrates ascending and descending coordinating information and passes it on to a local oscillatory microcircuit to coordinate a series of segmental appendages known as swimmerets.

  16. “I know it when I see it”: Identifying ocean wilderness using a photo-based survey approach

    Directory of Open Access Journals (Sweden)

    Bradley W. Barr

    2014-12-01

    Full Text Available “Wilderness” is identified and defined, in large part, as places perceived by people as possessing characteristic qualities and attributes such as remoteness, providing opportunities for solitude, and where the influence of man is not readily apparent. It has been suggested that “wilderness is what people think it is.” To better understand how this idea of wilderness can be most appropriately applied to ocean and coastal waters, a photo-based online survey was conducted, targeting a sample of protected area resource managers and scientists. The survey results suggested that the respondents overwhelmingly and strongly perceived coastal waters, and particularly waters adjacent to designated coastal wilderness areas, as “wilderness.” Offshore areas were also perceived as possessing value as potential wilderness, but somewhat less often than places located near the coast.

  17. Identifying patients suitable for palliative care - a descriptive analysis of enquiries using a Case Management Process Model approach

    Directory of Open Access Journals (Sweden)

    Kuhn Ulrike

    2012-11-01

    Full Text Available Abstract Background In Germany, case management in a palliative care unit was first implemented in 2005 at the Department of Palliative Medicine at the University Hospital Cologne. One of the purposes of this case management is to deal with enquiries from patients and their relatives as well as medical professionals. Using the Case Management Process Model of the Case Management Society of America as a reference, this study analysed (a how this case management was used by different enquiring groups and (b how patients were identified for case management and for palliative care services. The first thousand enquiries were analysed considering patient variables, properties of the enquiring persons and the content of the consultations. Results Most enquiries to the case management were made by telephone. The majority of requests regarded patients with oncological disease (84.3 %. The largest enquiring group was composed of patients and relatives (40.8 %, followed by internal professionals of the hospital (36.1 %. Most of the enquiring persons asked for a patient’s admission to the palliative care ward (46.4 %. The second most frequent request was for consultation and advice (30.9 %, followed by requests for the palliative home care service (13.3 %. Frequent reasons for actual admissions were the need for the treatment of pain, the presence of symptoms and the need for nursing care. More than half of the enquiries concerning admission to the palliative care ward were followed by an admission. Conclusions Case management has been made public among the relevant target groups. Case management as described by the Case Management Process Model helps to identify patients likely to benefit from case management and palliative care services. In addition, with the help of case management palliative patients may be allocated to particular health care services.

  18. A microbial signature approach to identify fecal pollution in the waters off an urbanized coast of Lake Michigan.

    Science.gov (United States)

    Newton, Ryan J; Bootsma, Melinda J; Morrison, Hilary G; Sogin, Mitchell L; McLellan, Sandra L

    2013-05-01

    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 distributions that signal the presence of sewer, fecal, and human fecal pollution. The sequences classified to three sewer infrastructure-associated bacterial genera, Acinetobacter, Arcobacter, and Trichococcus, and five fecal-associated bacterial families, Bacteroidaceae, Porphyromonadaceae, Clostridiaceae, Lachnospiraceae, and Ruminococcaceae, served as signatures of sewer and fecal contamination, respectively. The human fecal signature was determined with the Bayesian source estimation program SourceTracker, which we applied to a set of 40 sewage influent samples collected in Milwaukee, WI, USA to identify operational taxonomic units (≥ 97 % identity) that were most likely of human fecal origin. During periods of dry weather, the magnitudes of all three signatures were relatively low in Milwaukee's urban rivers and harbor and nearly zero in Lake Michigan. However, the relative contribution of the sewer and fecal signature frequently increased to > 2 % of the measured surface water communities following sewer overflows. Also during combined sewer overflows, the ratio of the human fecal pollution signature to the fecal pollution signature in surface waters was generally close to that of sewage, but this ratio decreased dramatically during dry weather and rain events, suggesting that nonhuman fecal pollution was the dominant source during these weather-driven scenarios. The qPCR detection of two human fecal indicators, human Bacteroides and Lachno2, confirmed the urban fecal footprint

  19. 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

  20. A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

    Science.gov (United States)

    Wu, Chia-Chou; Chen, Bor-Sen

    2016-01-01

    Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.

  1. 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.

  2. Politics of coordination in environmental health

    DEFF Research Database (Denmark)

    Holm, Jesper; Kjærgård, Bente; Jelsøe, Erling

    2015-01-01

    on environmental policy integration, for studying the efforts and paradoxes in sector co-ordination, in order to reflect on the pro et cons of integrative approaches to environment and public health. We will give an overview of the various approaches to coordinative efforts from an international to a national...

  3. 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

  4. The Compositional HJ-Biplot-A New Approach to Identifying the Links among Bioactive Compounds of Tomatoes.

    Science.gov (United States)

    Hernández Suárez, Marcos; Molina Pérez, Daniel; Rodríguez-Rodríguez, Elena M; Díaz Romero, Carlos; Espinosa Borreguero, Francisco; Galindo-Villardón, Purificación

    2016-11-02

    Tomatoes have been described as a functional food because of their particular composition of different bioactive compounds. In this study, the proximate composition, minerals and trace elements, and antioxidant compounds were determined in two tomato cultivars (Mariana and Dunkan) that were grown in Gran Canaria (Spain) either conventionally or hydroponically. Although compositional data of this type require being subjected to the specific statistical techniques of compositional analysis, this approach has not usually been considered in this context. In the present case, a compositional Mann-Whitney U test of the data showed significant differences for each factor (cultivar and cultivation system) in several of the compositional variables studied. For the differences between cultivars, these parameters were the protein, Mg, lycopene, ascorbic acid, citric acid, and fumaric acid contents. For the differences between cultivation systems, they were mainly those of the mineral and trace elements group. Although one-year data are insufficient to make clear relationship among compounds because more repetitions in several localities and years are necessary, the compositional HJ-biplot (in which the links provide estimates of the linear relationship among variables) results agreed with other scientific results about linear relationship among some compounds analyzed.

  5. The Compositional HJ-Biplot—A New Approach to Identifying the Links among Bioactive Compounds of Tomatoes

    Directory of Open Access Journals (Sweden)

    Marcos Hernández Suárez

    2016-11-01

    Full Text Available Tomatoes have been described as a functional food because of their particular composition of different bioactive compounds. In this study, the proximate composition, minerals and trace elements, and antioxidant compounds were determined in two tomato cultivars (Mariana and Dunkan that were grown in Gran Canaria (Spain either conventionally or hydroponically. Although compositional data of this type require being subjected to the specific statistical techniques of compositional analysis, this approach has not usually been considered in this context. In the present case, a compositional Mann–Whitney U test of the data showed significant differences for each factor (cultivar and cultivation system in several of the compositional variables studied. For the differences between cultivars, these parameters were the protein, Mg, lycopene, ascorbic acid, citric acid, and fumaric acid contents. For the differences between cultivation systems, they were mainly those of the mineral and trace elements group. Although one-year data are insufficient to make clear relationship among compounds because more repetitions in several localities and years are necessary, the compositional HJ-biplot (in which the links provide estimates of the linear relationship among variables results agreed with other scientific results about linear relationship among some compounds analyzed.

  6. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  7. A New Approach to Identify Optimal Properties of Shunting Elements for Maximum Damping of Structural Vibration Using Piezoelectric Patches

    Science.gov (United States)

    Park, Junhong; Palumbo, Daniel L.

    2004-01-01

    The use of shunted piezoelectric patches in reducing vibration and sound radiation of structures has several advantages over passive viscoelastic elements, e.g., lower weight with increased controllability. The performance of the piezoelectric patches depends on the shunting electronics that are designed to dissipate vibration energy through a resistive element. In past efforts most of the proposed tuning methods were based on modal properties of the structure. In these cases, the tuning applies only to one mode of interest and maximum tuning is limited to invariant points when based on den Hartog's invariant points concept. In this study, a design method based on the wave propagation approach is proposed. Optimal tuning is investigated depending on the dynamic and geometric properties that include effects from boundary conditions and position of the shunted piezoelectric patch relative to the structure. Active filters are proposed as shunting electronics to implement the tuning criteria. The developed tuning methods resulted in superior capabilities in minimizing structural vibration and noise radiation compared to other tuning methods. The tuned circuits are relatively insensitive to changes in modal properties and boundary conditions, and can applied to frequency ranges in which multiple modes have effects.

  8. The Compositional HJ-Biplot—A New Approach to Identifying the Links among Bioactive Compounds of Tomatoes

    Science.gov (United States)

    Hernández Suárez, Marcos; Molina Pérez, Daniel; Rodríguez-Rodríguez, Elena M.; Díaz Romero, Carlos; Espinosa Borreguero, Francisco; Galindo-Villardón, Purificación

    2016-01-01

    Tomatoes have been described as a functional food because of their particular composition of different bioactive compounds. In this study, the proximate composition, minerals and trace elements, and antioxidant compounds were determined in two tomato cultivars (Mariana and Dunkan) that were grown in Gran Canaria (Spain) either conventionally or hydroponically. Although compositional data of this type require being subjected to the specific statistical techniques of compositional analysis, this approach has not usually been considered in this context. In the present case, a compositional Mann–Whitney U test of the data showed significant differences for each factor (cultivar and cultivation system) in several of the compositional variables studied. For the differences between cultivars, these parameters were the protein, Mg, lycopene, ascorbic acid, citric acid, and fumaric acid contents. For the differences between cultivation systems, they were mainly those of the mineral and trace elements group. Although one-year data are insufficient to make clear relationship among compounds because more repetitions in several localities and years are necessary, the compositional HJ-biplot (in which the links provide estimates of the linear relationship among variables) results agreed with other scientific results about linear relationship among some compounds analyzed. PMID:27827839

  9. 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.

  10. 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.

  11. Advice for Coordination

    DEFF Research Database (Denmark)

    Hankin, Chris; Nielson, Flemming; Nielson, Hanne Riis

    2008-01-01

    demanding than the closed joinpoints in more traditional aspect oriented languages like AspectJ. The usefulness of our approach is demonstrated by mechanisms for discretionary and mandatory access control policies, as usually expressed by reference monitors, as well as mechanisms for logging actions.......We show how to extend a coordination language with support for aspect oriented programming. The main challenge is how to properly deal with the trapping of actions before the actual data have been bound to the formal parameters. This necessitates dealing with open joinpoints – which is more...

  12. 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.

  13. A multi-criteria approach to identify favorable areas for goat production systems in Veracruz, México.

    Science.gov (United States)

    Ramírez-Rivera, Emmanuel de Jesús; Lopez-Collado, Jose; Díaz-Rivera, Pablo; Ortega-Jiménez, Eusebio; Torres-Hernández, Glafiro; Jacinto-Padilla, Jazmín; Herman-Lara, Erasmo

    2017-02-09

    This research identifies favorable areas for goat production systems in the state of Veracruz, Mexico. Through the use of the analytic hierarchy process, layers of biophysical and soil information were combined to generate a model of favorability. Model validation was performed by calculating the area under the curve, the true skill statistic, and a qualitative comparison with census records. The results showed the existence of regions with high (4494.3 km(2)) and moderate (2985.8 km(2)) favorability, and these areas correspond to 6.25 and 4.15%, respectively, of the state territory and are located in the regions of Sierra de Huayacocotla, Perote, and Orizaba. These regions are characterized as mountainous and having predominantly temperate-wet or cold climates, and having montane mesophilic forests, containing pine, fir, and desert scrub. The reliability of the distribution model was supported by the area under the curve value (0.96), the true skill statistic (0.86), and consistency with census records.

  14. What's in a Prerequisite? A Mixed-Methods Approach to Identifying the Impact of a Prerequisite Course.

    Science.gov (United States)

    Sato, Brian K; Lee, Amanda K; Alam, Usman; Dang, Jennifer V; Dacanay, Samantha J; Morgado, Pedro; Pirino, Giorgia; Brunner, Jo Ellen; Castillo, Leanne A; Chan, Valerie W; Sandholtz, Judith H

    2017-01-01

    Despite the ubiquity of prerequisites in undergraduate science, technology, engineering, and mathematics curricula, there has been minimal effort to assess their value in a data-driven manner. Using both quantitative and qualitative data, we examined the impact of prerequisites in the context of a microbiology lecture and lab course pairing. Through interviews and an online survey, students highlighted a number of positive attributes of prerequisites, including their role in knowledge acquisition, along with negative impacts, such as perhaps needlessly increasing time to degree and adding to the cost of education. We also identified a number of reasons why individuals do or do not enroll in prerequisite courses, many of which were not related to student learning. In our particular curriculum, students did not believe the microbiology lecture course impacted success in the lab, which agrees with our analysis of lab course performance using a previously established "familiarity" scale. These conclusions highlight the importance of soliciting and analyzing student feedback, and triangulating these data with quantitative performance metrics to assess the state of science, technology, engineering, and mathematics curricula.

  15. What’s in a Prerequisite? A Mixed-Methods Approach to Identifying the Impact of a Prerequisite Course

    Science.gov (United States)

    Sato, Brian K.; Lee, Amanda K.; Alam, Usman; Dang, Jennifer V.; Dacanay, Samantha J.; Morgado, Pedro; Pirino, Giorgia; Brunner, Jo Ellen; Castillo, Leanne A.; Chan, Valerie W.; Sandholtz, Judith H.

    2017-01-01

    Despite the ubiquity of prerequisites in undergraduate science, technology, engineering, and mathematics curricula, there has been minimal effort to assess their value in a data-driven manner. Using both quantitative and qualitative data, we examined the impact of prerequisites in the context of a microbiology lecture and lab course pairing. Through interviews and an online survey, students highlighted a number of positive attributes of prerequisites, including their role in knowledge acquisition, along with negative impacts, such as perhaps needlessly increasing time to degree and adding to the cost of education. We also identified a number of reasons why individuals do or do not enroll in prerequisite courses, many of which were not related to student learning. In our particular curriculum, students did not believe the microbiology lecture course impacted success in the lab, which agrees with our analysis of lab course performance using a previously established “familiarity” scale. These conclusions highlight the importance of soliciting and analyzing student feedback, and triangulating these data with quantitative performance metrics to assess the state of science, technology, engineering, and mathematics curricula. PMID:28232587

  16. A Cost Benefit Analysis Approach to Identify Improvements in Merchant Navy Deck Officers’ HELM (Human Element Leadership and Management Training

    Directory of Open Access Journals (Sweden)

    Farhan Saeed

    2016-12-01

    Full Text Available A review of maritime accidents conducted over the last decade confirms that human error is the main contributing factor in these incidents. Well-developed Non-Technical Skills (NTS can reduce the effects of human error. NTS include both interpersonal and cognitive skills such as situation awareness, teamwork, decision-making, leadership, managerial skills, communication and language skills. In a crisis situation good NTS allow a deck officer to recognise the problem quickly, take action to manage the situation, and utilise the available team members safely and effectively. This paper identifies the importance of NTS training for merchant navy deck officers. It also highlights room for improvement in the existing HELM training. Research has shown that at present the structure of HELM training is not very effective. The other safety critical domains’ efforts into NTS developments are investigated and examples of best practice are adapted into the maritime domain’s NTS training. Suggestions are given for improvements to the HELM course based on proven successful methods in other safety critical domains (aviation and anaesthesia. A subsequent Cost Benefit Analysis for improving deck officers’ NTS is also carried out through the use of Bayesian Networks and Decision Tree Modelling.

  17. 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 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 disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings.

  18. A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients

    Directory of Open Access Journals (Sweden)

    Fardin Paolo

    2010-07-01

    Full Text Available Abstract Background Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. Results We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Conclusions Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. A combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancer.

    Science.gov (United States)

    Li, Ning; Kaur, Sippy; Greshock, Joel; Lassus, Heini; Zhong, Xiaomin; Wang, Yanling; Leminen, Arto; Shao, Zhongjun; Hu, Xiaowen; Liang, Shun; Katsaros, Dionyssios; Huang, Qihong; Bützow, Ralf; Weber, Barbara L; Coukos, George; Zhang, Lin

    2012-01-01

    Oncomirs are microRNAs (miRNA) that acts as oncogenes or tumor suppressor genes. Efficient identification of oncomirs remains a challenge. Here we report a novel, clinically guided genetic screening approach for the identification of oncomirs, identifying mir-30d through this strategy. mir-30d regulates tumor cell proliferation, apoptosis, senescence, and migration. The chromosomal locus harboring mir-30d was amplified in more than 30% of multiple types of human solid tumors (n = 1,283). Importantly, higher levels of mir-30d expression were associated significantly with poor clinical outcomes in ovarian cancer patients (n = 330, P = 0.0016). Mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase CASP3. The guided genetic screening approach validated by this study offers a powerful tool to identify oncomirs that may have utility as biomarkers or targets for drug development.

  4. 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.

  5. Isolation and characterization of quinine from Polygonatum verticillatum: A new marker approach to identify substitution and adulteration

    Directory of Open Access Journals (Sweden)

    Jaswinder Kaur Virk

    2016-01-01

    Full Text Available Polygonatum verticillatum (Mahameda is an important ingredient of Ashtawarga and Ayurvedic formulations. Nowadays, it comes under the category of endangered plants due to large scale and indiscriminate collection of wild material. To overcome the scarcity, substitutes of Mahameda are also commonly used in market. These additives are different from the authentic plant by Ayurvedic and pharmacological theory of drug action, thereby resulting in substitution/adulteration. Substitution is a critical issue in isolation and quantification of the therapeutically active ingredients that can be used as markers in the identification of substitution/adulteration. Methanolic extract of the rhizomes of P. verticillatum was subjected to preliminary phytochemical screening for the detection of phytoconstituents, followed by column chromatography for isolation of the marker. The column was first eluted with pure hexane, and polarity of the solvent was gradually increased. A total of 1180 fractions were collected and pooled on the basis of thin-layer chromatography profile. The single compound was isolated and confirmed by chemical test, melting point, spectral analysis, and comparison with literature. Phytochemical screening of the extract shows the presence of alkaloids, flavonoids, carbohydrates, terpenoids, and phenolics. A pure white crystalline powder was isolated by column chromatography which was characterized as (6-methoxyquinolin-4-yl-8-vinylquinuclidin-2-yl methanol, i.e. Quinine. The isolated compound, Quinine, was identified as a novel compound in Mahameda as it has not been reported in the genus Polygonatum, till now. It can be used as a marker for the identification of substitution/adulteration and standardization of P. verticillatum.

  6. A multicomponent approach to identify predictors of hospital outcomes in older in-patients: a multicentre, observational study.

    Directory of Open Access Journals (Sweden)

    Stefanie L De Buyser

    Full Text Available BACKGROUND: The identification of older patients at risk of poor hospital outcomes (e.g. longer hospital stay, in-hospital mortality, and institutionalisation is important to provide an effective healthcare service. OBJECTIVE: To identify factors related to older patients' clinical, nutritional, functional and socio-demographic profiles at admission to an acute care ward that can predict poor hospital outcomes. DESIGN AND SETTING: The CRiteria to assess appropriate Medication use among Elderly complex patients project was a multicentre, observational study performed in geriatric and internal medicine acute care wards of seven Italian hospitals. SUBJECTS: One thousand one hundred twenty-three consecutively admitted patients aged 65 years or older. METHODS: Hospital outcomes were length of stay, in-hospital mortality, and institutionalisation. RESULTS: Mean age of participants was 81 years, 56% were women. Median length of stay was 10 (7-14 days, 41 patients died during hospital stay and 37 were newly institutionalised. Number of drugs before admission, metastasized cancer, renal failure or dialysis, infection, falls at home during the last year, pain, and walking speed were independent predictors of LoS. Total dependency in activities of daily living and inability to perform grip strength test were independent predictors of in-hospital mortality. Malnutrition and total dependency in activities of daily living were independent predictors of institutionalisation. CONCLUSIONS: Our results confirm that not only diseases, but also multifaceted aspects of ageing such as physical function and malnutrition are strong predictors of hospital outcomes and suggest that these variables should be systematically recorded.

  7. Metabolic footprinting: a new approach to identify physiological changes in complex microbial communities upon exposure to toxic chemicals.

    Science.gov (United States)

    Henriques, Inês D S; Aga, Diana S; Mendes, Pedro; O'Connor, Seamus K; Love, Nancy G

    2007-06-01

    Metabolic footprinting coupled with statistical analysis was applied to multiple, chemically stressed activated sludge cultures to identify probable biomarkers that indicate community stress. The impact of cadmium (Cd), 2,4-dinitrophenol (DNP), and N-ethyl-maleimide (NEM) shock loads on the composition of the soluble fraction of activated sludge cultures was analyzed by gross biomolecular analyses and liquid chromatography-mass spectrometry (LC-MS). Fresh mixed liquor from four distinct treatment plants was each divided in four different batches and was subjected to no chemical addition (control) and spike additions of the stressors Cd, DNP, or NEM. The results indicate that chemical stress caused a significant release of proteins, carbohydrates, and humic acids from the floc structure into the bulk liquid. Using discriminant function analysis (DFA) with genetic algorithm variable selection (GA-DFA), the samples subjected to the different stress conditions plus control could be differentiated, thereby indicating that the footprints of the soluble phase generated by LC-MS were different for the four conditions tested and, therefore, were toxin-specific but community-independent. These footprints, thus, contain information about specific biomolecular differences between the stressed samples, and we found that only a limited number of m/z (mass to charge) ratios from the mass spectra were needed to differentiate between the control and each stressed sample. Since the experiments were conducted with mixed liquor from four distinct wastewater treatment plants, the discriminant m/z ratios may potentially be used as universal stress biomarkers in activated sludge systems.

  8. Isolation and characterization of quinine from Polygonatum verticillatum: A new marker approach to identify substitution and adulteration

    Science.gov (United States)

    Virk, Jaswinder Kaur; Kumar, Sanjiv; Singh, Ranjit; Tripathi, Avinash C.; Saraf, Shailendra K.; Gupta, Vikas; Bansal, Parveen

    2016-01-01

    Polygonatum verticillatum (Mahameda) is an important ingredient of Ashtawarga and Ayurvedic formulations. Nowadays, it comes under the category of endangered plants due to large scale and indiscriminate collection of wild material. To overcome the scarcity, substitutes of Mahameda are also commonly used in market. These additives are different from the authentic plant by Ayurvedic and pharmacological theory of drug action, thereby resulting in substitution/adulteration. Substitution is a critical issue in isolation and quantification of the therapeutically active ingredients that can be used as markers in the identification of substitution/adulteration. Methanolic extract of the rhizomes of P. verticillatum was subjected to preliminary phytochemical screening for the detection of phytoconstituents, followed by column chromatography for isolation of the marker. The column was first eluted with pure hexane, and polarity of the solvent was gradually increased. A total of 1180 fractions were collected and pooled on the basis of thin-layer chromatography profile. The single compound was isolated and confirmed by chemical test, melting point, spectral analysis, and comparison with literature. Phytochemical screening of the extract shows the presence of alkaloids, flavonoids, carbohydrates, terpenoids, and phenolics. A pure white crystalline powder was isolated by column chromatography which was characterized as (6-methoxyquinolin-4-yl-8-vinylquinuclidin-2-yl) methanol, i.e. Quinine. The isolated compound, Quinine, was identified as a novel compound in Mahameda as it has not been reported in the genus Polygonatum, till now. It can be used as a marker for the identification of substitution/adulteration and standardization of P. verticillatum. PMID:27833896

  9. 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...

  10. 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...

  11. 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...

  12. 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

  13. 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

  14. 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...

  15. Divergent Urinary Metabolic Phenotypes between Major Depressive Disorder and Bipolar Disorder Identified by a Combined GC-MS and NMR Spectroscopic Metabonomic Approach.

    Science.gov (United States)

    Chen, Jian-Jun; Zhou, Chan-Juan; Liu, Zhao; Fu, Yu-Ying; Zheng, Peng; Yang, De-Yu; Li, Qi; Mu, Jun; Wei, You-Dong; Zhou, Jing-Jing; Huang, Hua; Xie, Peng

    2015-08-07

    Bipolar disorder (BD) is a complex debilitating mental disorder that is often misdiagnosed as major depressive disorder (MDD). Therefore, a large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice. To address this challenge, objective laboratory-based tests are needed to discriminate BD from MDD patients. Here, a combined gas chromatography-mass spectrometry (GC-MS)-based and nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was performed to profile urine samples from 76 MDD and 43 BD subjects (training set) to identify the differential metabolites. Samples from 126 healthy controls were included as metabolic controls. A candidate biomarker panel was identified by further analyzing these differential metabolites. A testing set of, 50 MDD and 28 BD subjects was then used to independently validate the diagnostic efficacy of the identified panel using an area under the receiver operating characteristic curve (AUC). A total of 20 differential metabolites responsible for the discrimination between MDD and BD subjects were identified. A panel consisting of six candidate urinary metabolite biomarkers (propionate, formate, (R*,S*)2,3-dihydroxybutanoic acid, 2,4-dihydroxypyrimidine, phenylalanine, and β-alanine) was identified. This panel could distinguish BD from MDD subjects with an AUC of 0.913 and 0.896 in the training and testing sets, respectively. These results reveal divergent urinary metabolic phenotypes between MDD and BD. The identified urinary biomarkers can aid in the future development of an objective laboratory-based diagnostic test for distinguishing BD from MDD patients.

  16. 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.

  17. 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.

  18. Limitations of Radar Coordinates

    OpenAIRE

    Bini, Donato; Lusanna, Luca; Mashhoon, Bahram

    2004-01-01

    The construction of a radar coordinate system about the world line of an observer is discussed. Radar coordinates for a hyperbolic observer as well as a uniformly rotating observer are described in detail. The utility of the notion of radar distance and the admissibility of radar coordinates are investigated. Our results provide a critical assessment of the physical significance of radar coordinates.

  19. 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.

  20. The interprocess NIR sampling as an alternative approach to multivariate statistical process control for identifying sources of product-quality variability.

    Science.gov (United States)

    Marković, Snežana; Kerč, Janez; Horvat, Matej

    2017-03-01

    We are presenting a new approach of identifying sources of variability within a manufacturing process by NIR measurements of samples of intermediate material after each consecutive unit operation (interprocess NIR sampling technique). In addition, we summarize the development of a multivariate statistical process control (MSPC) model for the production of enteric-coated pellet product of the proton-pump inhibitor class. By developing provisional NIR calibration models, the identification of critical process points yields comparable results to the established MSPC modeling procedure. Both approaches are shown to lead to the same conclusion, identifying parameters of extrusion/spheronization and characteristics of lactose that have the greatest influence on the end-product's enteric coating performance. The proposed approach enables quicker and easier identification of variability sources during manufacturing process, especially in cases when historical process data is not straightforwardly available. In the presented case the changes of lactose characteristics are influencing the performance of the extrusion/spheronization process step. The pellet cores produced by using one (considered as less suitable) lactose source were on average larger and more fragile, leading to consequent breakage of the cores during subsequent fluid bed operations. These results were confirmed by additional experimental analyses illuminating the underlying mechanism of fracture of oblong pellets during the pellet coating process leading to compromised film coating.

  1. 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.

  2. 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.

  3. Identifying mangrove species and their surrounding land use and land cover classes using object-oriented approach with a lacunarity spatial measure

    Science.gov (United States)

    Myint, S.W.; Giri, C.P.; Wang, L.; Zhu, Z.; Gillete, S.C.

    2008-01-01

    Accurate and reliable information on the spatial distribution of mangrove species is needed for a wide variety of applications, including sustainable management of mangrove forests, conservation and reserve planning, ecological and biogeographical studies, and invasive species management. Remotely sensed data have been used for such purposes with mixed results. Our study employed an object-oriented approach with the use of a lacunarity technique to identify different mangrove species and their surrounding land use and land cover classes in a tsunami-affected area of Thailand using Landsat satellite data. Our results showed that the object-oriented approach with lacunarity-transformed bands is more accurate (over-all accuracy 94.2%; kappa coefficient = 0.91) than traditional per-pixel classifiers (overall accuracy 62.8%; and kappa coefficient = 0.57). Copyright ?? 2008 by Bellwether Publishing, Ltd. All rights reserved.

  4. A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

    Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

  5. Novel Coordination Chemistry of Aluminum Borohydride

    Science.gov (United States)

    2014-08-01

    four different crystal shapes were identified under a microscope.  Super thin plates are not a preferred crystal shape for X-ray analysis. Anion ...coordination of various ligands. Previously we investigated an IL based upon the [Al(BH4)4]- anion . This material showed a much improved air and...moisture stability compared to ABH. Here we present research on the coordination of the cyanoborohydride anion (NCBH3-) with ABH. The coordination

  6. A New Approach to Non-Coordinating Anions: Lewis Acid Enhancement of Porphyrin Metal Centers in a Zwitterionic Metal$-$Organic Framework

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jacob A. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Petersen, Brenna M. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Kormos, Attila [Hungarian Academy of Sciences, Budapest (Hungary); Echeverría, Elena [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Physics and Astronomy; Chen, Yu-Sheng [Univ. of Chicago, Argonne, IL (United States). ChemMatCARS, Center for Advanced Radiation Sources; Zhang, Jian [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry

    2017-02-28

    Here, we describe a new strategy to generate non-coordinating anions using zwitterionic metal–organic frameworks (MOFs). By assembly of anionic inorganic secondary building blocks (SBUs) ([In(CO2)4]$-$) with cationic metalloporphyrin-based organic linkers, we prepared zwitterionic MOFs in which the complete internal charge separation effectively prevents the potential binding of the counteranion to the cationic metal center. We demonstrate the enhanced Lewis acidity of MnIII- and FeIII-porphyrins in the zwitterionic MOFs in three representative electrocyclization reactions: [2 + 1] cycloisomerization of enynes, [3 + 2] cycloaddition of aziridines and alkenes, and [4 + 2] hetero-Diels–Alder cycloaddition of aldehydes with dienes. Lastly, this work paves a new way to design functional MOFs for tunable chemical catalysis.

  7. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C; Maletta, Raffaele G; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-10-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10(-7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

  8. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C.; Maletta, Raffaele G.; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A.; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-01-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10−7 and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of –cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD–genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis. PMID:26154020

  9. 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

  10. 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

  11. 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

  12. Towards Identifying Current Strategies and Innovative Approaches for the Growth of Dairy Goat Entrepreneurs: A Case Study of Njiru District, Kenya

    Directory of Open Access Journals (Sweden)

    Philemon Lagat

    2012-10-01

    Full Text Available Dairy goats remain to be the most lucrative business where land fragmentation has resulted in the formation of small pieces of land that cannot support dairy cattle farming (Kinyanjui et al., 2008. From casual observation, this situation does not prevail in Njiru District since the growth is very slow hence the venture is risky. Nevertheless, some few farmers have risked by taking the initiative of venturing into the business so as to seize the opportunity. The purpose of this study was to identify current strategies and innovative approaches for the growth of dairy goat entrepreneurs.The population of this study was determined by getting a list of farmers engaged in micro and small dairy goat enterprises. This constituted the sampling frame. Simple random sampling method was used to select 36 dairy goat farmers from a list of dairy goat enterprises in Njiru District. The questionnaire comprised of closed and open ended questions. Descriptive statistics was used to collect data and included frequency tables. Further, a computer statistical package for social sciences (SPSS was used in entering and analyzing the data. The study established that the entrepreneurs adopted innovative approaches in their businesses. All of the respondents claimed that their businesses had increased in growth as a result of adopting current strategies and innovative approaches in their dairy goat enterprises.

  13. Coordination and Cooperation

    OpenAIRE

    Janssen, Maarten

    2003-01-01

    textabstractThis comment makes four related points. First, explaining coordination is different from explaining cooperation. Second, solving the coordination problem is more important for the theory of games than solving the cooperation problem. Third, a version of the Principle of Coordination can be rationalized on individualistic grounds. Finally, psychological game theory should consider how players perceive their gaming situation. ---------------------------------------------------------...

  14. 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…

  15. Coordination and Cooperation

    NARCIS (Netherlands)

    M.C.W. Janssen (Maarten)

    2003-01-01

    textabstractThis comment makes four related points. First, explaining coordination is different from explaining cooperation. Second, solving the coordination problem is more important for the theory of games than solving the cooperation problem. Third, a version of the Principle of Coordination can

  16. 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.

  17. 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.

  18. 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.

  19. 基于 BP神经网络的录音地点识别方法%An Approach to Identifying Rceording Locations Based on BP Neural Networks

    Institute of Scientific and Technical Information of China (English)

    王学强; 吉建梅; 包永强

    2014-01-01

    The existing digital audio forensics technology has difficulty in identifying the location,where the recordings are made,making it hard for judicial organs to assess the effectiveness of the audio evidence.To address such an issue,this paper devises a method for identifying such locations using a grid ENF based on BP neural network. In the identification process ,grid ENF is used as a training sample for purpose of training BP neural network.Next,the grid frequency data are extracted from audio files as input samples,which are then identified by using the trained BP neural network.Finally,to identify the location of the recording,optimal recognition results are obtained from the recognition results by adopting a simulated annealing algorithm.The experimental results show that recognition rate of this approach is at least 90.6 %,and the approach is reasonably reliable.%现有的数字音频取证技术很难做到录音地点的识别,因此司法机关就不易对音频证据的有效性做出判断.针对现状,本文设计了一种基于BP神经网络的录音地点识别方法.该方法是将电网频率( ENF)作为识别根据.进行地点识别操作时,首先将电网ENF作为训练样本训练BP神经网络,然后从待取证的音频文件中提取电网频率数据并作为输入样本,用训练好的BP神经网络对输入样本进行识别,最后用模拟退火算法从识别结果中搜索出最佳识别结果,从而识别出录音的地点.实验结果表明,该方法的识别准确率最低达到90.6%,可靠性满足一定的要求.

  20. A systematic SNP selection approach to identify mechanisms underlying disease aetiology: linking height to post-menopausal breast and colorectal cancer risk

    Science.gov (United States)

    Elands, Rachel J. J.; Simons, Colinda C. J. M.; Riemenschneider, Mona; Isaacs, Aaron; Schouten, Leo J.; Verhage, Bas A.; Van Steen, Kristel; Godschalk, Roger W. L.; van den Brandt, Piet A.; Stoll, Monika; Weijenberg, Matty P.

    2017-01-01

    Data from GWAS suggest that SNPs associated with complex diseases or traits tend to co-segregate in regions of low recombination, harbouring functionally linked gene clusters. This phenomenon allows for selecting a limited number of SNPs from GWAS repositories for large-scale studies investigating shared mechanisms between diseases. For example, we were interested in shared mechanisms between adult-attained height and post-menopausal breast cancer (BC) and colorectal cancer (CRC) risk, because height is a risk factor for these cancers, though likely not a causal factor. Using SNPs from public GWAS repositories at p-values cancer site-specific pathways. This systematic approach identified a limited number of clustered SNPs, which pinpoint potential shared mechanisms linking together the complex phenotypes height, post-menopausal BC and CRC. PMID:28117334

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Multiobjective Coordination Approach in Concurrent Engineering%并行工程中面向多目标的目标决策方案

    Institute of Scientific and Technical Information of China (English)

    吕常魁; 姜澄宇; 王宁生

    2001-01-01

    目标决策(Goal programming,GP)是一种常用的多目标分析管理技术。在实施并行工程(C0ncurrent en-gineering,CE)期间结合目标决策技术能够很好地协调工程中多个目标间的冲突。如何压缩产品开发时间和降低耗费一直是生产中决策者关心的问题。文中采用目标决策的方法,引入了GP/CE数学模型,针对产品并行开发中耗资与耗时两个相冲突的目标,对产品并行开发的过程进行GP/CE模型建模,达到优化并行工程的实施效果。%How to balance and coordinate different conflicting objects in concurrent engineering (CE) has long been a disturbance in manufacturing industry.Goal programming (GP) is a commonly used engineering and management technique to improve decision making by conflicting objectives criteria.The conflicting objectives can be harmonized when using GP as an aid to CE in new product development.In the practical situation,reducing both cost and time tolerance has always been an interesting area for the decision maker.This paper shows how to construct GP/CE model using GP technology in CE process according to the double conflicting objectives——cost and time,to enhance the performance of CE.A simple and effective methodology algorithm for the problem is presented to generate efficient solutions with respect to cost and time.

  7. The benefits of using a mixed methods approach--quantitative with qualitative--to identify client satisfaction and unmet needs in an HIV healthcare centre.

    Science.gov (United States)

    Chow, M Y K; Quine, S; Li, M

    2010-04-01

    Research into patient satisfaction with HIV ambulatory healthcare facilities is limited due to confidentiality restraints, the short history of the condition and the stigma attached. Furthermore, most satisfaction studies of this client group have not used mixed methods (quantitative with qualitative) despite its increasing use since the 1990s in healthcare research. This cross-sectional study demonstrates how a mixed methods approach is beneficial in assessing HIV client satisfaction and in identifying unmet needs in HIV healthcare. Conducted at the largest ambulatory HIV healthcare centre in Australia, this study consisted of two phases conducted sequentially: Phase One, a quantitative self-administered questionnaire survey, provided an overall statistical picture of satisfaction levels. This was followed by Phase Two, qualitative semi-structured face-to-face interviews, which enabled in-depth investigation of the reasons for satisfaction/dissatisfaction. Phase One had 166 respondents, giving a high response rate of 71%, while Phase Two had 22 participants. The study demonstrates the three advantages of using a mixed methods approach. Firstly, it increased the comprehensiveness of overall findings, by showing how qualitative data (Phase Two) provided explanations for statistical data (Phase One). Secondly, it expanded the dimensions of the research topic, as Phase Two enabled investigation of the determinants of satisfaction/dissatisfaction more broadly after assessing the client satisfaction levels in Phase One. Thirdly, it increased the methodological rigour as findings in both phases could be checked for consistency. Thus using a mixed methods approach can greatly enhance our understanding of client satisfaction in HIV/AIDS research.

  8. 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.

  9. 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.

  10. 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.

  11. 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)

  12. 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 sin