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Sample records for factor governing multiple

  1. Decomposition of the factors that govern binding site preference in a multiple rotaxane.

    PubMed

    Angelo, Joseph P; Sohlberg, Karl

    2009-06-18

    A particularly interesting class of multiple rotaxanes consists of complexes where one long shaft threads two rings. If the shaft contains three or more potential binding sites for the rings, multiple co-conformations are possible. Such a complex is a molecular topological analogue to an abacus. Here we address the question, how does strength of ring binding to the shaft vary with respect to position on the shaft? Previous studies have found that a shaft with three binding sites exhibits strongest ring binding at the center site. Here a five-binding-site shaft is studied. We employ a novel method to partition the total energy of the system into contributions from intercomponent binding and intracomponent distortion. The method uses the output of quantum mechanical electronic structure calculations to determine fitting parameters in a set of coupled equations. The solution of the equations yields the energy partitioning and reveals the influence of long-range intercomponent interactions.

  2. Government Information Access: A decisive Factor for E-Government

    NASA Astrophysics Data System (ADS)

    Xia, Yikun; Huang, Cui

    In recent years we are witnessing enormous development of e-government, which has brought about great changes in our society. This study examines the relationship between the levels of e-government and the quality of government information access, pointing out that e-government principles are based on the assumption that government information should be accessed among all kinds of organizations. In contrast to government webs' rapid growth, the low quality of government information access has been a dilemma which impacts the usability and efficiency of e-government. This paper also analyzes blocking factors about information access in China, draw a conclusion that on-line government information access should be the key factor of e-government which steps should be taken to enhance accessibility to government information.

  3. Multiple-camera tracking: UK government requirements

    NASA Astrophysics Data System (ADS)

    Hosmer, Paul

    2007-10-01

    The Imagery Library for Intelligent Detection Systems (i-LIDS) is the UK government's new standard for Video Based Detection Systems (VBDS). The standard was launched in November 2006 and evaluations against it began in July 2007. With the first four i-LIDS scenarios completed, the Home Office Scientific development Branch (HOSDB) are looking toward the future of intelligent vision in the security surveillance market by adding a fifth scenario to the standard. The fifth i-LIDS scenario will concentrate on the development, testing and evaluation of systems for the tracking of people across multiple cameras. HOSDB and the Centre for the Protection of National Infrastructure (CPNI) identified a requirement to track targets across a network of CCTV cameras using both live and post event imagery. The Detection and Vision Systems group at HOSDB were asked to determine the current state of the market and develop an in-depth Operational Requirement (OR) based on government end user requirements. Using this OR the i-LIDS team will develop a full i-LIDS scenario to aid the machine vision community in its development of multi-camera tracking systems. By defining a requirement for multi-camera tracking and building this into the i-LIDS standard the UK government will provide a widely available tool that developers can use to help them turn theory and conceptual demonstrators into front line application. This paper will briefly describe the i-LIDS project and then detail the work conducted in building the new tracking aspect of the standard.

  4. Sequence Factorization with Multiple References

    PubMed Central

    Wandelt, Sebastian; Leser, Ulf

    2015-01-01

    The success of high-throughput sequencing has lead to an increasing number of projects which sequence large populations of a species. Storage and analysis of sequence data is a key challenge in these projects, because of the sheer size of the datasets. Compression is one simple technology to deal with this challenge. Referential factorization and compression schemes, which store only the differences between input sequence and a reference sequence, gained lots of interest in this field. Highly-similar sequences, e.g., Human genomes, can be compressed with a compression ratio of 1,000:1 and more, up to two orders of magnitude better than with standard compression techniques. Recently, it was shown that the compression against multiple references from the same species can boost the compression ratio up to 4,000:1. However, a detailed analysis of using multiple references is lacking, e.g., for main memory consumption and optimality. In this paper, we describe one key technique for the referential compression against multiple references: The factorization of sequences. Based on the notion of an optimal factorization, we propose optimization heuristics and identify parameter settings which greatly influence 1) the size of the factorization, 2) the time for factorization, and 3) the required amount of main memory. We evaluate a total of 30 setups with a varying number of references on data from three different species. Our results show a wide range of factorization sizes (optimal to an overhead of up to 300%), factorization speed (0.01 MB/s to more than 600 MB/s), and main memory usage (few dozen MB to dozens of GB). Based on our evaluation, we identify the best configurations for common use cases. Our evaluation shows that multi-reference factorization is much better than single-reference factorization. PMID:26422374

  5. Multiple factors drive regional agricultural abandonment.

    PubMed

    Osawa, Takeshi; Kohyama, Kazunori; Mitsuhashi, Hiromune

    2016-01-15

    An understanding of land-use change and its drivers in agroecosystems is important when developing adaptations to future environmental and socioeconomic pressures. Agricultural abandonment occurs worldwide with multiple potentially positive and negative consequences; however, the main factors causing agricultural abandonment in a country i.e., at the macro scale, have not been identified. We hypothesized that socio-environmental factors driving agricultural abandonment could be summarized comprehensively into two, namely "natural" and "social", and the relative importance of these differs among regions. To test this postulate, we analyzed the factors currently leading to agricultural abandonment considering ten natural environment variables (e.g., temperature) and five social variables (e.g., number of farmers) using the random forest machine learning method after dividing Japan into eight regions. Our results showed that agricultural abandonment was driven by various socio-environmental factors, and the main factors leading to agricultural abandonment differed among regions, especially in Hokkaido in northern Japan. Hokkaido has a relatively large area of concentrated farmland, and abandonment might have resulted from the effectiveness of cultivation under specific climate factors, whereas the other regions have relatively small areas of farmland with many elderly part-time farmers. In such regions, abandonment might have been caused by the decreasing numbers of potential farmers. Thus, two different drivers of agricultural abandonment were found: inefficient cultivation and decreasing numbers of farmers. Therefore, agricultural abandonment cannot be prevented by adopting a single method or policy. Agricultural abandonment is a significant problem not only for food production but also for several ecosystem services. Governments and decision-makers should develop effective strategies to prevent further abandonment to ensure sustainable future management of agro-ecosystems.

  6. Multiple factors drive regional agricultural abandonment.

    PubMed

    Osawa, Takeshi; Kohyama, Kazunori; Mitsuhashi, Hiromune

    2016-01-15

    An understanding of land-use change and its drivers in agroecosystems is important when developing adaptations to future environmental and socioeconomic pressures. Agricultural abandonment occurs worldwide with multiple potentially positive and negative consequences; however, the main factors causing agricultural abandonment in a country i.e., at the macro scale, have not been identified. We hypothesized that socio-environmental factors driving agricultural abandonment could be summarized comprehensively into two, namely "natural" and "social", and the relative importance of these differs among regions. To test this postulate, we analyzed the factors currently leading to agricultural abandonment considering ten natural environment variables (e.g., temperature) and five social variables (e.g., number of farmers) using the random forest machine learning method after dividing Japan into eight regions. Our results showed that agricultural abandonment was driven by various socio-environmental factors, and the main factors leading to agricultural abandonment differed among regions, especially in Hokkaido in northern Japan. Hokkaido has a relatively large area of concentrated farmland, and abandonment might have resulted from the effectiveness of cultivation under specific climate factors, whereas the other regions have relatively small areas of farmland with many elderly part-time farmers. In such regions, abandonment might have been caused by the decreasing numbers of potential farmers. Thus, two different drivers of agricultural abandonment were found: inefficient cultivation and decreasing numbers of farmers. Therefore, agricultural abandonment cannot be prevented by adopting a single method or policy. Agricultural abandonment is a significant problem not only for food production but also for several ecosystem services. Governments and decision-makers should develop effective strategies to prevent further abandonment to ensure sustainable future management of agro

  7. GEOCHEMICAL FACTORS GOVERNING METHYL MERCURY PRODUCTION IN MERCURY CONTAMINATED SEDIMENTS

    EPA Science Inventory

    Bench scale experiments were conducted to improve our understanding of aquatic mercury transformation processes (biotic and abiotic), specifically those factors which govern the production of methyl mercury (MeHg) in sedimentary environments. The greatest cause for concern regar...

  8. Factors Governing Pasting Properties of Waxy Wheat Flours

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To realize the full potential of waxy wheat, the pasting properties of hard waxy wheat flours as well as factors governing the pasting properties were investigated and compared with normal and partial waxy wheat flours. Starches isolated from six hard waxy wheat flours had similar pasting properties...

  9. Molecular Specificity of Multiple Hippocampal Processes Governing Fear Extinction

    PubMed Central

    Radulovic, Jelena; Tronson, Natalie C.

    2010-01-01

    have stimulate-d intense research in this area. Rodent studies identified the circuits involved in the conditioning and extinction of fear of salient cues 99,98,85,93,150, generating data that were confirmed in humans with brain imaging approaches 114,130. Nevertheless, research with experimental animals has not fully taken advantage of human data in order to better interpret extinction mechanisms in the framework of learning, expectation and emotion governing fear-motivated behavior. The present article aims to summarize recent molecular evidence on fear extinction, focusing on hippocampal mechanisms and experimental models of contextual fear, and compare the results with other relevant fear paradigms and human imaging studies. Instead of conceptualizing extinction learning as one process, such as CS-noUS association or inhibitory learning 19,26,96, we propose that fear extinction reflects the behavioral output of several region-specific learning processes that modify different components of the conditioning memory. The significance of these findings is discussed in the framework of fear regulation and anxiety disorders. PMID:20458884

  10. Mapping of government land encroachment in Cameron Highlands using multiple remote sensing datasets

    NASA Astrophysics Data System (ADS)

    Zin, M. H. M.; Ahmad, B.

    2014-02-01

    The cold and refreshing highland weather is one of the factors that give impact to socio-economic growth in Cameron Highlands. This unique weather of the highland surrounded by tropical rain forest can only be found in a few places in Malaysia. It makes this place a famous tourism attraction and also provides a very suitable temperature for agriculture activities. Thus it makes agriculture such as tea plantation, vegetable, fruits and flowers one of the biggest economic activities in Cameron Highlands. However unauthorized agriculture activities are rampant. The government land, mostly forest area have been encroached by farmers, in many cases indiscriminately cutting down trees and hill slopes. This study is meant to detect and assess this encroachment using multiple remote sensing datasets. The datasets were used together with cadastral parcel data where survey lines describe property boundary, pieces of land are subdivided into lots of government and private. The general maximum likelihood classification method was used on remote sensing image to classify the land-cover in the study area. Ground truth data from field observation were used to assess the accuracy of the classification. Cadastral parcel data was overlaid on the classification map in order to detect the encroachment area. The result of this study shows that there is a land cover change of 93.535 ha in the government land of the study area between years 2001 to 2010, nevertheless almost no encroachment took place in the studied forest reserve area. The result of this study will be useful for the authority in monitoring and managing the forest.

  11. Prognostic factors and classification in multiple myeloma.

    PubMed Central

    San Miguel, J. F.; Sànchez, J.; Gonzalez, M.

    1989-01-01

    Analyses of prognostic factors have allowed the design of staging systems in different haematological disorders. In a series of 220 patients with multiple myeloma, univariate analysis showed that nine parameters had a significant adverse effect on survival; poor performance status (Karnowsky scaling system less than 70%), infections before diagnosis, renal impairment (assessed either by creatinine clearance greater than 2 mg dl-1 or urea greater than 40 mg dl-1), serum calcium (greater than 10 mg dl-1), severe anaemia (less than 8.5 g dl-1), the presence of Bence-Jones proteinuria, failure to achieve complete remission, more than 40% plasma cells in bone marrow and a low paraprotein index (monoclonal component/% plasma cells: P less than 0.09). In addition, this index correlated significantly with all the other prognostic factors except performance status. The best combination of disease characteristics selected by means of the Cox regression proportional hazards method were performance status and creatinine levels. Additionally, by factor analysis of principal components we obtained a regression equation that included creatinine levels, haemoglobin, performance status and paraprotein index. Using this it was possible to separate the series of patients into three risk categories: A (65 patients), B (69 patients) and C (65 patients) with a median survival of 41, 24 and 12 months, respectively. The model provided similar results to those of the British Medical Research Council, whereas the staging systems proposed by Durie and Salmon, Merlin et al. and Carbone et al. had a lower discriminant value in our series. PMID:2757917

  12. A Multiple-Item Scale for Assessing E-Government Service Quality

    NASA Astrophysics Data System (ADS)

    Papadomichelaki, Xenia; Mentzas, Gregoris

    A critical element in the evolution of e-governmental services is the development of sites that better serve the citizens’ needs. To deliver superior service quality, we must first understand how citizens perceive and evaluate online citizen service. This involves defining what e-government service quality is, identifying its underlying dimensions, and determining how it can be conceptualized and measured. In this article we conceptualise an e-government service quality model (e-GovQual) and then we develop, refine, validate, confirm and test a multiple-item scale for measuring e-government service quality for public administration sites where citizens seek either information or services.

  13. Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base.

    PubMed

    Funakoshi, Minoru; Tomko, Robert J; Kobayashi, Hideki; Hochstrasser, Mark

    2009-05-29

    The central protease of eukaryotes, the 26S proteasome, has a 20S proteolytic core particle (CP) and an attached 19S regulatory particle (RP). The RP is further subdivided into lid and base subcomplexes. Little is known about RP assembly. Here, we show that four conserved assembly factors govern biogenesis of the yeast RP base. Nas2 forms a complex with the Rpt4 and Rpt5 ATPases and enhances 26S proteasome formation in vivo and in vitro. Other RP subcomplexes contain Hsm3, which is related to mammalian proteasome subunit S5b. Hsm3 also contributes to base assembly. Larger Hsm3-containing complexes include two additional proteins, Nas6 and Rpn14, which function as assembly chaperones as well. Specific deletion combinations affecting these four factors cause severe perturbations to RP assembly. Our results demonstrate that proteasomal RP biogenesis requires multiple, functionally overlapping chaperones and suggest a model in which subunits form specific subcomplexes that then assemble into the base.

  14. The physical and psychological factors governing sound-image quality

    NASA Astrophysics Data System (ADS)

    Kurozumi, K.; Ohgushi, K.

    1984-03-01

    One of the most important psychological impressions produced by a conventional two-loudspeakers reproduction-system is a localization of the sound image in the horizontal plane. The sound image is localized to some degree by varying the level and the time differences of the two acoustic signals. Even if the sound image was localized in the same direction, different impressions - for example, a feeling of the width of the sound image - are sometimes produced. These different impressions are explained by the phrase sound-image quality. The purpose is to find out the psychological and physical factors governing sound-image quality. To begin with, the effect on sound-image quality of varying the cross-correlation coefficient for white noise is investigated. A number of studies were performed in which the relationship between the cross-correlation coefficient and the sound-image quality were investigated.

  15. The Future of Government Funding for Persons with Disabilities: Some Key Factors.

    ERIC Educational Resources Information Center

    Ross, E. Clarke

    1980-01-01

    The paper identifies and discusses key factors associated with government funding for disabled individuals. An introductory section traces the growth of public expenditures in recent years. Five key factors affecting government funding are examined (sample subtopics in parentheses): state government tax and spending limits (Proposition 13 and the…

  16. Factors governing the deep ventilation of the Red Sea

    NASA Astrophysics Data System (ADS)

    Papadopoulos, Vassilis P.; Zhan, Peng; Sofianos, Sarantis S.; Raitsos, Dionysios E.; Qurban, Mohammed; Abualnaja, Yasser; Bower, Amy; Kontoyiannis, Harilaos; Pavlidou, Alexandra; Asharaf, T. T. Mohamed; Zarokanellos, Nikolaos; Hoteit, Ibrahim

    2015-11-01

    A variety of data based on hydrographic measurements, satellite observations, reanalysis databases, and meteorological observations are used to explore the interannual variability and factors governing the deep water formation in the northern Red Sea. Historical and recent hydrographic data consistently indicate that the ventilation of the near-bottom layer in the Red Sea is a robust feature of the thermohaline circulation. Dense water capable to reach the bottom layers of the Red Sea can be regularly produced mostly inside the Gulfs of Aqaba and Suez. Occasionally, during colder than usual winters, deep water formation may also take place over coastal areas in the northernmost end of the open Red Sea just outside the Gulfs of Aqaba and Suez. However, the origin as well as the amount of deep waters exhibit considerable interannual variability depending not only on atmospheric forcing but also on the water circulation over the northern Red Sea. Analysis of several recent winters shows that the strength of the cyclonic gyre prevailing in the northernmost part of the basin can effectively influence the sea surface temperature (SST) and intensify or moderate the winter surface cooling. Upwelling associated with periods of persistent gyre circulation lowers the SST over the northernmost part of the Red Sea and can produce colder than normal winter SST even without extreme heat loss by the sea surface. In addition, the occasional persistence of the cyclonic gyre feeds the surface layers of the northern Red Sea with nutrients, considerably increasing the phytoplankton biomass.

  17. Risk Governance of Multiple Natural Hazards: Centralized versus Decentralized Approach in Europe

    NASA Astrophysics Data System (ADS)

    Komendantova, Nadejda; Scolobig, Anna; Vinchon, Charlotte

    2014-05-01

    The multi-risk approach is a relatively new field and its definition includes the need to consider multiple hazards and vulnerabilities in their interdependency (Selva, 2013) and the current multi-hazards disasters, such as the 2011 Tohoku earthquake, tsunami and nuclear catastrophe, showed the need for a multi-risk approach in hazard mitigation and management. Our knowledge about multi-risk assessment, including studies from different scientific disciplines and developed assessment tools, is constantly growing (White et al., 2001). However, the link between scientific knowledge, its implementation and the results in terms of improved governance and decision-making have gained significantly less attention (IRGC, 2005; Kappes et al., 2012), even though the interest to risk governance, in general, has increased significantly during the last years (Verweiy and Thompson, 2006). Therefore, the key research question is how risk assessment is implemented and what is the potential for the implementation of a multi-risk approach in different governance systems across Europe. More precisely, how do the characteristics of risk governance, such as the degree of centralization versus decentralization, influence the implementation of a multi-risk approach. The methodology of this research includes comparative case study analysis of top-down and bottom-up interactions in governance in the city of Naples, (Italy), where the institutional landscape is marked by significant autonomy of Italian regions in decision-making processes for assessing the majority of natural risks, excluding volcanic, and in Guadeloupe, French West Indies, an overseas department of France, where the decision-making process is marked by greater centralization in decision making associated with a well established state governance within regions, delegated to the prefect and decentralised services of central ministries. The research design included documentary analysis and extensive empirical work involving

  18. Risk Governance of Multiple Natural Hazards: Centralized versus Decentralized Approach in Europe

    NASA Astrophysics Data System (ADS)

    Komendantova, Nadejda; Scolobig, Anna; Vinchon, Charlotte

    2014-05-01

    The multi-risk approach is a relatively new field and its definition includes the need to consider multiple hazards and vulnerabilities in their interdependency (Selva, 2013) and the current multi-hazards disasters, such as the 2011 Tohoku earthquake, tsunami and nuclear catastrophe, showed the need for a multi-risk approach in hazard mitigation and management. Our knowledge about multi-risk assessment, including studies from different scientific disciplines and developed assessment tools, is constantly growing (White et al., 2001). However, the link between scientific knowledge, its implementation and the results in terms of improved governance and decision-making have gained significantly less attention (IRGC, 2005; Kappes et al., 2012), even though the interest to risk governance, in general, has increased significantly during the last years (Verweiy and Thompson, 2006). Therefore, the key research question is how risk assessment is implemented and what is the potential for the implementation of a multi-risk approach in different governance systems across Europe. More precisely, how do the characteristics of risk governance, such as the degree of centralization versus decentralization, influence the implementation of a multi-risk approach. The methodology of this research includes comparative case study analysis of top-down and bottom-up interactions in governance in the city of Naples, (Italy), where the institutional landscape is marked by significant autonomy of Italian regions in decision-making processes for assessing the majority of natural risks, excluding volcanic, and in Guadeloupe, French West Indies, an overseas department of France, where the decision-making process is marked by greater centralization in decision making associated with a well established state governance within regions, delegated to the prefect and decentralised services of central ministries. The research design included documentary analysis and extensive empirical work involving

  19. Murine pheromone proteins constitute a context-dependent combinatorial code governing multiple social behaviors.

    PubMed

    Kaur, Angeldeep W; Ackels, Tobias; Kuo, Tsung-Han; Cichy, Annika; Dey, Sandeepa; Hays, Cristen; Kateri, Maria; Logan, Darren W; Marton, Tobias F; Spehr, Marc; Stowers, Lisa

    2014-04-24

    During social interactions, an individual's behavior is largely governed by the subset of signals emitted by others. Discrimination of "self" from "other" regulates the territorial urine countermarking behavior of mice. To identify the cues for this social discrimination and understand how they are interpreted, we designed an olfactory-dependent countermarking assay. We find major urinary proteins (MUPs) sufficient to elicit countermarking, and unlike other vomeronasal ligands that are detected by specifically tuned sensory neurons, MUPs are detected by a combinatorial strategy. A chemosensory signature of "self" that modulates behavior is developed via experience through exposure to a repertoire of MUPs. In contrast, aggression can be elicited by MUPs in an experience-independent but context-dependent manner. These findings reveal that individually emitted chemical cues can be interpreted based on their combinatorial permutation and relative ratios, and they can transmit both fixed and learned information to promote multiple behaviors. PMID:24766811

  20. Murine pheromone proteins constitute a context-dependent combinatorial code governing multiple social behaviors.

    PubMed

    Kaur, Angeldeep W; Ackels, Tobias; Kuo, Tsung-Han; Cichy, Annika; Dey, Sandeepa; Hays, Cristen; Kateri, Maria; Logan, Darren W; Marton, Tobias F; Spehr, Marc; Stowers, Lisa

    2014-04-24

    During social interactions, an individual's behavior is largely governed by the subset of signals emitted by others. Discrimination of "self" from "other" regulates the territorial urine countermarking behavior of mice. To identify the cues for this social discrimination and understand how they are interpreted, we designed an olfactory-dependent countermarking assay. We find major urinary proteins (MUPs) sufficient to elicit countermarking, and unlike other vomeronasal ligands that are detected by specifically tuned sensory neurons, MUPs are detected by a combinatorial strategy. A chemosensory signature of "self" that modulates behavior is developed via experience through exposure to a repertoire of MUPs. In contrast, aggression can be elicited by MUPs in an experience-independent but context-dependent manner. These findings reveal that individually emitted chemical cues can be interpreted based on their combinatorial permutation and relative ratios, and they can transmit both fixed and learned information to promote multiple behaviors.

  1. Multiple factors in the reptile extinctions of the Cretaceous period.

    PubMed

    Cloudsley-Thompson, J

    2001-08-01

    The selective extinction of the dinosaurs and other giant reptiles has long been a topic of speculation and controversy. Everyone is familiar with the theory of the giant bollide colliding with Earth. But, would it not be more likely that that multiple factors acted over a relatively long period of time to produce this mass extinction?

  2. Pesticides in surface waters: distribution, trends, and governing factors

    USGS Publications Warehouse

    Larson, Steven J.; Capel, Paul D.; Majewski, Michael

    1997-01-01

    Pesticde use in agriculture and non-agriculture settings has increased dramatically over the last several decades. Concern about adverse effects on the environment and human health has spurred an enormous amount of research into their environmental behavior and fate. Pesticides in Surface Waters presents a comprehensive summary of this research. This book evaluates published studies that focus on measuring pesticide concentration. The studies chosen include peer reviewed scientific literature, government reports, laboratory studies, and those using microcosms and artificial streams and ponds. The authors used this information to develop their overview of pesticide contamination of surface waters. The exhaustive compilation of data along with the fundamental science make this book essential for those involved in pesticide use, environmental protection, water quality, and human or ecological risk assessment. Pesticides in Surface Waters covers the results of actual studies, sources of pesticides to surface water, fate and transport, and environmental significance. Hundreds of data-packed tables, maps, charts, and drawings illustrate the key points, making research and application easy and cost effective.

  3. Factors Governing Fibrillogenesis of Polypeptide Chains Revealed by Lattice Models

    NASA Astrophysics Data System (ADS)

    Li, Mai Suan; Co, Nguyen Truong; Reddy, Govardhan; Hu, Chin-Kun; Straub, J. E.; Thirumalai, D.

    2010-11-01

    Using lattice models we explore the factors that determine the tendencies of polypeptide chains to aggregate by exhaustively sampling the sequence and conformational space. The morphologies of the fibril-like structures and the time scales (τfib) for their formation depend on a balance between hydrophobic and Coulomb interactions. The extent of population of an ensemble of N* structures, which are fibril-prone structures in the spectrum of conformations of an isolated protein, is the major determinant of τfib. This observation is used to determine the aggregating sequences by exhaustively exploring the sequence space, thus providing a basis for genome wide search of fragments that are aggregation prone.

  4. Factors Governing the Accuracy of Subvisible Particle Counting Methods.

    PubMed

    Ríos Quiroz, Anacelia; Finkler, Christof; Huwyler, Joerg; Mahler, Hanns-Christian; Schmidt, Roland; Koulov, Atanas V

    2016-07-01

    A number of new techniques for subvisible particle characterization in biotechnological products have emerged in the last decade. Although the pharmaceutical community is actively using them, the current knowledge about the analytical performance of some of these tools is still inadequate to support their routine use in the development of biopharmaceuticals (especially in the case of submicron methods). With the aim of increasing this knowledge and our understanding of the most prominent techniques for subvisible particle characterization, this study reports the results of a systematic evaluation of their accuracy. Our results showed a marked overcounting effect especially for low concentrated samples and particles fragile in nature. Furthermore, we established the relative sample size distribution as the most important contributor to an instrument's performance in accuracy counting. The smaller the representation of a particle size within a solution, the more difficulty the instruments had in providing an accurate count. These findings correlate with a recent study examining the principal factors influencing the precision of the subvisible particle measurements. A more thorough understanding of the capabilities of the different particle characterization methods provided here will help guide the application of these methods and the interpretation of results in subvisible particle characterization studies.

  5. Factors Governing the Accuracy of Subvisible Particle Counting Methods.

    PubMed

    Ríos Quiroz, Anacelia; Finkler, Christof; Huwyler, Joerg; Mahler, Hanns-Christian; Schmidt, Roland; Koulov, Atanas V

    2016-07-01

    A number of new techniques for subvisible particle characterization in biotechnological products have emerged in the last decade. Although the pharmaceutical community is actively using them, the current knowledge about the analytical performance of some of these tools is still inadequate to support their routine use in the development of biopharmaceuticals (especially in the case of submicron methods). With the aim of increasing this knowledge and our understanding of the most prominent techniques for subvisible particle characterization, this study reports the results of a systematic evaluation of their accuracy. Our results showed a marked overcounting effect especially for low concentrated samples and particles fragile in nature. Furthermore, we established the relative sample size distribution as the most important contributor to an instrument's performance in accuracy counting. The smaller the representation of a particle size within a solution, the more difficulty the instruments had in providing an accurate count. These findings correlate with a recent study examining the principal factors influencing the precision of the subvisible particle measurements. A more thorough understanding of the capabilities of the different particle characterization methods provided here will help guide the application of these methods and the interpretation of results in subvisible particle characterization studies. PMID:27287519

  6. Factors governing sustainable groundwater pumping near a river

    SciTech Connect

    Zhang, Y.; Hubbard, S.S.; Finsterle, S.

    2011-01-15

    The objective of this paper is to provide new insights into processes affecting riverbank filtration (RBF). We consider a system with an inflatable dam installed for enhancing water production from downstream collector wells. Using a numerical model, we investigate the impact of groundwater pumping and dam operation on the hydrodynamics in the aquifer and water production. We focus our study on two processes that potentially limit water production of an RBF system: the development of an unsaturated zone and riverbed clogging. We quantify river clogging by calibrating a time-dependent riverbed permeability function based on knowledge of pumping rate, river stage, and temperature. The dynamics of the estimated riverbed permeability reflects clogging and scouring mechanisms. Our results indicate that (1) riverbed permeability is the dominant factor affecting infiltration needed for sustainable RBF production; (2) dam operation can influence pumping efficiency and prevent the development of an unsaturated zone beneath the riverbed only under conditions of sufficient riverbed permeability; (3) slow river velocity, caused by dam raising during summer months, may lead to sedimentation and deposition of fine-grained material within the riverbed, which may clog the riverbed, limiting recharge to the collector wells and contributing to the development of an unsaturated zone beneath the riverbed; and (4) higher river flow velocities, caused by dam lowering during winter storms, scour the riverbed an thus increase its permeability. These insights can be used as the basis for developing sustainable water management of a RBF system.

  7. Factors governing sustainable groundwater pumping near a river.

    PubMed

    Zhang, Yingqi; Hubbard, Susan; Finsterle, Stefan

    2011-01-01

    The objective of this paper was to provide new insights into processes affecting riverbank filtration (RBF). We consider a system with an inflatable dam installed for enhancing water production from downstream collector wells. Using a numerical model, we investigate the impact of groundwater pumping and dam operation on the hydrodynamics in the aquifer and water production. We focus our study on two processes that potentially limit water production of an RBF system: the development of an unsaturated zone and riverbed clogging. We quantify river clogging by calibrating a time-dependent riverbed permeability function based on knowledge of pumping rate, river stage, and temperature. The dynamics of the estimated riverbed permeability reflects clogging and scouring mechanisms. Our results indicate that (1) riverbed permeability is the dominant factor affecting infiltration needed for sustainable RBF production; (2) dam operation can influence pumping efficiency and prevent the development of an unsaturated zone beneath the riverbed only under conditions of sufficient riverbed permeability; (3) slow river velocity, caused by dam raising during summer months, may lead to sedimentation and deposition of fine-grained material within the riverbed, which may clog the riverbed, limiting recharge to the collector wells and contributing to the development of an unsaturated zone beneath the riverbed; and (4) higher river flow velocities, caused by dam lowering during winter storms, scour the riverbed and thus increase its permeability. These insights can be used as the basis for developing sustainable water management of a RBF system. PMID:20807247

  8. [Risk factors of osteoporosis in women with multiple sclerosis].

    PubMed

    Khachanova, N V; Demina, T L; Smirnov, A V; Gusev, E I

    2006-01-01

    Multiple sclerosis (MS) is a progressive disease that leads to early disability of young adults at a reproductive age. Motor disturbances caused by progressive pyramidal deficit and cerebellar dysfunction, accompanied by ataxia with frequent falls, and early decrease of physical activity are risk factors of osteoporosis in MS patients. A relapsing-remitting course of the disease with frequent attacks demands multiple courses of steroid therapy. Long-term steroid treatment causes bone loss and development of secondary osteoporosis. We have shown that reduced bone mineral density (BMD) in lumbar spine and femoral neck is associated with high level of EDSS score caused by the combination of moderate pyramidal and cerebellar dysfunction. An additional risk factor of osteoporosis in MS patients is low body weight. The glucocorticoid therapy does not exert a negative impact on BMD in lumbar spine and femoral neck in patients with MS.

  9. Hypoxia inducible factor-1 alpha and multiple myeloma

    PubMed Central

    Tiwary, Bhupendra Nath

    2016-01-01

    Rapid tumor growth creates a state of hypoxia in the tumor microenvironment and results in release of hypoxia inducible factor-1 alpha (HiF-1α) in the local milieu. Hypoxia inducible factor activity is deregulated in many human cancers, especially those that are highly hypoxic. In multiple myeloma (MM) in initial stages of disease establishment, the hypoxic bone marrow microenvironment supports the initial survival and growth of the myeloma cells. Hypoxic tumour cells are usually resistant to radiotherapy and most conventional chemotherapeutic agents, rendering them highly aggressive and metastatic. Therefore, HIF is an attractive, although challenging, therapeutic target in MM directly or indirectly in recent years. PMID:26900575

  10. Factors associated with reporting multiple causes of death

    PubMed Central

    Wall, Melanie M; Huang, Jinzhou; Oswald, John; McCullen, Diane

    2005-01-01

    Background There is analytical potential for multiple cause of death data collected from death certificates. This study examines relationships of multiple causes of death as a function of factors available on the death certificate (demographics of decedent, place of death, type of certifier, disposal method, whether an autopsy was performed, and year of death). Methods Data from 326,332 Minnesota death certificates from 1990–1998 are examined. Underlying and non-underlying causes of death are examined (based on record axis codes) as well as demographic and death-related covariates. Associations between covariates and prevalence of multiple causes of death and conditional probability of underlying compared to non-underlying causes of death are examined. The occurrence of ischemic heart disease or diabetes as underlying causes are specifically examined. Results Both the probability of multiple causes of death and the proportion of underlying cause compared to non-underlying cause of death are associated with demographic characteristics of the deceased and other non-medical conditions related to filing death certificate such as place of death. Conclusions Multiple cause of death data provide a potentially useful way of looking for inaccuracies in reporting of causes of death. Differences across demographics in the proportion of time a cause is selected as underlying compared to non-underlying exist and can potentially provide useful information about the overall impact of causes of death in different populations. PMID:15655070

  11. Pesticides in ground water: distribution, trends, and governing factors

    USGS Publications Warehouse

    Barbash, Jack; Resek, Elizabeth A.

    1997-01-01

    A comprehensive review of published information on the distribution and behavior of pesticides and their transformation products in ground water indicates that pesticides from every chemical class have been detected in ground waters of the United States. Many of these compounds are commonly present at low concentrations in ground water beneath agricultural land. Little information is available on their occurrence beneath non-agricultural land, although the intensity of their use in such areas (on lawns, golf courses, rights of way, timberlands, etc.) is often comparable to, or greater than agricultural use. Information on pesticides in ground water is not sufficient to provide either a statistically representative view of pesticide occurrence in ground water across the United States, or an indication of long-term trends or changes in the severity or extent of this contamination over the past three decades. This is largely due to wide variations in analytical detection limits, well selection procedures, and other design features among studies conducted in different areas or at different times. Past approaches have not been well suited for distinguishing "point source" from "nonpoint source" pesticide contamination. Among the variety of natural and anthropogenic factors examined, those that appear to be most strongly associated with the intensity of pesticide contamination of ground water are the depth, construction and age of the sampled wells, the amount of recharge (by precipitation or irrigation), and the depth of tillage. Approaches commonly employed for predicting pesticide distributions in the subsurface--including computer simulations, indicator solutes (e.g., nitrate or tritium), and ground-water vulnerability assessments--generally provide unreliable predictions of pesticide occurrence in ground water. Such difficulties may arise largely from a general failure to account for the preferential transport of pesticides in the subsurface. Significant

  12. Factors governing risk of cougar attacks on humans

    USGS Publications Warehouse

    Mattson, David; Logan, Kenneth; Sweanor, Linda

    2011-01-01

    Since the 1980s wildlife managers in the United States and Canada have expressed increasing concern about the physical threat posed by cougars (Puma concolor) to humans. We developed a conceptual framework and analyzed 386 human–cougar encounters (29 fatal attacks, 171 instances of nonfatal contact, and 186 close-threatening encounters) to provide information relevant to public safety. We conceived of human injury and death as the outcome of 4 transitions affected by different suites of factors: (1) a human encountering a cougar: (2) given an encounter, odds that the cougar would be aggressive; (3) given aggression, odds that the cougar would attack; and (4) given an attack, odds that the human would die. We developed multivariable logistic regression models to explain variation in odds at transitions three and four using variables pertaining to characteristics of involved people and cougars. Young (≤ 2.5 years) or unhealthy (by weight, condition, or disease) cougars were more likely than any others to be involved in close (typically <5 m) encounters that threatened the involved person. Of cougars in close encounters, females were more likely than males to attack, and of attacking animals, adults were more likely than juveniles to kill the victim (32% versus 9% fatality, respectively). During close encounters, victims who used a weapon killed the involved cougar in 82% of cases. Other mitigating behaviors (e.g., yelling, backing away, throwing objects, increasing stature) also substantially lessened odds of attack. People who were moving quickly or erratically when an encounter happened (running, playing, skiing, snowshoeing, biking, ATV-riding) were more likely to be attacked and killed compared to people who were less active (25% versus 8% fatality). Children (≤ 10 years) were more likely than single adults to be attacked, but intervention by people of any age reduced odds of a child’s death by 4.6×. Overall, cougar attacks on people in Canada and the

  13. Space adaptation syndrome: multiple etiological factors and individual differences

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; DiZio, P.

    1991-01-01

    Space motion sickness is a significant operational concern in the American and Soviet space programs. Nearly 70% of all astronauts and cosmonauts are affected to some degree during their first several days of flight. It is now beginning to appear that space motion sickness like terrestrial motion sickness is the consequence of multiple etiological factors. As we come to understand basic mechanisms of spatial orientation and sensory-motor adaptation we can begin to predict etiological factors in different motion environments. Individuals vary greatly in the extent to which they are susceptible to these different factors. However, individuals seem to be relatively self-consistent in terms of their rates of adaptation to provocative stimulation and their retention of adaptation. Attempts to relate susceptibility to motion sickness during the microgravity phases of parabolic flight maneuvers to vestibular function under 1G and 0G test conditions are described.

  14. Nutritional factors and multiple sclerosis in Gorski Kotar, Croatia.

    PubMed

    Sepcić, J; Mesaros, E; Materljan, E; Sepić-Grahovac, D

    1993-01-01

    An analysis was made of the possible influence of nutritional factors on the etiology of multiple sclerosis in Gorski Kotar (Croatia), a high-risk zone for this disease. A total of 46 MS patients and 92 controls, native-born residents of the area studied, participated in a case-control study. The questionnaire comprised 51 questions concerning dietary habits. An odds ratio (OR) estimate was obtained for all the factors which were more frequently found in the patients than in the controls. Large differences were found in the daily consumption of different quantities of full fat unskimmed milk (OR 21.7; chi 2 42.34; LL 7.12), potatoes with lard and fresh or smoked meat (OR 20.7; chi 2 15.52; LL 2.72), and new potatoes (OR 20.7; chi 2 15.52; LL 2.72). The consumption of unpasteurized milk, animal fat, smoked meat and potatoes are nutritional risk factors which could have an influence on the severity of primary demyelinization in a high-risk area for multiple sclerosis.

  15. Modifiable factors influencing relapses and disability in multiple sclerosis.

    PubMed

    D'hooghe, M B; Nagels, G; Bissay, V; De Keyser, J

    2010-07-01

    A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetanus appear to be safe. Surgery, general and epidural anaesthesia, and physical trauma are not associated with an increased risk of relapses. Factors that have been associated with a reduced relapse rate are pregnancy, exclusive breastfeeding, sunlight exposure and higher vitamin D levels. A number of medications, including hormonal fertility treatment, seem to be able to trigger relapses. Factors that may worsen progression of disability include stressful life events, radiotherapy to the head, low levels of physical activity and low vitamin D levels. Strong evidence suggests that smoking promotes disease progression, both clinically and on brain magnetic resonance imaging. There is no evidence for an increased progression of disability following childbirth in women with multiple sclerosis. Moderate alcohol intake and exercise might have a neuroprotective effect, but this needs to be confirmed. PMID:20483884

  16. Fissile mass-multiplication factor correlation for Pu measurement

    SciTech Connect

    Lu, Ming-Shih; Teichmann, T.; De Ridder, P.; Verrecchia, G.P.D.; Chare, P.; Vocino, V.

    1993-06-01

    An empirical correlation between the fissile mass and the leakage multiplication factor, as determined by High Level Neutron Coincidence (HLNC) counting, was developed based on available measurement data. This correlation has been used successfully for the simulation of HLNC counting. With the singles count rate (totals), the correlation can be used to obtain a quick estimate of the plutonium mass of the sample in less time than required to measure the real coincidence count rate. The correlation can also be used to evaluate samples contaminated with ({alpha},n) sources such as fluorine.

  17. Multiple response optimization for higher dimensions in factors and responses

    DOE PAGESBeta

    Lu, Lu; Chapman, Jessica L.; Anderson-Cook, Christine M.

    2016-07-19

    When optimizing a product or process with multiple responses, a two-stage Pareto front approach is a useful strategy to evaluate and balance trade-offs between different estimated responses to seek optimum input locations for achieving the best outcomes. After objectively eliminating non-contenders in the first stage by looking for a Pareto front of superior solutions, graphical tools can be used to identify a final solution in the second subjective stage to compare options and match with user priorities. Until now, there have been limitations on the number of response variables and input factors that could effectively be visualized with existing graphicalmore » summaries. We present novel graphical tools that can be more easily scaled to higher dimensions, in both the input and response spaces, to facilitate informed decision making when simultaneously optimizing multiple responses. A key aspect of these graphics is that the potential solutions can be flexibly sorted to investigate specific queries, and that multiple aspects of the solutions can be simultaneously considered. As a result, recommendations are made about how to evaluate the impact of the uncertainty associated with the estimated response surfaces on decision making with higher dimensions.« less

  18. IRINI: random group allocation of multiple prognostic factors.

    PubMed

    Kasturi, Jyotsna; Geisler, John G; Liu, Jianying; Kirchner, Thomas; Amaratunga, Dhammika; Lubomirski, Mariusz

    2011-05-01

    Statistically sound experimental design in pharmacology studies ensures that the known prognostic factors, if any, are equally represented across investigational groups to avoid bias and imbalance which could render the experiment invalid or lead to false conclusions. Complete randomization can be effective to reduce bias in the created groups especially in large sample size situations. However, in small studies which involve only few treatment subjects, as in preclinical trials, there is a high chance of imbalance. The effects of this imbalance may be removed through covariate analysis or prevented with stratified randomization, however small studies limit the number of covariates to be analyzed this way. The problem is accentuated when there are multiple baseline covariates with varying scales and magnitudes to be considered in the randomization, and creating a balanced solution becomes a combinatorial challenge. Our method, IRINI, uses an optimization technique to achieve treatment to subject group allocation across multiple prognostic factors concurrently. It ensures that the created groups are equal in size and statistically comparable in terms of mean and variance. This method is a novel application of genetic algorithms to solve the allocation problem and simultaneously ensure quality, speed of the results and randomness of the process. Results from preclinical trials demonstrate the effectiveness of the method.

  19. The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis

    PubMed Central

    Carrasco, Daniel R.; Sukhdeo, Kumar; Protopopova, Marina; Sinha, Raktim; Enos, Miriam; Carrasco, Daniel E.; Zheng, Mei; Mani, Mala; Henderson, Joel; Pinkus, Geraldine S.; Munshi, Nikhil; Horner, James; Ivanova, Elena V.; Protopopov, Alexei; Anderson, Kenneth C.; Tonon, Giovanni; DePinho, Ronald A.

    2007-01-01

    Summary Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis. PMID:17418411

  20. Factors Influencing the Design, Establishment, Administration, and Governance of Correctional Education for Females

    ERIC Educational Resources Information Center

    Ellis, Johnica; McFadden, Cheryl; Colaric, Susan

    2008-01-01

    This article summarizes the results of a study conducted to investigate factors influencing the organizational design, establishment, administration, and governance of correctional education for females. The research involved interviews with correctional and community college administrators and practitioners representing North Carolina female…

  1. Factors in the Transfer of Governance-Facilitation Skills within Farmers' Marketing Organizations in Uganda

    ERIC Educational Resources Information Center

    Miiro, Richard F.; Mazur, Robert E.; Matsiko, Frank B.

    2012-01-01

    Purpose: Training transfer has been examined for formal industrial and service organizations in developed countries but rarely for rural organizations in sub-Saharan Africa. This study sought to identify transfer system factors that best explain the transfer of governance-facilitation skills provided to leaders of farmers' marketing organizations…

  2. pH-Dependent Interactions in Dimers Govern the Mechanics and Structure of von Willebrand Factor.

    PubMed

    Müller, Jochen P; Löf, Achim; Mielke, Salomé; Obser, Tobias; Bruetzel, Linda K; Vanderlinden, Willem; Lipfert, Jan; Schneppenheim, Reinhard; Benoit, Martin

    2016-07-26

    Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that is activated for hemostasis by increased hydrodynamic forces at sites of vascular injury. Here, we present data from atomic force microscopy-based single-molecule force measurements, atomic force microscopy imaging, and small-angle x-ray scattering to show that the structure and mechanics of VWF are governed by multiple pH-dependent interactions with opposite trends within dimeric subunits. In particular, the recently discovered strong intermonomer interaction, which induces a firmly closed conformation of dimers and crucially involves the D4 domain, was observed with highest frequency at pH 7.4, but was essentially absent at pH values below 6.8. However, below pH 6.8, the ratio of compact dimers increased with decreasing pH, in line with a previous transmission electron microscopy study. These findings indicated that the compactness of dimers at pH values below 6.8 is promoted by other interactions that possess low mechanical resistance compared with the strong intermonomer interaction. By investigating deletion constructs, we found that compactness under acidic conditions is primarily mediated by the D4 domain, i.e., remarkably by the same domain that also mediates the strong intermonomer interaction. As our data suggest that VWF has the highest mechanical resistance at physiological pH, local deviations from physiological pH (e.g., at sites of vascular injury) may represent a means to enhance VWF's hemostatic activity where needed. PMID:27463134

  3. pH-Dependent Interactions in Dimers Govern the Mechanics and Structure of von Willebrand Factor.

    PubMed

    Müller, Jochen P; Löf, Achim; Mielke, Salomé; Obser, Tobias; Bruetzel, Linda K; Vanderlinden, Willem; Lipfert, Jan; Schneppenheim, Reinhard; Benoit, Martin

    2016-07-26

    Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that is activated for hemostasis by increased hydrodynamic forces at sites of vascular injury. Here, we present data from atomic force microscopy-based single-molecule force measurements, atomic force microscopy imaging, and small-angle x-ray scattering to show that the structure and mechanics of VWF are governed by multiple pH-dependent interactions with opposite trends within dimeric subunits. In particular, the recently discovered strong intermonomer interaction, which induces a firmly closed conformation of dimers and crucially involves the D4 domain, was observed with highest frequency at pH 7.4, but was essentially absent at pH values below 6.8. However, below pH 6.8, the ratio of compact dimers increased with decreasing pH, in line with a previous transmission electron microscopy study. These findings indicated that the compactness of dimers at pH values below 6.8 is promoted by other interactions that possess low mechanical resistance compared with the strong intermonomer interaction. By investigating deletion constructs, we found that compactness under acidic conditions is primarily mediated by the D4 domain, i.e., remarkably by the same domain that also mediates the strong intermonomer interaction. As our data suggest that VWF has the highest mechanical resistance at physiological pH, local deviations from physiological pH (e.g., at sites of vascular injury) may represent a means to enhance VWF's hemostatic activity where needed.

  4. The Role of Multiple Transcription Factors In Archaeal Gene Expression

    SciTech Connect

    Charles J. Daniels

    2008-09-23

    Since the inception of this research program, the project has focused on two central questions: What is the relationship between the 'eukaryal-like' transcription machinery of archaeal cells and its counterparts in eukaryal cells? And, how does the archaeal cell control gene expression using its mosaic of eukaryal core transcription machinery and its bacterial-like transcription regulatory proteins? During the grant period we have addressed these questions using a variety of in vivo approaches and have sought to specifically define the roles of the multiple TATA binding protein (TBP) and TFIIB-like (TFB) proteins in controlling gene expression in Haloferax volcanii. H. volcanii was initially chosen as a model for the Archaea based on the availability of suitable genetic tools; however, later studies showed that all haloarchaea possessed multiple tbp and tfb genes, which led to the proposal that multiple TBP and TFB proteins may function in a manner similar to alternative sigma factors in bacterial cells. In vivo transcription and promoter analysis established a clear relationship between the promoter requirements of haloarchaeal genes and those of the eukaryal RNA polymerase II promoter. Studies on heat shock gene promoters, and the demonstration that specific tfb genes were induced by heat shock, provided the first indication that TFB proteins may direct expression of specific gene families. The construction of strains lacking tbp or tfb genes, coupled with the finding that many of these genes are differentially expressed under varying growth conditions, provided further support for this model. Genetic tools were also developed that led to the construction of insertion and deletion mutants, and a novel gene expression scheme was designed that allowed the controlled expression of these genes in vivo. More recent studies have used a whole genome array to examine the expression of these genes and we have established a linkage between the expression of specific tfb

  5. CD200 is a new prognostic factor in multiple myeloma.

    PubMed

    Moreaux, Jerome; Hose, Dirk; Reme, Thierry; Jourdan, Eric; Hundemer, Michael; Legouffe, Eric; Moine, Philippe; Bourin, Philippe; Moos, Marion; Corre, Jill; Möhler, Thomas; De Vos, John; Rossi, Jean Francois; Goldschmidt, Hartmut; Klein, Bernard

    2006-12-15

    Using Affymetrix microarrays, we identified the expression of the CD200 gene in multiple myeloma cells (MMCs) of 112 patients with newly diagnosed multiple myeloma (MM). The CD200 gene was either absent or present (Affymetrix call) in 22% and 78% of MMCs, respectively. The CD200 gene is not expressed in cells of the patients' bone marrow (BM). CD200 is a membrane glycoprotein that imparts an immunoregulatory signal through CD200R, leading to the suppression of T-cell-mediated immune responses. Patients with CD200(absent) MMCs have an increased event-free survival (EFS; 24 months) compared with patients with CD200(present) MMCs (14 months), after high-dose therapy and stem cell transplantation. In a Cox proportional-hazard model, the absence or presence of CD200 expression in MMCs is predictive for EFS for patients independently of ISS stage or beta2M serum levels. Thus, CD200 is an independent prognosis factor for patients with MM that could represent a new therapeutic target in MM.

  6. Confirmatory factor analysis of the Penn State Worry Questionnaire: Multiple factors or method effects?

    PubMed

    Brown, Timothy A

    2003-12-01

    The latent structure of the Penn State Worry Questionnaire (PSWQ) was evaluated with confirmatory factor analyses (CFAs) in 1200 outpatients with DSM-IV anxiety and mood disorders. Of particular interest was the comparative fit and interpretability of a two-factor solution (cf. Behaviour Research and Therapy 40 (2002) 313) vs. a one-factor model that specified method effects arising from five reverse-worded items. Consistent with prediction, the superiority of the one-factor model was demonstrated in split-sample CFA replications (ns=600). Multiple-group CFAs indicated that the measurement properties of the PSWQ were invariant in male and female patients. In addition to their direct relevance to the psychometrics of the PSWQ, the results are discussed in regard to methodological considerations for using factor analytic methods in the evaluation of psychological tests.

  7. The multiple meanings of global health governance: a call for conceptual clarity

    PubMed Central

    2014-01-01

    Background The term global health governance (GHG) is now widely used, with over one thousand works published in the scholarly literature, almost all since 2002. Amid this rapid growth there is considerable variation in how the term is defined and applied, generating confusion as to the boundaries of the subject, the perceived problems in practice, and the goals to be achieved through institutional reform. Methodology This paper is based on the results of a separate scoping study of peer reviewed GHG research from 1990 onwards which undertook keyword searches of public health and social science databases. Additional works, notably books, book chapters and scholarly articles, not currently indexed, were identified through Web of Science citation searches. After removing duplicates, book reviews, commentaries and editorials, we reviewed the remaining 250 scholarly works in terms of how the concept of GHG is applied. More specifically, we identify what is claimed as constituting GHG, how it is problematised, the institutional features of GHG, and what forms and functions are deemed ideal. Results After examining the broader notion of global governance and increasingly ubiquitous term “global health”, the paper identifies three ontological variations in GHG scholarship - the scope of institutional arrangements, strengths and weaknesses of existing institutions, and the ideal form and function of GHG. This has produced three common, yet distinct, meanings of GHG that have emerged – globalisation and health governance, global governance and health, and governance for global health. Conclusions There is a need to clarify ontological and definitional distinctions in GHG scholarship and practice, and be critically reflexive of their normative underpinnings. This will enable greater precision in describing existing institutional arrangements, as well as serve as a prerequisite for a fuller debate about the desired nature of GHG. PMID:24775919

  8. Multiplicity of mechanisms govern efficacy of anaerobic soil disinfestation for soil-borne disease control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies demonstrated that carbon input type influenced control of various fungi, oomycetes and plant parasitic nematodes with anaerobic soil disinfestation (ASD). Findings implicated multiple mechanisms may contribute to the overall level of disease control attained. In strawberry field trials, ASD ...

  9. Factors governing phytoplankton biomass and production in tropical estuaries of western Taiwan

    NASA Astrophysics Data System (ADS)

    Pan, Ching-Wen; Chuang, Yi-Li; Chou, Lien-Siang; Chen, Meng-Hsien; Lin, Hsing-Juh

    2016-04-01

    Factors governing phytoplankton community composition and production in tropical estuaries remain mostly unknown. We aimed to quantify phytoplankton biomass, production, and community composition seasonally in 2 tropical estuaries with different levels of nutrient concentrations and turbidity, and we compared them with an offshore control site on the western coast of central Taiwan for two years. Phytoplankton biomass and production varied with season and site. Annual integrated primary production showed that these three sites were mesotrophic systems. Spearman rank correlations showed that phytoplankton biomass and production were positively correlated with water temperature, but negatively correlated with turbidity. The threshold of turbidity was 12 Nephelometric Turbidity Units (NTU), above which phytoplankton chlorophyll a concentrations were <0.5 mg m-3, and gross production rate was <100 mg C m-3 d-1. The results of nonmetric multidimensional scaling (MDS) showed that the community was primarily structured by season and secondarily by site. The functional traits further showed that turbidity, water temperature, and SiO2 concentration were governing factors for the variations in the community. In summary, turbidity was the main factor governing phytoplankton biomass and production, whereas water temperature and SiO2 concentration had both a direct effect on production and an indirect effect by changing community composition.

  10. Multiple Sclerosis Associated Risk Factors: A Case-Control Study

    PubMed Central

    POOROLAJAL, Jalal; MAZDEH, Mehrdokht; SAATCHI, Mohammad; TALEBI GHANE, Elaheh; BIDERAFSH, Azam; LOTFI, Bahar; FERYADRES, Mohammad; PAJOHI, Khabat

    2015-01-01

    Background: Hamadan Province is one of the high-risk regions in Iran for Multiple sclerosis (MS). A majority of the epidemiological studies conducted in Iran addressing MS are descriptive. This study was conducted to assess MS and its associated risk factors in Hamadan Province, the west of Iran. Methods: This case-control study compared 100 patients with MS (case group) and 100 patients with acute infectious diseases (control group) from September 2013 to March 2014. A checklist was used to assess the demographic, medical, and family history of the patients. The Friedman-Rosenman questionnaire was also used to assess personality type. Statistical analysis was performed using logistic regression model with Stata 11 software program. Results: The adjusted odds ratio (OR) estimate of MS was 4.37 (95% CI: 2.33, 8.20) for females compared to males; 0.15 (95% CI: 0.06, 0.43) for people aged above 50 years compared to aged 14 to 29 years; 0.44 (95% CI: 0.21, 0.91) for overweight or obese people compared to normal weights. Crude OR indicated a significant association between the occurrence of MS and exclusive breast feeding, season of birth, and smoking. However, the association was not statistically significant after adjustment for other covariates. Conclusion: The risk of MS is significantly lower in male gender, obese/overweight, and old people. Furthermore, non-smoking, non-exclusive breast-feeding, and born in autumn may increase the risk of MS but need further investigation. However, long-term large prospective cohort studies are needed to investigate the true effect of the potential risk factors on MS. PMID:26744707

  11. Do climate factors govern soil microbial community composition and biomass at a regional scale?

    NASA Astrophysics Data System (ADS)

    Ma, L.; Guo, C.; Lü, X.; Yuan, S.; Wang, R.

    2014-12-01

    Soil microbial communities play important role in organic matter decomposition, nutrient cycling and vegetation dynamic. However, little is known about factors driving soil microbial community composition at large scales. The objective of this study was to determine whether climate dominates among environmental factors governing microbial community composition and biomass at a regional scale. Here, we compared soil microbial communities using phospholipid fatty acid method across 7 land use types from 23 locations in North-East China Transect (850 km x 50 km). The results showed that soil water availability and land use changes exhibited the dominant effects on soil microbial community composition and biomass at the regional scale, while climate factors (expressed as a function of large-scale spatial variation) did not show strong relationships with distribution of microbial community composition. Likewise, factors such as spatial structure, soil texture, nutrient availability and vegetation types were not important. Wetter soils had higher contributions of gram-positive bacteria, whereas drier soils had higher contributions of gram-negative bacteria and fungi. Heavily disturbed soils had lower contributions of gram-negative bacteria and fungi than historically disturbed and undisturbed soils. The lowest microbial biomass appeared in the wettest and driest soils. In conclusion, dominant climate factors, commonly known to structure distribution of macroorganisms, were not the most important drivers governing regional pattern of microbial communities because of inclusion of irrigated and managed practices. In comparison, soil water regime and land use types appear to be primary determinants of microbial community composition and biomass.

  12. Analysis of the financial factors governing the profitability of lunar helium-3

    NASA Technical Reports Server (NTRS)

    Kulcinski, G. L.; Thompson, H.; Ott, S.

    1989-01-01

    Financial factors influencing the profitability of the mining and utilization of lunar helium-3 are examined. The analysis addressed the following questions: (1) which financial factors have the greatest leverage on the profitability of He-3; (2) over what range can these factors be varied to keep the He-3 option profitable; and (3) what ultimate effect could this energy source have on the price of electricity for U.S. consumers. Two complementary methods of analysis were used in the assessment: rate of return on incremental investment required and reduction revenue requirements (total cost to customers) achieved. Some of the factors addressed include energy demand, power generation costs with and without fusion, profitability for D-He(3) fusion, annual capital and operating costs, launch mass and costs, He-3 price, and government funding. Specific conclusions are made with respect to each of the companies considered: utilities, lunar mining company, and integrated energy company.

  13. Assessing social capacity and vulnerability of private households to natural hazards - integrating psychological and governance factors

    NASA Astrophysics Data System (ADS)

    Werg, J.; Grothmann, T.; Schmidt, P.

    2013-06-01

    People are unequally affected by extreme weather events in terms of mortality, morbidity and financial losses; this is the case not only for developing, but also for industrialized countries. Previous research has established indicators for identifying who is particularly vulnerable and why, focusing on socio-demographic factors such as income, age, gender, health and minority status. However, these factors can only partly explain the large disparities in the extent to which people are affected by natural hazards. Moreover, these factors are usually not alterable in the short to medium term, which limits their usefulness for strategies of reducing social vulnerability and building social capacity. Based on a literature review and an expert survey, we propose an approach for refining assessments of social vulnerability and building social capacity by integrating psychological and governance factors.

  14. Beyond job security and money: driving factors of motivation for government doctors in India

    PubMed Central

    2014-01-01

    Background Despite many efforts from government to address the shortage of medical officers (MOs) in rural areas, rural health centres continue to suffer from severe shortage of MOs. Lack of motivation to join and continue service in rural areas is a major reason for such shortage. In the present study, we aimed to assess and rank the driving factors of motivation important for in-service MOs in their current job. Methods The study participants included ninety two in-service government MOs from three states in India. The study participants were required to rank 14 factors of motivation important for them in their current job. The factors for the study were selected using Herzberg’s two-factor theory of motivation and the data were collected using an instrument that has an established reliability and validity. Test of Kendall’s coefficient of concordance (W) was carried out to assess the agreement in ranks assigned by participants to various motivation factors. Next, we studied the distributions of ranks of different motivating factors using standard descriptive statistics and box plots, which gave us interesting insights into the strength of agreement of the MOs in assigning ranks to various factors. And finally to assess whether MOs are more intrinsically motivated or extrinsically motivated, we used Kolmogorov-Smirnov test. Results The (W) test indicated statistically significant (P < 0.01) agreement of the participants in assigning ranks. The Kolmogorov-Smirnov test indicated that from policy perspectives, MOs place significantly more motivational importance to intrinsic factors than to extrinsic factors. The study results indicate that job security was the most important factor related to motivation, closely followed by interesting work and respect and recognition. Among the top five preferred factors, three were intrinsic factors indicating a great importance given by MOs to factors beyond money and job security. Conclusion To address the issue of

  15. [Factors of multiple resistance to antibiotics in nodule bacteria].

    PubMed

    Pariĭskaia, A N; Gorelova, O P

    1976-01-01

    Multiple resistance to antibiotics (penicillin, levomycetin, neomycin, tetracycline) was found in 15% of collection strains of nodule bacteria and in strains isolated from natural environment. PMID:1050635

  16. Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

    ERIC Educational Resources Information Center

    Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

    2010-01-01

    The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

  17. Loop-loop interactions govern multiple steps in indole-3-glycerol phosphate synthase catalysis.

    PubMed

    Zaccardi, Margot J; O'Rourke, Kathleen F; Yezdimer, Eric M; Loggia, Laura J; Woldt, Svenja; Boehr, David D

    2014-03-01

    Substrate binding, product release, and likely chemical catalysis in the tryptophan biosynthetic enzyme indole-3-glycerol phosphate synthase (IGPS) are dependent on the structural dynamics of the β1α1 active-site loop. Statistical coupling analysis and molecular dynamic simulations had previously indicated that covarying residues in the β1α1 and β2α2 loops, corresponding to Arg54 and Asn90, respectively, in the Sulfolobus sulfataricus enzyme (ssIGPS), are likely important for coordinating functional motions of these loops. To test this hypothesis, we characterized site mutants at these positions for changes in catalytic function, protein stability and structural dynamics for the thermophilic ssIGPS enzyme. Although there were only modest changes in the overall steady-state kinetic parameters, solvent viscosity and solvent deuterium kinetic isotope effects indicated that these amino acid substitutions change the identity of the rate-determining step across multiple temperatures. Surprisingly, the N90A substitution had a dramatic effect on the general acid/base catalysis of the dehydration step, as indicated by the loss of the descending limb in the pH rate profile, which we had previously assigned to Lys53 on the β1α1 loop. These changes in enzyme function are accompanied with a quenching of ps-ns and µs-ms timescale motions in the β1α1 loop as measured by nuclear magnetic resonance studies. Altogether, our studies provide structural, dynamic and functional rationales for the coevolution of residues on the β1α1 and β2α2 loops, and highlight the multiple roles that the β1α1 loop plays in IGPS catalysis. Thus, substitution of covarying residues in the active-site β1α1 and β2α2 loops of indole-3-glycerol phosphate synthase results in functional, structural, and dynamic changes, highlighting the multiple roles that the β1α1 loop plays in enzyme catalysis and the importance of regulating the structural dynamics of this loop through noncovalent

  18. Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron

    PubMed Central

    Schwalm, Nathan D.; Townsend, Guy E.

    2016-01-01

    ABSTRACT The utilization of simple sugars is widespread across all domains of life. In contrast, the breakdown of complex carbohydrates is restricted to a subset of organisms. A regulatory paradigm for integration of complex polysaccharide breakdown with simple sugar utilization was established in the mammalian gut symbiont Bacteroides thetaiotaomicron, whereby sensing of monomeric fructose regulates catabolism of both fructose and polymeric fructans. We now report that a different regulatory paradigm governs utilization of monomeric arabinose and the arabinose polymer arabinan. We establish that (i) arabinan utilization genes are controlled by a transcriptional activator that responds to arabinan and by a transcriptional repressor that responds to arabinose, (ii) arabinose utilization genes are regulated directly by the arabinose-responding repressor but indirectly by the arabinan-responding activator, and (iii) activation of both arabinan and arabinose utilization genes requires a pleiotropic transcriptional regulator necessary for survival in the mammalian gut. Genomic analysis predicts that this paradigm is broadly applicable to the breakdown of other polysaccharides in both B. thetaiotaomicron and other gut Bacteroides spp. The uncovered mechanism enables regulation of polysaccharide utilization genes in response to both the polysaccharide and its breakdown products. PMID:27729509

  19. Pesticides in stream sediment and aquatic biota: distribution, trends, and governing factors

    USGS Publications Warehouse

    Nowell, Lisa H.; Capel, Peter D.

    1999-01-01

    More than 20 years after the ban of DDT and other organochlorine pesticides, pesticides continue to be detected in air, rain, soil, surface water, bed sediment, and aquatic and terrestrial biota throughout the world. Recent research suggests that low levels of some of these pesticides may have the potential to affect the development, reproduction, and behavior of fish and wildlife, and possibly humans. Pesticides in Stream Sediment and Aquatic Biota: Distribution, Trends, and Governing Factors assesses the occurrence and behavior of pesticides in bed sediment and aquatic biota-the two major compartments of the hydrologic system where organochlorine pesticides are most likely to accumulate. This book collects, for the first time, results from several hundred monitoring studies and field experiments, ranging in scope from individual sites to the entire nation. Comprehensive tables provide concise summaries of study locations, pesticides analyzed, and study outcomes. Comprehensive and extensively illustrated, Pesticides in Stream Sediment and Aquatic Biota: Distribution, Trends, and Governing Factors evaluates the sources, environmental fate, geographic distribution, and long-term trends of pesticides in bed sediment and aquatic biota. The book focuses on organochlorine pesticides, but also assesses the potential for currently used pesticides to be found in bed sediment and aquatic biota. Topics covered in depth include the effect of land use on pesticide occurrence, mechanisms of pesticide uptake and accumulation by aquatic biota, and the environmental significance of observed levels of pesticides in stream sediment and aquatic biota.

  20. Processes and their explanatory factors governing distribution of organic phosphorous pools in lake sediments.

    PubMed

    Lü, Changwei; He, Jiang; Zuo, Le; Vogt, Rolf D; Zhu, Liang; Zhou, Bin; Mohr, Christian W; Guan, Rui; Wang, Weiying; Yan, Daohao

    2016-02-01

    The amount of organic phosphorus (OP) and its distribution among different pools in lake sediments depends on biotic and abiotic processes driving the OP fractionation. Key environmental factors governing these transformations processes between OP fractionations in sediments were studied on the basis of geochemical characteristics of OP pools in relation to environmental factors in the sediments. The results illustrate that the factors influencing the accumulation or depletion of different OP pools were intrinsically dependent on the composition of the deposited organic matter (OM). During the mineralization of the OM the microorganisms excrete the enzyme alkaline phosphatase, accelerating the OP hydrolysis, and thereby setting the grounds for the bacterially-mediated oxidation of OM. There are two main degradation products of the labile OP pool (LOP) and the moderately labile OP pool (MLOP): Either the OP is transformed to a dissolved organic or inorganic P form, and thereby released to water column, or OP is transformed to a non-labile OP pool and stored in the sediments. A comparative study showed that oxy-hydroxides of iron (Fe) and aluminum (Al) only played an important role in influencing OP fractionation in Lake Wuliangsuhai, while the complexation reactions of OP with calcium ions and sorption to its minerals are key factors governing the OP fractionation in the two alkaline lakes. It is worth noting that a significant correlation between the Fe-P pool and the pools of LOP and MLOP indicates that the degradation of the rather labile OP pools are highly dependent on the iron redox reaction. PMID:26688248

  1. Processes and their explanatory factors governing distribution of organic phosphorous pools in lake sediments.

    PubMed

    Lü, Changwei; He, Jiang; Zuo, Le; Vogt, Rolf D; Zhu, Liang; Zhou, Bin; Mohr, Christian W; Guan, Rui; Wang, Weiying; Yan, Daohao

    2016-02-01

    The amount of organic phosphorus (OP) and its distribution among different pools in lake sediments depends on biotic and abiotic processes driving the OP fractionation. Key environmental factors governing these transformations processes between OP fractionations in sediments were studied on the basis of geochemical characteristics of OP pools in relation to environmental factors in the sediments. The results illustrate that the factors influencing the accumulation or depletion of different OP pools were intrinsically dependent on the composition of the deposited organic matter (OM). During the mineralization of the OM the microorganisms excrete the enzyme alkaline phosphatase, accelerating the OP hydrolysis, and thereby setting the grounds for the bacterially-mediated oxidation of OM. There are two main degradation products of the labile OP pool (LOP) and the moderately labile OP pool (MLOP): Either the OP is transformed to a dissolved organic or inorganic P form, and thereby released to water column, or OP is transformed to a non-labile OP pool and stored in the sediments. A comparative study showed that oxy-hydroxides of iron (Fe) and aluminum (Al) only played an important role in influencing OP fractionation in Lake Wuliangsuhai, while the complexation reactions of OP with calcium ions and sorption to its minerals are key factors governing the OP fractionation in the two alkaline lakes. It is worth noting that a significant correlation between the Fe-P pool and the pools of LOP and MLOP indicates that the degradation of the rather labile OP pools are highly dependent on the iron redox reaction.

  2. Novel Drosophila receptor that binds multiple growth factors

    SciTech Connect

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-05-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10/sup -6/ to 10/sup -8/ M. The 100 kDa protein can be affinity-labeled with these /sup 125/I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by /sup 125/I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors.

  3. Probabilistic Inference of Transcription Factor Binding from Multiple Data Sources

    PubMed Central

    Lähdesmäki, Harri; Rust, Alistair G.; Shmulevich, Ilya

    2008-01-01

    An important problem in molecular biology is to build a complete understanding of transcriptional regulatory processes in the cell. We have developed a flexible, probabilistic framework to predict TF binding from multiple data sources that differs from the standard hypothesis testing (scanning) methods in several ways. Our probabilistic modeling framework estimates the probability of binding and, thus, naturally reflects our degree of belief in binding. Probabilistic modeling also allows for easy and systematic integration of our binding predictions into other probabilistic modeling methods, such as expression-based gene network inference. The method answers the question of whether the whole analyzed promoter has a binding site, but can also be extended to estimate the binding probability at each nucleotide position. Further, we introduce an extension to model combinatorial regulation by several TFs. Most importantly, the proposed methods can make principled probabilistic inference from multiple evidence sources, such as, multiple statistical models (motifs) of the TFs, evolutionary conservation, regulatory potential, CpG islands, nucleosome positioning, DNase hypersensitive sites, ChIP-chip binding segments and other (prior) sequence-based biological knowledge. We developed both a likelihood and a Bayesian method, where the latter is implemented with a Markov chain Monte Carlo algorithm. Results on a carefully constructed test set from the mouse genome demonstrate that principled data fusion can significantly improve the performance of TF binding prediction methods. We also applied the probabilistic modeling framework to all promoters in the mouse genome and the results indicate a sparse connectivity between transcriptional regulators and their target promoters. To facilitate analysis of other sequences and additional data, we have developed an on-line web tool, ProbTF, which implements our probabilistic TF binding prediction method using multiple data sources

  4. Physicochemical factors governing the performance of nedocromil sodium as a dry powder aerosol.

    PubMed

    Clarke, M J; Tobyn, M J; Staniforth, J N

    2000-09-01

    Previous investigations have found that the in vitro aerosol performance of nedocromil sodium is poor. A study has been undertaken to gain a better understanding of the physicochemical properties of the drug particles together with the factors governing the aerosol performance of inhalation systems containing this drug. Material previously passed through a hammer mill only and particles subsequently passed through a micronizer were characterized, and the information gathered was correlated with the in vitro aerosol performance of the pure drug systems. Optimization of particle sizing procedures revealed that both sets of materials were ultrafine powders with a volume median diameter of approximately 1 microm. It is concluded that the processing stages, employed in the manufacture of these batches of fine particle nedocromil sodium trihydrate, may not in fact be primary particle size reduction stages but instead deaggregation stages and that these govern the aerosol performance. The in vitro aerosol performance of samples of the "micronized" nedocromil sodium stored over a range of relative humidities (RHs) was characterized. Storage RHs in the range 12-76% (where nedocromil sodium is stable as the trihydrate) did not have a dramatic effect on the in vitro aerosol performance of the drug. However, conversion to the heptahemihydrate (following storage of the drug at 86% RH) significantly decreased the deaggregation performance in an in vitro model.

  5. Different Factors Govern Chlorination and Encapsulation in Fullerenes: The Case of C66.

    PubMed

    Alegret, Núria; Abella, Laura; Azmani, Khalid; Rodríguez-Fortea, Antonio; Poblet, Josep M

    2015-08-01

    C66 is one of the smallest fullerenes that is able to encapsulate more than one metal atom, as in Sc2@C66, as well as to get chlorinated at a low level, C66Cl10 or C66Cl6. We show here, with the help of computations at density functional theory level, that these two means of obtaining derivatives of non-isolated pentagon rule fullerenes are dictated by different factors. Chlorination takes place at temperatures lower than 2000 K, once the neutral fullerenes are formed. Encapsulation is, however, mainly governed by the charge transfer, although the Sc···Sc distance is also playing a role in the stability of Sc2@C66. PMID:26176335

  6. Occupational Stress and Cardiovascular Risk Factors in High-Ranking Government Officials and Office Workers

    PubMed Central

    Mirmohammadi, Seyyed Jalil; Taheri, Mahmoud; Mehrparvar, Amir Houshang; Heydari, Mohammad; Saadati Kanafi, Ali; Mostaghaci, Mehrdad

    2014-01-01

    Background: Cardiovascular diseases are among the most important sources of mortality and morbidity, and have a high disease burden. There are some major well-known risk factors, which contribute to the development of these diseases. Occupational stress is caused due to imbalance between job demands and individual’s ability, and it has been implicated as an etiology for cardiovascular diseases. Objectives: This study was conducted to evaluate the cardiovascular risk factors and different dimensions of occupational stress in high-ranking government officials, comparing an age and sex-matched group of office workers with them. Patients and Methods: We invited 90 high-ranking officials who managed the main governmental offices in a city, and 90 age and sex-matched office workers. The subjects were required to fill the occupational role questionnaire (Osipow) which evaluated their personal and medical history as well as occupational stress. Then, we performed physical examination and laboratory tests to check for cardiovascular risk factors. Finally, the frequency of cardiovascular risk factors and occupational stress of two groups were compared. Results: High-ranking officials in our study had less work experience in their current jobs and smoked fewer pack-years of cigarette, but they had higher waist and hip circumference, higher triglyceride level, more stress from role overload and responsibility, and higher total stress score. Our group of office workers had more occupational stress because of role ambiguity and insufficiency, but their overall job stress was less than officials. Conclusions: The officials have higher scores in some dimensions of occupational stress and higher overall stress score. Some cardiovascular risk factors were also more frequent in managers. PMID:25389469

  7. Investigation of Multiple Human Factors in Personalized Learning

    ERIC Educational Resources Information Center

    Chen, Sherry Y.; Huang, Pei-Ren; Shih, Yu-Cheng; Chang, Li-Ping

    2016-01-01

    In the past decade, a number of personalized learning systems have been developed and they mainly focus on learners' prior knowledge. On the other hand, previous research suggested that gender differences and cognitive styles have great effects on student learning. To this end, this study examines how human factors, especially gender differences…

  8. RepA-WH1 prionoid: Clues from bacteria on factors governing phase transitions in amyloidogenesis.

    PubMed

    Giraldo, Rafael; Fernández, Cristina; Moreno-del Álamo, María; Molina-García, Laura; Revilla-García, Aída; Sánchez-Martínez, María Cruz; Giménez-Abián, Juan F; Moreno-Díaz de la Espina, Susana

    2016-01-01

    In bacterial plasmids, Rep proteins initiate DNA replication by undergoing a structural transformation coupled to dimer dissociation. Amyloidogenesis of the 'winged-helix' N-terminal domain of RepA (WH1) is triggered in vitro upon binding to plasmid-specific DNA sequences, and occurs at the bacterial nucleoid in vivo. Amyloid fibers are made of distorted RepA-WH1 monomers that assemble as single or double intertwined tubular protofilaments. RepA-WH1 causes in E. coli an amyloid proteinopathy, which is transmissible from mother to daughter cells, but not infectious, and enables conformational imprinting in vitro and in vivo; i.e. RepA-WH1 is a 'prionoid'. Microfluidics allow the assessment of the intracellular dynamics of RepA-WH1: bacterial lineages maintain two types (strains-like) of RepA-WH1 amyloids, either multiple compact cytotoxic particles or a single aggregate with the appearance of a fluidized hydrogel that it is mildly detrimental to growth. The Hsp70 chaperone DnaK governs the phase transition between both types of RepA-WH1 aggregates in vivo, thus modulating the vertical propagation of the prionoid. Engineering chimeras between the Sup35p/[PSI(+)] prion and RepA-WH1 generates [REP-PSI(+)], a synthetic prion exhibiting strong and weak phenotypic variants in yeast. These recent findings on a synthetic, self-contained bacterial prionoid illuminate central issues of protein amyloidogenesis. PMID:27040981

  9. RepA-WH1 prionoid: Clues from bacteria on factors governing phase transitions in amyloidogenesis

    PubMed Central

    Giraldo, Rafael; Fernández, Cristina; Moreno-del Álamo, María; Molina-García, Laura; Revilla-García, Aída; Sánchez-Martínez, María Cruz; Giménez-Abián, Juan F.; Moreno-Díaz de la Espina, Susana

    2016-01-01

    ABSTRACT In bacterial plasmids, Rep proteins initiate DNA replication by undergoing a structural transformation coupled to dimer dissociation. Amyloidogenesis of the ‘winged-helix’ N-terminal domain of RepA (WH1) is triggered in vitro upon binding to plasmid-specific DNA sequences, and occurs at the bacterial nucleoid in vivo. Amyloid fibers are made of distorted RepA-WH1 monomers that assemble as single or double intertwined tubular protofilaments. RepA-WH1 causes in E. coli an amyloid proteinopathy, which is transmissible from mother to daughter cells, but not infectious, and enables conformational imprinting in vitro and in vivo; i.e. RepA-WH1 is a ‘prionoid’. Microfluidics allow the assessment of the intracellular dynamics of RepA-WH1: bacterial lineages maintain two types (strains-like) of RepA-WH1 amyloids, either multiple compact cytotoxic particles or a single aggregate with the appearance of a fluidized hydrogel that it is mildly detrimental to growth. The Hsp70 chaperone DnaK governs the phase transition between both types of RepA-WH1 aggregates in vivo, thus modulating the vertical propagation of the prionoid. Engineering chimeras between the Sup35p/[PSI+] prion and RepA-WH1 generates [REP-PSI+], a synthetic prion exhibiting strong and weak phenotypic variants in yeast. These recent findings on a synthetic, self-contained bacterial prionoid illuminate central issues of protein amyloidogenesis. PMID:27040981

  10. Multiple optimal learning factors for feed-forward networks

    NASA Astrophysics Data System (ADS)

    Malalur, Sanjeev S.; Manry, Michael T.

    2010-04-01

    A batch training algorithm for feed-forward networks is proposed which uses Newton's method to estimate a vector of optimal learning factors, one for each hidden unit. Backpropagation, using this learning factor vector, is used to modify the hidden unit's input weights. Linear equations are then solved for the network's output weights. Elements of the new method's Gauss-Newton Hessian matrix are shown to be weighted sums of elements from the total network's Hessian. In several examples, the new method performs better than backpropagation and conjugate gradient, with similar numbers of required multiplies. The method performs as well as or better than Levenberg-Marquardt, with several orders of magnitude fewer multiplies due to the small size of its Hessian.

  11. Impact of Multiple Factors on the Degree of Tinnitus Distress

    PubMed Central

    Brüggemann, Petra; Szczepek, Agnieszka J.; Rose, Matthias; McKenna, Laurence; Olze, Heidi; Mazurek, Birgit

    2016-01-01

    Objective: The primary cause of subjective tinnitus is a dysfunction of the auditory system; however, the degree of distress tinnitus causes depends largely on the psychological status of the patient. Our goal was to attempt to associate the grade of tinnitus-related distress with the psychological distress, physical, or psychological discomfort patients experienced, as well as potentially relevant social parameters, through a simultaneous analysis of these factors. Methods: We determined the level of tinnitus-related distress in 531 tinnitus patients using the German version of the tinnitus questionnaire (TQ). In addition, we used the Perceived Stress Questionnaire (PSQ); General Depression Scale Allgemeine Depression Skala (ADS), Berlin Mood Questionnaire (BSF); somatic symptoms inventory (BI), and SF-8 health survey as well as general information collected through a medical history. Results: The TQ score significantly correlated with a score obtained using PSQ, ADS, BSF, BI, and SF-8 alongside psychosocial factors such as age, gender, and marital status. The level of hearing loss and the auditory properties of the specific tinnitus combined with perceived stress and the degree of depressive mood and somatic discomfort of a patient were identified as medium-strong predictors of chronic tinnitus. Social factors such as gender, age, or marital status also had an impact on the degree of tinnitus distress. The results that were obtained were implemented in a specific cortical distress network model. Conclusions: Using a large representative sample of patients with chronic tinnitus permitted a simultaneous statistical measurement of psychometric and audiological parameters in predicting tinnitus distress. We demonstrate that single factors can be distinguished in a manner that explains their causative association and influence on the induction of tinnitus-related distress. PMID:27445776

  12. Homeobox transcription factor Six7 governs expression of green opsin genes in zebrafish.

    PubMed

    Ogawa, Yohey; Shiraki, Tomoya; Kojima, Daisuke; Fukada, Yoshitaka

    2015-08-01

    Colour discrimination in vertebrates requires cone photoreceptor cells in the retina, and high-acuity colour vision is endowed by a set of four cone subtypes expressing UV-, blue-, green- and red-sensitive opsins. Previous studies identified transcription factors governing cone photoreceptor development in mice, although loss of blue and green opsin genes in the evolution of mammals make it difficult to understand how high-acuity colour vision was organized during evolution and development. Zebrafish (Danio rerio) represents a valuable vertebrate model for studying colour vision as it retains all the four ancestral vertebrate cone subtypes. Here, by RT-qPCR and in situ hybridization analysis, we found that sine oculis homeobox homolog 7 (six7), a transcription factor widely conserved in ray-finned fish, is expressed predominantly in the cone photoreceptors in zebrafish at both the larval and the adult stages. TAL effector nuclease-based six7 knock-out revealed its roles in expression of green, red and blue cone opsin genes. Most prominently, the six7 deficiency caused a loss of expression of all the green opsins at both the larval and adult stages. six7 is indispensable for the development and/or maintenance of the green cones. PMID:26180064

  13. Factors Governing the Impact of Emerged Salt Diapirs on Water Resources.

    PubMed

    Zarei, M

    2016-05-01

    Salt diapirs in southern Iran are typically in contact with karstic and alluvial aquifers and consequently they are the most likely sources of groundwater salinization in this arid region. However, there are some salt diapirs that have no significant degradation effect on adjacent aquifers. Assessments of 62 of 122 Iranian-emerged salt diapirs based on geological, geomorphological, hydrogeological, and hydrochemical investigations indicated that 45% of the studied salt diapirs did not have a negative impact on surrounding water resources, whereas 55% of the salt diapirs have degraded water quality of adjacent aquifers. The impacts ranged from low- to high-grade salinization. We characterize here four major factors that control the impact of salt diapirs on surrounding water resources: (1) the evolutionary stage of the diapir, (2) the geological and (3) hydrogeological setting of the diapir, and (4) human activities. Identification of the major factors governing the influence of salt diapirs on the adjacent aquifers is necessary to understand the mechanism of salt diapir impact on adjacent aquifers, and subsequently to decide how to mitigate the deteriorating effect of the diapirs on the surrounding water resources. PMID:26394154

  14. Factors Governing the Impact of Emerged Salt Diapirs on Water Resources.

    PubMed

    Zarei, M

    2016-05-01

    Salt diapirs in southern Iran are typically in contact with karstic and alluvial aquifers and consequently they are the most likely sources of groundwater salinization in this arid region. However, there are some salt diapirs that have no significant degradation effect on adjacent aquifers. Assessments of 62 of 122 Iranian-emerged salt diapirs based on geological, geomorphological, hydrogeological, and hydrochemical investigations indicated that 45% of the studied salt diapirs did not have a negative impact on surrounding water resources, whereas 55% of the salt diapirs have degraded water quality of adjacent aquifers. The impacts ranged from low- to high-grade salinization. We characterize here four major factors that control the impact of salt diapirs on surrounding water resources: (1) the evolutionary stage of the diapir, (2) the geological and (3) hydrogeological setting of the diapir, and (4) human activities. Identification of the major factors governing the influence of salt diapirs on the adjacent aquifers is necessary to understand the mechanism of salt diapir impact on adjacent aquifers, and subsequently to decide how to mitigate the deteriorating effect of the diapirs on the surrounding water resources.

  15. Homeobox transcription factor Six7 governs expression of green opsin genes in zebrafish.

    PubMed

    Ogawa, Yohey; Shiraki, Tomoya; Kojima, Daisuke; Fukada, Yoshitaka

    2015-08-01

    Colour discrimination in vertebrates requires cone photoreceptor cells in the retina, and high-acuity colour vision is endowed by a set of four cone subtypes expressing UV-, blue-, green- and red-sensitive opsins. Previous studies identified transcription factors governing cone photoreceptor development in mice, although loss of blue and green opsin genes in the evolution of mammals make it difficult to understand how high-acuity colour vision was organized during evolution and development. Zebrafish (Danio rerio) represents a valuable vertebrate model for studying colour vision as it retains all the four ancestral vertebrate cone subtypes. Here, by RT-qPCR and in situ hybridization analysis, we found that sine oculis homeobox homolog 7 (six7), a transcription factor widely conserved in ray-finned fish, is expressed predominantly in the cone photoreceptors in zebrafish at both the larval and the adult stages. TAL effector nuclease-based six7 knock-out revealed its roles in expression of green, red and blue cone opsin genes. Most prominently, the six7 deficiency caused a loss of expression of all the green opsins at both the larval and adult stages. six7 is indispensable for the development and/or maintenance of the green cones.

  16. Homeobox transcription factor Six7 governs expression of green opsin genes in zebrafish

    PubMed Central

    Ogawa, Yohey; Shiraki, Tomoya; Kojima, Daisuke; Fukada, Yoshitaka

    2015-01-01

    Colour discrimination in vertebrates requires cone photoreceptor cells in the retina, and high-acuity colour vision is endowed by a set of four cone subtypes expressing UV-, blue-, green- and red-sensitive opsins. Previous studies identified transcription factors governing cone photoreceptor development in mice, although loss of blue and green opsin genes in the evolution of mammals make it difficult to understand how high-acuity colour vision was organized during evolution and development. Zebrafish (Danio rerio) represents a valuable vertebrate model for studying colour vision as it retains all the four ancestral vertebrate cone subtypes. Here, by RT-qPCR and in situ hybridization analysis, we found that sine oculis homeobox homolog 7 (six7), a transcription factor widely conserved in ray-finned fish, is expressed predominantly in the cone photoreceptors in zebrafish at both the larval and the adult stages. TAL effector nuclease-based six7 knock-out revealed its roles in expression of green, red and blue cone opsin genes. Most prominently, the six7 deficiency caused a loss of expression of all the green opsins at both the larval and adult stages. six7 is indispensable for the development and/or maintenance of the green cones. PMID:26180064

  17. Complete effect-profile assessment in association studies with multiple genetic and multiple environmental factors.

    PubMed

    Wang, Zhi; Maity, Arnab; Luo, Yiwen; Neely, Megan L; Tzeng, Jung-Ying

    2015-02-01

    Studying complex diseases in the post genome-wide association studies (GWAS) era has led to developing methods that consider factor-sets rather than individual genetic/environmental factors (i.e., Multi-G-Multi-E studies), and mining for potential gene-environment (G×E) interactions has proven to be an invaluable aid in both discovery and deciphering underlying biological mechanisms. Current approaches for examining effect profiles in Multi-G-Multi-E analyses are either underpowered due to large degrees of freedom, ill-suited for detecting G×E interactions due to imprecise modeling of the G and E effects, or lack of capacity for modeling interactions between two factor-sets (e.g., existing methods focus primarily on a single E factor). In this work, we illustrate the issues encountered in constructing kernels for investigating interactions between two factor-sets, and propose a simple yet intuitive solution to construct the G×E kernel that retains the ease-of-interpretation of classic regression. We also construct a series of kernel machine (KM) score tests to evaluate the complete effect profile (i.e., the G, E, and G×E effects individually or in combination). We show, via simulations and a data application, that the proposed KM methods outperform the classic and PC regressions across a range of scenarios, including varying effect size, effect structure, and interaction complexity. The largest power gain was observed when the underlying effect structure involved complex G×E interactions; however, the proposed methods have consistent, powerful performance when the effect profile is simple or complex, suggesting that the proposed method could be a useful tool for exploratory or confirmatory G×E analysis.

  18. Complete Effect-Profile Assessment in Association Studies with Multiple Genetic and Multiple Environmental Factors

    PubMed Central

    Wang, Zhi; Maity, Arnab; Luo, Yiwen; Neely, Megan L.; Tzeng, Jung-Ying

    2014-01-01

    Studying complex diseases in the post GWAS era has led to developing methods that consider factor-sets rather than individual genetic/environmental factors (i.e., Multi-G-Multi-E studies), and mining for potential gene-environment (GxE) interactions has proven to be an invaluable aid in both discovery and deciphering underlying biological mechanisms. Current approaches for examining effect profiles in Multi-G-Multi-E analyses are either underpowered due to large degrees of freedom, ill-suited for detecting GxE interactions due to imprecise modeling of the G and E effects, or lack of capacity for modeling interactions between two factor sets (e.g., existing methods focus primarily on a single E factor). In this work, we illustrate the issues encountered in constructing kernels for investigating interactions between two factor-sets, and propose a simple yet intuitive solution to construct the GxE kernel that retains the ease-of-interpretation of classic regression. We also construct a series of KM score tests to evaluate the complete effect profile (i.e., the G, E, and GxE effects individually or in combination). We show, via simulations and a data application, that the proposed KM methods outperform the classic and PC regressions across a range of scenarios, including varying effect size, effect structure, and interaction complexity. The largest power gain was observed when the underlying effect structure involved complex GxE interactions; however, the proposed methods have consistent, powerful performance when the effect profile is simple or complex, suggesting that the proposed method could be a useful tool for exploratory or confirmatory GxE analysis. PMID:25538034

  19. Factors governing particle number emissions in a waste-to-energy plant.

    PubMed

    Ozgen, Senem; Cernuschi, Stefano; Giugliano, Michele

    2015-05-01

    Particle number concentration and size distribution measurements were performed on the stack gas of a waste-to-energy plant which co-incinerates municipal solid waste, sewage sludge and clinical waste in two lines. Average total number of particles was found to be 4.0·10(5)cm(-3) and 1.9·10(5)cm(-3) for the line equipped with a wet flue gas cleaning process and a dry cleaning system, respectively. Ultrafine particles (dp<100nm) accounted for about 97% of total number concentration for both lines, whereas the nanoparticle (dp<50nm) contribution differed slightly between the lines (87% and 84%). The experimental data is explored statistically through some multivariate pattern identifying methods such as factor analysis and cluster analysis to help the interpretation of the results regarding the origin of the particles in the flue gas with the objective of determining the factors governing the particle number emissions. The higher moisture of the flue gas in the wet cleaning process was found to increase the particle number emissions on average by a factor of about 2 due to increased secondary formation of nanoparticles through nucleation of gaseous precursors such as sulfuric acid, ammonia and water. The influence of flue gas dilution and cooling monitored through the variation of the sampling conditions also confirms the potential effect of the secondary new particle formation in increasing the particle number emissions. This finding shows the importance of reporting the experimental conditions in detail to enable the comparison and interpretation of particle number emissions. Regarding the fuel characteristics no difference was observed in terms of particle number concentration and size distributions between the clinical waste feed and the municipal solid waste co-incineration with sludge.

  20. Multiple Weather Factors Affect Apparent Survival of European Passerine Birds

    PubMed Central

    Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  1. Multiple weather factors affect apparent survival of European passerine birds.

    PubMed

    Salewski, Volker; Hochachka, Wesley M; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  2. Single and Multiple Suicide Attempts and Associated Health Risk Factors in New Hampshire Adolescents

    ERIC Educational Resources Information Center

    Rosenberg, Harriet J.; Jankowski, Mary K.; Sengupta, Anjana; Wolfe, Rosemarie S.; Wolford, George L., II; Rosenberg, Stanley D.

    2005-01-01

    In this study we examined self-reported suicide attempts and their relationship to other health risk factors in a community sample of 16,644 adolescents. Fifteen percent endorsed suicide attempts (10% single; 5% multiple attempts). We hypothesized that multiple attempters would show higher prevalence of comorbid health risks than single or…

  3. Factors Governing the Germination of Sulfate-Reducing Desulfotomaculum Endospores Involved in Oil Reservoir Souring.

    NASA Astrophysics Data System (ADS)

    Sherry, A.; Bell, E.; Cueto, G.; Suarez-Suarez, A.; Pilloni, G.; Hubert, C. R.

    2015-12-01

    Reservoir souring is caused by the activity of sulfate-reducing microorganisms (SRM) in subsurface oil reservoirs, and is often induced by seawater injection during secondary oil recovery. Souring can potentially contribute to corrosion of infrastructure, health and safety hazards to the workforce, and reduction in value by increasing refining costs associated with producing the oil resource. Souring causes annual losses in the billions of dollars to the oil industry. Endospore-forming SRM, such as Desulfotomaculum spp., are often suspected culprits in reservoir souring. Endospores can survive unfavourable conditions for long periods, yet remain poised to germinate and become active if conditions become more favourable. Factors governing endospore germination are poorly understood, but are thought to include availability of nutrients, possibly metabolic by products of other anaerobic bioprocesses, and/or variations in temperature. Most research has focused on aerobic Bacillus spp., with very few studies dedicated to spore germination among anaerobes (order Clostridiales) including the sulfate-reducing Desulfotomaculum found in anoxic subsurface petroleum reservoirs. For Desulfotomaculum spores in deep hot oil reservoirs, cold seawater introduction during secondary oil recovery may create thermal viability zones for sulfate reduction near the injection wellbore. To evaluate these processes, sulfate-containing microcosms were prepared with different marine sediments as a source of spores, and amended with organic substrates in the presence or absence of oil. Incubation at 80°C for six days was followed by a down-shift in temperature to 60°C to mimic cold seawater injection into a hot reservoir. Souring did not occur at 80°C, but commenced within hours at 60°C. Microcosms were monitored for sulfate reduction and organic acids in combination with next generation sequencing of 16S rRNA genes (Ion Torrent, Illumina MiSeq). Through a combination of high

  4. The Association between Vascular Endothelial Growth Factor-related Factors with Severity of Multiple Sclerosis.

    PubMed

    Kouchaki, Ebrahim; Otroshi Shahreza, Bentolhoda; Faraji, Saiedeh; Nikoueinejad, Hassan; Sehat, Mojtaba

    2016-06-01

    Previous studies have demonstrated that vascular endothelial growth factor (VEGF) can trigger angiogenesis as well as inflammation through binding to its membranous receptor-1 on endothelial and inflammatory cells. We aimed to correlate the circulatory number of cells expressing such receptor as well as the serum level of VEGF and the soluble form of its receptor-1 (sVEGFR1) to the severity of multiple sclerosis (MS). This case-control study was done on 102 cases of MS lacking any other inflammatory or pathologic conditions and 75 healthy volunteer subjects. The severity of MS was examined by expanded disability status scale (EDSS). The serum levels of VEGF and sVEGFR1 were measured by ELISA, and the circulatory frequency of VEGFR1 expressing cells was counted by flowcytometry. Then, the correlation of these variables was evaluated by pearson's correlation coefficient and spearman's test. We also investigated the influence of sex, age, treatment duration, and the number of recurrences on such association through linear multivariate regression method. We found an increase in circulatory level of VEGFR1 expressing cells and the serum level of VEGF as well as sVEGFR1 in MS patients compared to healthy controls (p<0.001). The greater severity of MS, the higher VEGFR1 expressing cells (ρ=0.47; p<0.001), serum level of VEGF (ρ=0.44; p<0.001), and sVEGFR1 (ρ=0.76; p<0.001). Having adjusted the effects of VEGF on sVEGFR1, we found a significant association between the EDSS score and sVEGFR1 (β=0.007; p<0.001). Our findings revealed that circulatory membranous as well as soluble expression of VEGFR1 increases during angiogenic and inflammatory phenomena of MS. Such increase may exacerbate the symptoms and cause more disability. PMID:27424135

  5. Multiple genetic factors in the heterogeneity of thyroid hormone resistance

    SciTech Connect

    Weiss, R.E.; Refetoff, S. ); Marcocci, C.; Bruno-Bossio, G. )

    1993-01-01

    Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T[sub 3]-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TR[beta] mutations have been reported. The authors compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T[sub 3]-binding domain of TR[beta]; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TR[beta] mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T[sub 4] and T[sub 3], and rT[sub 3] levels were significantly higher in Group A vs Groups B and C. However, with the exception of T[sub 3], the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR[beta] mutations. 23 refs., 2 figs., 1 tab.

  6. Molecular and Physicochemical Factors Governing Solubility of the HIV gp41 Ectodomain.

    PubMed

    Manssour-Triedo, Fadia; Crespillo, Sara; Morel, Bertrand; Casares, Salvador; Mateo, Pedro L; Notka, Frank; Roger, Marie G; Mouz, Nicolas; El-Habib, Raphaelle; Conejero-Lara, Francisco

    2016-08-23

    The HIV gp41 ectodomain (e-gp41) is an attractive target for the development of vaccines and drugs against HIV because of its crucial role in viral fusion to the host cell. However, because of the high insolubility of e-gp41, most biophysical and structural analyses have relied on the production of truncated versions removing the loop region of gp41 or the utilization of nonphysiological solubilizing conditions. The loop region of gp41 is also known as principal immunodominant domain (PID) because of its high immunogenicity, and it is essential for gp41-mediated HIV fusion. In this study we identify the aggregation-prone regions of the amino acid sequence of the PID and engineer a highly soluble mutant that preserves the trimeric structure of the wild-type e-gp41 under physiological pH. Furthermore, using a reverse mutagenesis approach, we analyze the role of mutated amino acids upon the physicochemical factors that govern solubility of e-gp41. On this basis, we propose a molecular model for e-gp41 self-association, which can guide the production of soluble e-gp41 mutants for future biophysical analyses and biotechnological applications. PMID:27558714

  7. Factors to Govern Soluble and Insoluble Aggregate-formation in Monoclonal Antibodies.

    PubMed

    Fukuda, Jun; Iwura, Takafumi; Yanagihara, Shigehiro; Kano, Kenji

    2015-01-01

    The aggregation formation of monoclonal antibodies as biopharmaceuticals induced by heat stress was evaluated by size-exclusion chromatography, and the formation rate was correlated with several physicochemical parameters of the antibodies to clarify the factors to govern the aggregate formation. The parameters we studied were: the melting temperature (Tm) and the standard enthalpy of the melting point (ΔmH°) evaluated by differential scanning calorimetry under given and common conditions; the wavelength (λmax) and the intensity (Fint) of the maximum fluorescence peak of 1-anilinonaphthalene-8-sulfonate as a probe dye; the z-average diameter (D) evaluated by dynamic light scattering; and the isoelectric point (pI) and the hydrophobic index (Hpho) of the complementarity determining region calculated from the amino acid sequence. Multivariate statistical analysis with these explanatory variables based on Akaike's information criterion indicates that the soluble aggregate formation is negatively correlated with Tm and pI, while the insoluble aggregate formation is positively correlated with Fint and pI. Based on these results, the mechanisms of the aggregate formation and methods to prevent the formation are discussed.

  8. Crepuscular flight activity of an invasive insect governed by interacting abiotic factors.

    PubMed

    Chen, Yigen; Seybold, Steven J

    2014-01-01

    Seasonal and diurnal flight patterns of the invasive walnut twig beetle, Pityophthorus juglandis, were assessed between 2011 and 2014 in northern California, USA in the context of the effects of ambient temperature, light intensity, wind speed, and barometric pressure. Pityophthorus juglandis generally initiated flight in late January and continued until late November. This seasonal flight could be divided approximately into three phases (emergence: January-March; primary flight: May-July; and secondary flight: September-October). The seasonal flight response to the male-produced aggregation pheromone was consistently female-biased (mean of 58.9% females). Diurnal flight followed a bimodal pattern with a minor peak in mid-morning and a major peak at dusk (76.4% caught between 1800 and 2200 h). The primarily crepuscular flight activity had a Gaussian relationship with ambient temperature and barometric pressure but a negative exponential relationship with increasing light intensity and wind speed. A model selection procedure indicated that the four abiotic factors collectively and interactively governed P. juglandis diurnal flight. For both sexes, flight peaked under the following second-order interactions among the factors when: 1) temperature between was 25 and 30 °C and light intensity was less than 2000 lux; 2) temperature was between 25 and 35 °C and barometric pressure was between 752 and 762 mba (and declined otherwise); 3) barometric pressure was between 755 and 761 mba and light intensity was less than 2000 lux (and declined otherwise); and 4) temperature was ca. 30 °C and wind speed was ca. 2 km/h. Thus, crepuscular flight activity of this insect can be best explained by the coincidence of moderately high temperature, low light intensity, moderate wind speed, and low to moderate barometric pressure. The new knowledge provides physical and temporal guidelines for the application of semiochemical-based control techniques as part of an IPM program for this

  9. Peak Stress Intensity Factor Governs Crack Propagation Velocity In Crosslinked UHMWPE

    PubMed Central

    Sirimamilla, P. Abhiram; Furmanski, Jevan; Rimnac, Clare

    2013-01-01

    Ultra high molecular weight polyethylene (UHMWPE) has been successfully used as a bearing material in total joint replacement components. However, these bearing materials can fail as a result of in vivo static and cyclic loads. Crack propagation behavior in this material has been considered using the Paris relationship which relates fatigue crack growth rate, da/dN (mm/cycle) versus the stress intensity factor range, ΔK (Kmax-Kmin, MPa√m). However, recent work suggests that the crack propagation velocity of conventional UHMWPE is driven by the peak stress intensity (Kmax), not ΔK. The hypothesis of this study is that the crack propagation velocity of highly crosslinked and remelted UHMWPE is also driven by the peak stress intensity, Kmax, during cyclic loading, rather than by ΔK. To test this hypothesis, two highly crosslinked (65 kGy and 100 kGy) and remelted UHMWPE materials were examined. Frequency, waveform and R-ratio were varied between test conditions to determine the governing factor for fatigue crack propagation. It was found that the crack propagation velocity in crosslinked UHMWPE is also driven by Kmax and not ΔK, and is dependent on loading waveform and frequency in a predictable quasi-static manner. The current study supports that crack growth in crosslinked UHMWPE materials, even under cyclic loading conditions, can be described by a relationship between the velocity of crack growth, da/dt and the peak stress intensity, Kmax. The findings suggest that stable crack propagation can occur as a result of static loading only and this should be taken into consideration in design of UHMWPE total joint replacement components. PMID:23165898

  10. Peak stress intensity factor governs crack propagation velocity in crosslinked ultrahigh-molecular-weight polyethylene.

    PubMed

    Sirimamilla, Abhiram; Furmanski, Jevan; Rimnac, Clare

    2013-04-01

    Ultrahigh-molecular-weight polyethylene (UHMWPE) has been successfully used as a bearing material in total joint replacement components. However, these bearing materials can fail as a result of in vivo static and cyclic loads. Crack propagation behavior in this material has been considered using the Paris relationship which relates fatigue crack growth rate, da/dN (mm/cycle) versus the stress intensity factor range, ΔK (Kmax - Kmin , MPa√m). However, recent work suggests that the crack propagation velocity of conventional UHMWPE is driven by the peak stress intensity (Kmax ), not ΔK. The hypothesis of this study is that the crack propagation velocity of highly crosslinked and remelted UHMWPE is also driven by the peak stress intensity, Kmax , during cyclic loading. To test this hypothesis, two highly crosslinked (65 kGy and 100 kGy) and remelted UHMWPE materials were examined. Frequency, waveform, and R-ratio were varied between test conditions to determine the governing factor for fatigue crack propagation. It was found that the crack propagation velocity in crosslinked UHMWPE is also driven by Kmax and not ΔK, and is dependent on loading waveform and frequency in a predictable quasistatic manner. This study supports that crack growth in crosslinked UHMWPE materials, even under cyclic loading conditions, can be described by a relationship between the velocity of crack growth, da/dt and the peak stress intensity, Kmax . The findings suggest that stable crack propagation can occur as a result of static loading only and this should be taken into consideration in design of UHMWPE total joint replacement components.

  11. Crepuscular Flight Activity of an Invasive Insect Governed by Interacting Abiotic Factors

    PubMed Central

    Chen, Yigen; Seybold, Steven J.

    2014-01-01

    Seasonal and diurnal flight patterns of the invasive walnut twig beetle, Pityophthorus juglandis, were assessed between 2011 and 2014 in northern California, USA in the context of the effects of ambient temperature, light intensity, wind speed, and barometric pressure. Pityophthorus juglandis generally initiated flight in late January and continued until late November. This seasonal flight could be divided approximately into three phases (emergence: January–March; primary flight: May–July; and secondary flight: September–October). The seasonal flight response to the male-produced aggregation pheromone was consistently female-biased (mean of 58.9% females). Diurnal flight followed a bimodal pattern with a minor peak in mid-morning and a major peak at dusk (76.4% caught between 1800 and 2200 h). The primarily crepuscular flight activity had a Gaussian relationship with ambient temperature and barometric pressure but a negative exponential relationship with increasing light intensity and wind speed. A model selection procedure indicated that the four abiotic factors collectively and interactively governed P. juglandis diurnal flight. For both sexes, flight peaked under the following second-order interactions among the factors when: 1) temperature between was 25 and 30°C and light intensity was less than 2000 lux; 2) temperature was between 25 and 35°C and barometric pressure was between 752 and 762 mba (and declined otherwise); 3) barometric pressure was between 755 and 761 mba and light intensity was less than 2000 lux (and declined otherwise); and 4) temperature was ca. 30°C and wind speed was ca. 2 km/h. Thus, crepuscular flight activity of this insect can be best explained by the coincidence of moderately high temperature, low light intensity, moderate wind speed, and low to moderate barometric pressure. The new knowledge provides physical and temporal guidelines for the application of semiochemical-based control techniques as part of an IPM program for

  12. Crepuscular flight activity of an invasive insect governed by interacting abiotic factors.

    PubMed

    Chen, Yigen; Seybold, Steven J

    2014-01-01

    Seasonal and diurnal flight patterns of the invasive walnut twig beetle, Pityophthorus juglandis, were assessed between 2011 and 2014 in northern California, USA in the context of the effects of ambient temperature, light intensity, wind speed, and barometric pressure. Pityophthorus juglandis generally initiated flight in late January and continued until late November. This seasonal flight could be divided approximately into three phases (emergence: January-March; primary flight: May-July; and secondary flight: September-October). The seasonal flight response to the male-produced aggregation pheromone was consistently female-biased (mean of 58.9% females). Diurnal flight followed a bimodal pattern with a minor peak in mid-morning and a major peak at dusk (76.4% caught between 1800 and 2200 h). The primarily crepuscular flight activity had a Gaussian relationship with ambient temperature and barometric pressure but a negative exponential relationship with increasing light intensity and wind speed. A model selection procedure indicated that the four abiotic factors collectively and interactively governed P. juglandis diurnal flight. For both sexes, flight peaked under the following second-order interactions among the factors when: 1) temperature between was 25 and 30 °C and light intensity was less than 2000 lux; 2) temperature was between 25 and 35 °C and barometric pressure was between 752 and 762 mba (and declined otherwise); 3) barometric pressure was between 755 and 761 mba and light intensity was less than 2000 lux (and declined otherwise); and 4) temperature was ca. 30 °C and wind speed was ca. 2 km/h. Thus, crepuscular flight activity of this insect can be best explained by the coincidence of moderately high temperature, low light intensity, moderate wind speed, and low to moderate barometric pressure. The new knowledge provides physical and temporal guidelines for the application of semiochemical-based control techniques as part of an IPM program for this

  13. Factors Influencing the Selection of the Systems Integration Organizational Model Type for Planning and Implementing Government High-Technology Programs

    NASA Technical Reports Server (NTRS)

    Thomas, Leann; Utley, Dawn

    2006-01-01

    While there has been extensive research in defining project organizational structures for traditional projects, little research exists to support high technology government project s organizational structure definition. High-Technology Government projects differ from traditional projects in that they are non-profit, span across Government-Industry organizations, typically require significant integration effort, and are strongly susceptible to a volatile external environment. Systems Integration implementation has been identified as a major contributor to both project success and failure. The literature research bridges program management organizational planning, systems integration, organizational theory, and independent project reports, in order to assess Systems Integration (SI) organizational structure selection for improving the high-technology government project s probability of success. This paper will describe the methodology used to 1) Identify and assess SI organizational structures and their success rate, and 2) Identify key factors to be used in the selection of these SI organizational structures during the acquisition strategy process.

  14. Tumor necrosis factor alpha gene -376 polymorphism and susceptibility to multiple sclerosis: an Egyptian study.

    PubMed

    Nada, Mona Abd el Fattah; Labib, Dalia Ahmed

    2011-03-01

    Tumor necrosis factor alpha, a proinflammatory cytokine, plays an important role in the clinical activity of relapsing-remitting multiple sclerosis and the development of progression. Dysregulation in the expression of tumor necrosis factor gene had been suggested in the pathogenesis of multiple sclerosis. Our aim was to investigate the relationship between tumor necrosis factor α-376 polymorphism with disease susceptibility and course of multiple sclerosis in Egyptian patients. Polymerase chain reaction and restriction fragment length polymorphism were carried out on 36 primary progressive multiple sclerosis patients, 36 age- and sex-matched remitting relapsing multiple sclerosis patients (diagnosed according to McDonald's Diagnostic criteria) and 30 age- and sex-matched healthy controls. The GG genotype and the guanine allele (G) were detected significantly more often in the primary progressive (p = 0.02; p = 0.004, respectively) and remitting relapsing (p = 0.015; p = 0.024, respectively) multiple sclerosis groups as compared with the healthy control group. The G allele in the examined position in tumor necrosis factor alpha might have a role as regards susceptibility in both remitting relapsing and primary progressive multiple sclerosis.

  15. Protective Factors Associated with Fewer Multiple Problem Behaviors among Homeless/Runaway Youth

    ERIC Educational Resources Information Center

    Lightfoot, Marguerita; Stein, Judith A.; Tevendale, Heather; Preston, Kathleen

    2011-01-01

    Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls;…

  16. Science Teaching Efficacy of Preservice Elementary Teachers: Examination of the Multiple Factors Reported as Influential

    ERIC Educational Resources Information Center

    Tastan Kirik, Özgecan

    2013-01-01

    This study explores the science teaching efficacy beliefs of preservice elementary teachers and the relationship between efficacy beliefs and multiple factors such as antecedent factors (participation in extracurricular activities and number of science and science teaching methods courses taken), conceptual understanding, classroom management…

  17. E-Government and Citizen Adoption of Innovations: Factors Underlying Citizen Use of the Internet for State Tax Filing

    ERIC Educational Resources Information Center

    Boone, Michael A.

    2012-01-01

    Electronic government has been embraced by many organizations seeking to dramatically improve service delivery, but results to date have often fallen short of expectations. This dissertation is focused on state revenue agencies and their electronic tax filing mechanisms for state individual income taxes. It asks: What factors best explain whether…

  18. Governance factors in the identification of global conservation priorities for mammals.

    PubMed

    Eklund, Johanna; Arponen, Anni; Visconti, Piero; Cabeza, Mar

    2011-09-27

    Global conservation priorities have often been identified based on the combination of species richness and threat information. With the development of the field of systematic conservation planning, more attention has been given to conservation costs. This leads to prioritizing developing countries, where costs are generally low and biodiversity is high. But many of these countries have poor governance, which may result in ineffective conservation or in larger costs than initially expected. We explore how the consideration of governance affects the selection of global conservation priorities for the world's mammals in a complementarity-based conservation prioritization. We use data on Control of Corruption (Worldwide Governance Indicators project) as an indicator of governance effectiveness, and gross domestic product per capita as an indicator of cost. We show that, while core areas with high levels of endemism are always selected as important regardless of governance and cost values, there are clear regional differences in selected sites when biodiversity, cost or governance are taken into account separately. Overall, the analysis supports the concentration of conservation efforts in most of the regions generally considered of high priority, but stresses the need for different conservation approaches in different continents owing to spatial patterns of governance and economic development. PMID:21844045

  19. Governance factors in the identification of global conservation priorities for mammals.

    PubMed

    Eklund, Johanna; Arponen, Anni; Visconti, Piero; Cabeza, Mar

    2011-09-27

    Global conservation priorities have often been identified based on the combination of species richness and threat information. With the development of the field of systematic conservation planning, more attention has been given to conservation costs. This leads to prioritizing developing countries, where costs are generally low and biodiversity is high. But many of these countries have poor governance, which may result in ineffective conservation or in larger costs than initially expected. We explore how the consideration of governance affects the selection of global conservation priorities for the world's mammals in a complementarity-based conservation prioritization. We use data on Control of Corruption (Worldwide Governance Indicators project) as an indicator of governance effectiveness, and gross domestic product per capita as an indicator of cost. We show that, while core areas with high levels of endemism are always selected as important regardless of governance and cost values, there are clear regional differences in selected sites when biodiversity, cost or governance are taken into account separately. Overall, the analysis supports the concentration of conservation efforts in most of the regions generally considered of high priority, but stresses the need for different conservation approaches in different continents owing to spatial patterns of governance and economic development.

  20. Controlled Multiple Growth Factor Delivery from Bone Tissue Engineering Scaffolds via Designed Affinity

    PubMed Central

    Suárez-González, Darilis; Lee, Jae Sung; Diggs, Alisha; Lu, Yan; Nemke, Brett; Markel, Mark; Hollister, Scott J.

    2014-01-01

    It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release. We hypothesized that mineral coatings could be used as a platform for controlled incorporation and release of multiple growth factors. Specifically, mineral-coated scaffolds were “dip coated” in multiple growth factor solutions, and growth factor binding and release were dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate (β-TCP) scaffolds were fabricated using indirect solid-free form fabrication techniques and coated with a thin conformal mineral layer. Mineral-coated β-TCP scaffolds were sequentially dipped in recombinant human vascular endothelial growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral-binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for the incorporation of each growth factor. The dual release profile showed sustained release of both growth factors for over more than 60 days. Scaffolds releasing either rhVEGF alone or the combination of growth factors showed an increase in blood vessel ingrowth in a dose-dependent manner in a sheep intramuscular implantation model. This approach demonstrates a “modular design” approach, in which a controllable biologics carrier is integrated into a structural scaffold as a thin surface coating. PMID:24350567

  1. Multiple NUCLEAR FACTOR Y transcription factors respond to abiotic stress in Brassica napus L.

    PubMed

    Xu, Li; Lin, Zhongyuan; Tao, Qing; Liang, Mingxiang; Zhao, Gengmao; Yin, Xiangzhen; Fu, Ruixin

    2014-01-01

    Members of the plant NUCLEAR FACTOR Y (NF-Y) family are composed of the NF-YA, NF-YB, and NF-YC subunits. In Brassica napus (canola), each of these subunits forms a multimember subfamily. Plant NF-Ys were reported to be involved in several abiotic stresses. In this study, we demonstrated that multiple members of thirty three BnNF-Ys responded rapidly to salinity, drought, or ABA treatments. Transcripts of five BnNF-YAs, seven BnNF-YBs, and two BnNF-YCs were up-regulated by salinity stress, whereas the expression of thirteen BnNF-YAs, ten BnNF-YBs, and four BnNF-YCs were induced by drought stress. Under NaCl treatments, the expression of one BnNF-YA10 and four NF-YBs (BnNF-YB3, BnNF-YB7, BnNF-YB10, and BnNF-YB14) were greatly increased. Under PEG treatments, the expression levels of four NF-YAs (BnNF-YA9, BnNF-YA10, BnNF-YA11, and BnNF-YA12) and five NF-YBs (BnNF-YB1, BnNF-YB8, BnNF-YB10, BnNF-YB13, and BnNF-YB14) were greatly induced. The expression profiles of 20 of the 27 salinity- or drought-induced BnNF-Ys were also affected by ABA treatment. The expression levels of six NF-YAs (BnNF-YA1, BnNF-YA7, BnNF-YA8, BnNF-YA9, BnNF-YA10, and BnNF-YA12) and seven BnNF-YB members (BnNF-YB2, BnNF-YB3, BnNF-YB7, BnNF-YB10, BnNF-YB11, BnNF-YB13, and BnNF-YB14) and two NF-YC members (BnNF-YC2 and BnNF-YC3) were greatly up-regulated by ABA treatments. Only a few BnNF-Ys were inhibited by the above three treatments. Several NF-Y subfamily members exhibited collinear expression patterns. The promoters of all stress-responsive BnNF-Ys harbored at least two types of stress-related cis-elements, such as ABRE, DRE, MYB, or MYC. The cis-element organization of BnNF-Ys was similar to that of Arabidopsis thaliana, and the promoter regions exhibited higher levels of nucleotide sequence identity with Brassica rapa than with Brassica oleracea. This work represents an entry point for investigating the roles of canola NF-Y proteins during abiotic stress responses and provides insight into

  2. Multiple NUCLEAR FACTOR Y transcription factors respond to abiotic stress in Brassica napus L.

    PubMed

    Xu, Li; Lin, Zhongyuan; Tao, Qing; Liang, Mingxiang; Zhao, Gengmao; Yin, Xiangzhen; Fu, Ruixin

    2014-01-01

    Members of the plant NUCLEAR FACTOR Y (NF-Y) family are composed of the NF-YA, NF-YB, and NF-YC subunits. In Brassica napus (canola), each of these subunits forms a multimember subfamily. Plant NF-Ys were reported to be involved in several abiotic stresses. In this study, we demonstrated that multiple members of thirty three BnNF-Ys responded rapidly to salinity, drought, or ABA treatments. Transcripts of five BnNF-YAs, seven BnNF-YBs, and two BnNF-YCs were up-regulated by salinity stress, whereas the expression of thirteen BnNF-YAs, ten BnNF-YBs, and four BnNF-YCs were induced by drought stress. Under NaCl treatments, the expression of one BnNF-YA10 and four NF-YBs (BnNF-YB3, BnNF-YB7, BnNF-YB10, and BnNF-YB14) were greatly increased. Under PEG treatments, the expression levels of four NF-YAs (BnNF-YA9, BnNF-YA10, BnNF-YA11, and BnNF-YA12) and five NF-YBs (BnNF-YB1, BnNF-YB8, BnNF-YB10, BnNF-YB13, and BnNF-YB14) were greatly induced. The expression profiles of 20 of the 27 salinity- or drought-induced BnNF-Ys were also affected by ABA treatment. The expression levels of six NF-YAs (BnNF-YA1, BnNF-YA7, BnNF-YA8, BnNF-YA9, BnNF-YA10, and BnNF-YA12) and seven BnNF-YB members (BnNF-YB2, BnNF-YB3, BnNF-YB7, BnNF-YB10, BnNF-YB11, BnNF-YB13, and BnNF-YB14) and two NF-YC members (BnNF-YC2 and BnNF-YC3) were greatly up-regulated by ABA treatments. Only a few BnNF-Ys were inhibited by the above three treatments. Several NF-Y subfamily members exhibited collinear expression patterns. The promoters of all stress-responsive BnNF-Ys harbored at least two types of stress-related cis-elements, such as ABRE, DRE, MYB, or MYC. The cis-element organization of BnNF-Ys was similar to that of Arabidopsis thaliana, and the promoter regions exhibited higher levels of nucleotide sequence identity with Brassica rapa than with Brassica oleracea. This work represents an entry point for investigating the roles of canola NF-Y proteins during abiotic stress responses and provides insight into

  3. [A factor analysis method for contingency table data with unlimited multiple choice questions].

    PubMed

    Toyoda, Hideki; Haiden, Reina; Kubo, Saori; Ikehara, Kazuya; Isobe, Yurie

    2016-02-01

    The purpose of this study is to propose a method of factor analysis for analyzing contingency tables developed from the data of unlimited multiple-choice questions. This method assumes that the element of each cell of the contingency table has a binominal distribution and a factor analysis model is applied to the logit of the selection probability. Scree plot and WAIC are used to decide the number of factors, and the standardized residual, the standardized difference between the sample, and the proportion ratio, is used to select items. The proposed method was applied to real product impression research data on advertised chips and energy drinks. Since the results of the analysis showed that this method could be used in conjunction with conventional factor analysis model, and extracted factors were fully interpretable, and suggests the usefulness of the proposed method in the study of psychology using unlimited multiple-choice questions.

  4. [A factor analysis method for contingency table data with unlimited multiple choice questions].

    PubMed

    Toyoda, Hideki; Haiden, Reina; Kubo, Saori; Ikehara, Kazuya; Isobe, Yurie

    2016-02-01

    The purpose of this study is to propose a method of factor analysis for analyzing contingency tables developed from the data of unlimited multiple-choice questions. This method assumes that the element of each cell of the contingency table has a binominal distribution and a factor analysis model is applied to the logit of the selection probability. Scree plot and WAIC are used to decide the number of factors, and the standardized residual, the standardized difference between the sample, and the proportion ratio, is used to select items. The proposed method was applied to real product impression research data on advertised chips and energy drinks. Since the results of the analysis showed that this method could be used in conjunction with conventional factor analysis model, and extracted factors were fully interpretable, and suggests the usefulness of the proposed method in the study of psychology using unlimited multiple-choice questions. PMID:26964368

  5. Protective Factors Associated with Fewer Multiple Problem Behaviors Among Homeless/Runaway Youth

    PubMed Central

    Lightfoot, Marguerita; Stein, Judith A.; Tevendale, Heather; Preston, Kathleen

    2015-01-01

    Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth. PMID:22023279

  6. Are major behavioral and sociodemographic risk factors for mortality additive or multiplicative in their effects?

    PubMed

    Mehta, Neil; Preston, Samuel

    2016-04-01

    All individuals are subject to multiple risk factors for mortality. In this paper, we consider the nature of interactions between certain major sociodemographic and behavioral risk factors associated with all-cause mortality in the United States. We develop the formal logic pertaining to two forms of interaction between risk factors, additive and multiplicative relations. We then consider the general circumstances in which additive or multiplicative relations might be expected. We argue that expectations about interactions among socio-demographic variables, and their relation to behavioral variables, have been stated in terms of additivity. However, the statistical models typically used to estimate the relation between risk factors and mortality assume that risk factors act multiplicatively. We examine empirically the nature of interactions among five major risk factors associated with all-cause mortality: smoking, obesity, race, sex, and educational attainment. Data were drawn from the cross-sectional NHANES III (1988-1994) and NHANES 1999-2010 surveys, linked to death records through December 31, 2011. Our analytic sample comprised 35,604 respondents and 5369 deaths. We find that obesity is additive with each of the remaining four variables. We speculate that its additivity is a reflection of the fact that obese status is generally achieved later in life. For all pairings of socio-demographic variables, risks are multiplicative. For survival chances, it is much more dangerous to be poorly educated if you are black or if you are male. And it is much riskier to be a male if you are black. These traits, established at birth or during childhood, literally result in deadly combinations. We conclude that the identification of interactions among risk factors can cast valuable light on the nature of the process being studied. It also has public health implications by identifying especially vulnerable groups and by properly identifying the proportion of deaths

  7. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    SciTech Connect

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  8. The covariation of multiple risk factors in primary care: a latent class analysis.

    PubMed

    Funderburk, Jennifer S; Maisto, Stephen A; Sugarman, Dawn E; Wade, Mike

    2008-12-01

    There is a need to advance the quality of healthcare by increasing knowledge about multiple risk factors and how to intervene to improve health outcomes. In an effort to better describe the presentation of multiple risks, this study involved a database review to describe the prevalence and covariation of multiple risk factors in individuals presenting to primary care. Patients with a primary care encounter from January 1, 2005 to June 30, 2005 (N = 10,043) were identified from the Department of Veteran's Affair's medical database and information about the following risk factors was extracted: alcohol use, psychiatric distress, body mass, smoking status, blood pressure, and posttraumatic stress. Exploratory and confirmatory latent class analyses identified three classes of individuals. Class 1 consisted of individuals with an overall lower level of risk for health problems, but a moderately high likelihood of elevated blood pressure. Individuals in Class 2 appeared to have the greatest need for intervention because they had a moderate to high likelihood of reporting at risk alcohol use, smoking, depression, and posttraumatic stress. Class 3 consisted of individuals reporting the co-occurrence of at risk alcohol use, smoking, and elevated blood pressure. Similar to past research, the findings highlight the need for addressing multiple risk factors in primary care. In addition, this study expands on the literature by identifying specific patterns of covariation among different risk factors that suggest avenues for research and program development. PMID:18800242

  9. Neurotrophic factors and their effects in the treatment of multiple sclerosis

    PubMed Central

    Razavi, Shahnaz; Nazem, Ghasemi; Mardani, Mohammad; Esfandiari, Ebrahim; Salehi, Hossein; Esfahani, Sayyed Hamid Zarkesh

    2015-01-01

    Neurotrophins are small molecules of polypeptides, which include nerve growth factor (NGF) family, glial cell line–derived neurotrophic factor (GDNF) family ligands, and neuropoietic cytokines. These factors have an important role in neural regeneration, remyelination, and regulating the development of the peripheral and central nervous systems (PNS and CNS, respectively) by intracellular signaling through specific receptors. It has been suggested that the pathogenesis of human neurodegenerative disorders may be due to an alteration in the neurotrophic factors and their receptors. The use of neurotrophic factors as therapeutic agents is a novel strategy for restoring and maintaining neuronal function during neurodegenerative disorders such as multiple sclerosis. Innate and adaptive immune responses contribute to pathology of neurodegenerative disorders. Furthermore, autoimmune and mesenchymal stem cells, by the release of neurotrophic factors, have the ability to protect neuronal population and can efficiently suppress the formation of new lesions. So, these cells may be an alternative source for delivering neurotrophic factors into the CNS. PMID:25802822

  10. Socio-economic factors and immigrant population studies of multiple sclerosis.

    PubMed

    Berg-Hansen, P; Celius, E G

    2015-01-01

    The uneven geographical distribution of multiple sclerosis (MS) and the differences in disease severity observed between different ethnic groups indicate a complex interplay between genetic and environmental risk factors involved in the disease pathogenesis. Changes in MS risk after migration suggest influence of environmental factors on disease susceptibility. Whether the risk of MS is affected by socio-economic status (SES) is still controversial. In the present review, the combined knowledge from studies of migration and SES in MS is discussed.

  11. An Exploration of the Factors Influencing the Adoption of an IS Governance Framework

    ERIC Educational Resources Information Center

    Parker, Sharon L.

    2013-01-01

    This research explored IT governance framework adoption, leveraging established IS theories. It applied both the technology acceptance model (TAM) and the technology, organization, environment (TOE) models. The study consisted of developing a model utilizing TOE and TAM, deriving relevant hypotheses. Interviews with a group of practitioners…

  12. Government Style as a Factor in Information Flow: Television Programming in Argentina, l979-l988.

    ERIC Educational Resources Information Center

    John, Jeffrey Alan

    Noting that Argentina's recent history is particularly useful for analysis of the varying effects that differing government styles can have on a single mass communication system, a study compared Argentine (specifically Buenos Aires) television's 1979 programming schedule, prepared during a military dictatorship, with recent schedules prepared…

  13. Factor analysis and multiple regression between topography and precipitation on Jeju Island, Korea

    NASA Astrophysics Data System (ADS)

    Um, Myoung-Jin; Yun, Hyeseon; Jeong, Chang-Sam; Heo, Jun-Haeng

    2011-11-01

    SummaryIn this study, new factors that influence precipitation were extracted from geographic variables using factor analysis, which allow for an accurate estimation of orographic precipitation. Correlation analysis was also used to examine the relationship between nine topographic variables from digital elevation models (DEMs) and the precipitation in Jeju Island. In addition, a spatial analysis was performed in order to verify the validity of the regression model. From the results of the correlation analysis, it was found that all of the topographic variables had a positive correlation with the precipitation. The relations between the variables also changed in accordance with a change in the precipitation duration. However, upon examining the correlation matrix, no significant relationship between the latitude and the aspect was found. According to the factor analysis, eight topographic variables (latitude being the exception) were found to have a direct influence on the precipitation. Three factors were then extracted from the eight topographic variables. By directly comparing the multiple regression model with the factors (model 1) to the multiple regression model with the topographic variables (model 3), it was found that model 1 did not violate the limits of statistical significance and multicollinearity. As such, model 1 was considered to be appropriate for estimating the precipitation when taking into account the topography. In the study of model 1, the multiple regression model using factor analysis was found to be the best method for estimating the orographic precipitation on Jeju Island.

  14. Primary Factors Related to Multiple Placements for Children in Out-of-Home Care

    ERIC Educational Resources Information Center

    Eggertsen, Lars

    2008-01-01

    Using an ecological framework, this study identified which factors related to out-of-home placements significantly influenced multiple placements for children in Utah during 2000, 2001, and 2002. Multinomial logistic regression statistical procedures and a geographical information system (GIS) were used to analyze the data. The final model…

  15. The Effect of Auxiliary Variables and Multiple Imputation on Parameter Estimation in Confirmatory Factor Analysis

    ERIC Educational Resources Information Center

    Yoo, Jin Eun

    2009-01-01

    This Monte Carlo study investigates the beneficiary effect of including auxiliary variables during estimation of confirmatory factor analysis models with multiple imputation. Specifically, it examines the influence of sample size, missing rates, missingness mechanism combinations, missingness types (linear or convex), and the absence or presence…

  16. Effects of dietary factors on energy regulation: Consideration of multiple- versus single-dietary-factor models

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While short-term studies demonstrate consistent effects of dietary protein, fiber, glycemic index and energy density on energy intake, long-term effectiveness trials typically indicate small or non-significant effects of these dietary factors on long-term weight change. In consequence, most lifestyl...

  17. Service-Learning from a Distance: Partnering Multiple Universities and Local Governments in a Large Scale Initiative

    ERIC Educational Resources Information Center

    Poindexter, Sandra; Arnold, Pamela; Osterhout, Christopher

    2009-01-01

    Service-learning can be academically effective even when the distances between students and client organizations prevent face-to-face interchanges and site visits. Working with the State of Michigan and Michigan Townships Association, Michigan students from five universities learned about local government while helping Michigan townships develop…

  18. Multiple Motives, Conflicting Conceptions: Parsing the Contexts of Differentiated Access to Scientific Information in the Federal Government

    ERIC Educational Resources Information Center

    Oltmann, Shannon M.

    2012-01-01

    Scientific information, used by the U.S. federal government to formulate public policy in many arenas, is frequently contested and sometimes altered, blocked from publication, deleted from reports, or restricted in some way. This dissertation examines how and why restricted access to science policy (RASP) occurs through a comparative case study.…

  19. Factors Associated With Occupational Sun-Protection Policies in Local Government Organizations in Colorado

    PubMed Central

    Walkosz, Barbara J.; Buller, David B.; Andersen, Peter A.; Wallis, Allan; Buller, Mary Klein; Scott, Michael D.

    2015-01-01

    IMPORTANCE Skin cancer prevention remains a national priority. Reducing chronic UV radiation exposure for outdoor workers through sun-safety practices is an important step to help reduce the incidence of skin cancer. OBJECTIVE To determine the presence of occupational sun-safety policies at local government organizations in a single state. DESIGN, SETTING, AND PARTICIPANTS Of 571 potentially eligible local government organizations of Colorado cities, counties, and special tax districts, we enrolled 98 in a randomized pretest-posttest controlled experiment starting August 15, 2010, that evaluated an intervention to promote the adoption of sun-safety policies. We used a policy-coding protocol to evaluate personal sun-protection practices, environmental and administrative controls, and policy directives for sun safety starting February 10, 2011. We report the baseline assessment of the occupational sun-protection policies of these organizations. MAIN OUTCOMES AND MEASURES The presence of an occupational sun-safety policy. RESULTS Overall, 85 local government organizations (87%) had policies that required personal sun-protection practices, including the use of eyewear, hats, and protective clothing. However, of the 98 responding organizations, only 8 hat policies (8%), 10 eyewear policies (10%), and 7 clothing policies (7%) mentioned sun protection as the intent of the policy. Only cosmopoliteness, operationalized as proximity to an urban area, was associated with the presence of a sun-safety policy (odds ratio, 0.99 [95% CI, 0.98–1.00]; P = .02). CONCLUSIONS AND RELEVANCE Outdoor workers are at increased risk for skin cancer because of long-term exposure to solar UV radiation. Although organizational policies have the potential to increase sun protection in occupational settings, occupational sun-safety policies were uncommon among local governments. Opportunities exist for dermatologists and other physicians to influence occupational sun-safety practices and

  20. A Tri-Factor Model for Integrating Ratings Across Multiple Informants

    PubMed Central

    Bauer, Daniel J.; Howard, Andrea L.; Baldasaro, Ruth E.; Curran, Patrick J.; Hussong, Andrea M.; Chassin, Laurie; Zucker, Robert A.

    2014-01-01

    Psychologists often obtain ratings for target individuals from multiple informants such as parents or peers. In this paper we propose a tri-factor model for multiple informant data that separates target-level variability from informant-level variability and item-level variability. By leveraging item-level data, the tri-factor model allows for examination of a single trait rated on a single target. In contrast to many psychometric models developed for multitrait-multimethod data, the tri-factor model is predominantly a measurement model. It is used to evaluate item quality in scale development, test hypotheses about sources of target variability (e.g., sources of trait differences) versus informant variability (e.g., sources of rater bias), and generate integrative scores that are purged of the subjective biases of single informants. PMID:24079932

  1. Early B-cell Factor gene association with multiple sclerosis in the Spanish population

    PubMed Central

    Martínez, Alfonso; Mas, Ana; de las Heras, Virginia; Arroyo, Rafael; Fernández-Arquero, Miguel; de la Concha, Emilio G; Urcelay, Elena

    2005-01-01

    Background The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. Methods The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. Results Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). Conclusion Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them. PMID:16255771

  2. Multiple Mechanisms Are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells*

    PubMed Central

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle; Opresko, Lee K.; Coffey, Robert J.; Zangar, Richard; Wiley, H. Steven

    2008-01-01

    The number of distinct signaling pathways that can transactivate the epidermal growth factor receptor (EGFR) in a single cell type is unclear. Using a single strain of human mammary epithelial cells, we found that a wide variety of agonists, such as lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-α, require EGFR activity to induce ERK phosphorylation. In contrast, hepatocyte growth factor can stimulate ERK phosphorylation independent of the EGFR. EGFR transactivation also correlated with an increase in cell proliferation and could be inhibited with metalloprotease inhibitors. However, there were significant differences with respect to transactivation kinetics and sensitivity to different inhibitors. In particular, IGF-1 displayed relatively slow transactivation kinetics and was resistant to inhibition by the selective ADAM-17 inhibitor WAY-022 compared with LPA-induced transactivation. Studies using anti-ligand antibodies showed that IGF-1 transactivation required amphiregulin production, whereas LPA was dependent on multiple ligands. Direct measurement of ligand shedding confirmed that LPA treatment stimulated shedding of multiple EGFR ligands, but paradoxically, IGF-1 had little effect on the shedding rate of any ligand, including amphiregulin. Instead, IGF-1 appeared to work by enhancing EGFR activation of Ras in response to constitutively produced amphiregulin. This enhancement of EGFR signaling was independent of both receptor phosphorylation and PI-3-kinase activity, suggestive of a novel mechanism. Our studies demonstrate that within a single cell type, the EGFR autocrine system can couple multiple signaling pathways to ERK activation and that this modulation of EGFR autocrine signaling can be accomplished at multiple regulatory steps. PMID:18782770

  3. Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies.

    PubMed

    Xu, Wei; Boehm, Garth; Zheng, Qiang

    2016-01-01

    Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution.

  4. Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies

    PubMed Central

    Xu, Wei; Boehm, Garth; Zheng, Qiang

    2015-01-01

    Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution. PMID:26904402

  5. Defining high, medium and low impact prognostic factors for developing multiple sclerosis.

    PubMed

    Tintore, Mar; Rovira, Àlex; Río, Jordi; Otero-Romero, Susana; Arrambide, Georgina; Tur, Carmen; Comabella, Manuel; Nos, Carlos; Arévalo, María Jesús; Negrotto, Laura; Galán, Ingrid; Vidal-Jordana, Angela; Castilló, Joaquin; Palavra, Filipe; Simon, Eva; Mitjana, Raquel; Auger, Cristina; Sastre-Garriga, Jaume; Montalban, Xavier

    2015-07-01

    Natural history studies have identified factors that predict evolution to multiple sclerosis or risk of disability accumulation over time. Although these studies are based on large multicentre cohorts with long follow-ups, they have limitations such as lack of standardized protocols, a retrospective data collection or lack of a systematic magnetic resonance imaging acquisition and analysis protocol, often resulting in failure to take magnetic resonance and oligoclonal bands into account as joint covariates in the prediction models. To overcome some of these limitations, the aim of our study was to identify and stratify baseline demographic, clinical, radiological and biological characteristics that might predict multiple sclerosis development and disability accumulation using a multivariate approach based on a large prospective cohort of patients with clinically isolated syndromes. From 1995 to 2013, 1058 patients with clinically isolated syndromes were included. We evaluated the influence of baseline prognostic factors on the risk for developing clinically definite multiple sclerosis, McDonald multiple sclerosis, and disability accumulation (Expanded Disability Status Scale score of 3.0) based on univariate (hazard ratio with 95% confidence intervals) and multivariate (adjusted hazard ratio with 95% confidence intervals) Cox regression models. We ultimately included 1015 patients followed for a mean of 81 (standard deviation = 57) months. Female/male ratio was 2.1. Females exhibited a similar risk of conversion to multiple sclerosis and of disability accumulation compared to males. Each younger decade at onset was associated with a greater risk of conversion to multiple sclerosis and with a protective effect on disability. Patients with optic neuritis had a lower risk of clinically definite multiple sclerosis [hazard ratio 0.6 (0.5-0.8)] and disability progression [hazard ratio 0.5 (0.3-0.8)]; however, this protective effect remained marginal only for disability

  6. Genome-wide linkage analysis of multiple metabolic factors: evidence of genetic heterogeneity.

    PubMed

    Cheng, Ching-Yu; Lee, Kristine E; Duggal, Priya; Moore, Emily L; Wilson, Alexander F; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

    2010-01-01

    The metabolic syndrome is a highly complex disease and has become one of the major public-health challenges worldwide. We sought to identify genetic loci with potential influence on multiple metabolic factors in a white population in Beaver Dam, Wisconsin, and to explore the possibility of genetic heterogeneity by family history of diabetes (FHD). Three metabolic factors were generated using principal-component factor analysis, and they represented: (i) glycemia, (ii) blood pressure, and (iii) combined (BMI, high-density lipoprotein (HDL) cholesterol, and serum uric acid) factors. Multipoint model-free linkage analysis of these factors with 385 microsatellite markers was performed on 1,055 sib-pairs, using Haseman-Elston regression. Genome-wide suggestive evidence of linkage was found at 30 cM on chromosome 22q (empirical P (P(e)) = 0.0002) for the glycemia factor, at 188-191 cM on chromosome 1q (P(e) = 0.0007) for the blood pressure factor, and at 82 cM on chromosome 17q (P(e) = 0.0007) for the combined factor. Subset analyses of the families by FHD showed evidence of genetic heterogeneity, with divergent linkage signals in the subsets on at least four chromosomes. We found evidence of genetic heterogeneity by FHD for the three metabolic factors. The results also confirmed findings of previous studies that mapped components of the metabolic syndrome to a chromosome 1q region.

  7. Comparison of different multiple flow algorithms for topographic RUSLE factor (LS) calculation in Switzerland

    NASA Astrophysics Data System (ADS)

    Bircher, Pascal; Liniger, Hanspeter; Prasuhn, Volker

    2016-04-01

    Soil erosion is a well-known challenge both from a global perspective and in Switzerland, and it is assessed and discussed in many projects (e.g. national or European erosion risk maps). Meaningful assessment of soil erosion requires models that adequately reflect surface water flows. Various studies have attempted to achieve better modelling results by including multiple flow algorithms in the topographic length and slope factor (LS-factor) of the Revised Universal Soil Loss Equation (RUSLE). The choice of multiple flow algorithms is wide, and many of them have been implemented in programs or tools like Saga-Gis, GrassGis, ArcGIS, ArcView, Taudem, and others. This study compares six different multiple flow algorithms with the aim of identifying a suitable approach to calculating the LS factor for a new soil erosion risk map of Switzerland. The comparison of multiple flow algorithms is part of a broader project to model soil erosion for the entire agriculturally used area in Switzerland and to renew and optimize the current erosion risk map of Switzerland (ERM2). The ERM2 was calculated in 2009, using a high resolution digital elevation model (2 m) and a multiple flow algorithm in ArcView. This map has provided the basis for enforcing soil protection regulations since 2010 and has proved its worth in practice, but it has become outdated (new basic data are now available, e.g. data on land use change, a new rainfall erosivity map, a new digital elevation model, etc.) and is no longer user friendly (ArcView). In a first step towards its renewal, a new data set from the Swiss Federal Office of Topography (Swisstopo) was used to generate the agricultural area based on the existing field block map. A field block is an area consisting of farmland, pastures, and meadows which is bounded by hydrological borders such as streets, forests, villages, surface waters, etc. In our study, we compared the six multiple flow algorithms with the LS factor calculation approach used in

  8. Race/Ethnicity and Multiple Cancer Risk Factors among Individuals Seeking Smoking Cessation Treatment

    PubMed Central

    Kendzor, Darla E.; Costello, Tracy J.; Li, Yisheng; Vidrine, Jennifer Irvin; Mazas, Carlos A.; Reitzel, Lorraine R.; Cinciripini, Paul M.; Cofta-Woerpel, Ludmila M.; Businelle, Michael S.; Wetter, David W.

    2016-01-01

    Smoking in combination with other behavioral risk factors is known to have a negative influence on health, and individuals who smoke typically engage in multiple risk behaviors. However, little is known about the clustering of risk behaviors among smokers of varying race/ethnicity. The purpose of this study was to examine patterns of cancer risk behaviors and to identify predictors of multiple risk behaviors in a racially/ethnically diverse sample of individuals seeking smoking cessation treatment. Overweight/obesity, at-risk alcohol consumption, and insufficient physical activity were measured in 424 smokers (African American, n = 144; Latino, n = 141; Caucasian, n = 139). Results indicated that 90% of participants reported behavioral cancer risk factors in addition to smoking. Approximately 70% of participants were overweight or obese, 48% engaged in at-risk drinking, and 27% were insufficiently physically active. Univariate analyses indicated that race/ethnicity, p < .001, smoking level, p = .03, and marital status, p = .04, were significant predictors of multiple risk behaviors, although only race/ethnicity remained a significant predictor, p < .001, when gender, smoking level, age, education, household income, marital status, and health insurance status were included in a multivariate model. Multivariate analysis indicated that the odds of engaging in multiple risk behaviors were significantly higher among Latinos, OR = 2.85, and African Americans, OR = 1.86, than Caucasians. Our findings highlight the need for research aimed at identifiying determinants of racial/ethnic differences in multiple risk behaviors, and indicate the importance of developing culturally sensitive interventions that target multiple risk behaviors. PMID:18990734

  9. The Causal Factors Associated with the Loving Care of the Mothers of Children with Multiple Disabilities

    PubMed Central

    Sadati, Ahmad Kalateh; Salehzade, Hamze; Hemmati, Soroor; Darvish, Manijeh; Heydari, Seyed Taghi; Tabrizi, Reza

    2015-01-01

    Background: Families with disabled children need more psycho-social considerations. Motherhood care of the children with multiple disabilities is difficult. Due to its importance, the aim of this study was to investigate the causal factors affecting loving care of mothers of children with multiple disabilities. Methods: The study used a cross-sectional method in which 75 mothers of exceptional children with multiple disabilities (physical and mental) in elementary schools in Shiraz, Iran. The data were collected through questionnaires which, besides demographical factors, evaluated the relationship between mothers’ loving care of children with multiple disabilities and four other variables including purpose in life, life satisfaction, religious attitude, and sense of coherence. Mann-Whitney U was used for comparison between mothers’ loving care and other variables. Results: Results revealed that demographic variables did not have a significant relationship with loving care. In the case of social variables, there was a significant relationship between mothers’ loving care and purpose in life (P<0.001), religious attitude (P<0.001), and life satisfaction (P=0.01). Conclusion: Motherhood care of disabled children is a unique phenomenon which is due to attachment of mother-child situation. Nevertheless, these mothers are vulnerable and marginalized people who need more attention and social supports provided by related governmental institutions and also NGOs actors. PMID:26448958

  10. Description and evaluation of the smoking cessation component of a multiple risk factor intervention program.

    PubMed

    Malotte, C K; Fielding, J E; Danaher, B G

    1981-08-01

    The smoking cessation component of a residential program which attempts to concurrently intervene on several risk factors related to chronic disease is described. Seventy-two per cent of the 43 smokers in the first 13 cohorts were abstinent at discharge. Fifty-five per cent were abstinent at two months. Six-month data for the first nine cohorts show 53 per cent abstinence. Possible advantages and disadvantages of a multiple behavior change program in a residential setting are discussed. PMID:7258447

  11. Association of Multiple Behavioral Risk Factors with Adolescents’ Willingness to Engage in eHealth Promotion

    PubMed Central

    Abraham, Anisha A.; Graham, Amanda L.; Wilson, Lara D.; Walker, Leslie R.

    2009-01-01

    Objective This study examines adolescents’ willingness to use the internet and other forms of technology for health promotion purposes (i.e., “eHealth promotion” willingness) and determines if a relationship exists between adolescents’ behavioral risks and their eHealth promotion willingness. Methods A total of 332 adolescents provided data at a routine medical check-up, including assessments of technology access, eHealth promotion willingness, and multiple behavioral risk factors for child- and adult-onset disease (body mass index, physical activity, smoking, sun protection, depression). Results The level of access to technology among the sample was high, with moderate willingness to engage in eHealth promotion. After adjusting for adolescents’ access to technology, the presence of multiple behavioral risk factors was positively associated with willingness to use technology for health promotion purposes (β =.12, p =.03). Conclusions Adolescents with both single and multiple behavioral risk factors are in need of health promotion to prevent the onset of disease later in life. eHealth appears to be an acceptable and promising intervention approach with this population. PMID:18723566

  12. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel.

    PubMed

    Bruggeman, Kiara F; Rodriguez, Alexandra L; Parish, Clare L; Williams, Richard J; Nisbet, David R

    2016-09-23

    Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine. PMID:27517970

  13. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

    NASA Astrophysics Data System (ADS)

    Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

    2016-09-01

    Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

  14. To Fish or Not to Fish: Factors at Multiple Scales Affecting Artisanal Fishers' Readiness to Exit a Declining Fishery

    PubMed Central

    Daw, Tim M.; Cinner, Joshua E.; McClanahan, Timothy R.; Brown, Katrina; Stead, Selina M.; Graham, Nicholas A. J.; Maina, Joseph

    2012-01-01

    Globally, fisheries are challenged by the combined impacts of overfishing, degradation of ecosystems and impacts of climate change, while fisheries livelihoods are further pressured by conservation policy imperatives. Fishers' adaptive responses to these pressures, such as exiting from a fishery to pursue alternative livelihoods, determine their own vulnerability, as well as the potential for reducing fishing effort and sustaining fisheries. The willingness and ability to make particular adaptations in response to change, such as exiting from a declining fishery, is influenced by economic, cultural and institutional factors operating at scales from individual fishers to national economies. Previous studies of exit from fisheries at single or few sites, offer limited insight into the relative importance of individual and larger-scale social and economic factors. We asked 599 fishers how they would respond to hypothetical scenarios of catch declines in 28 sites in five western Indian Ocean countries. We investigated how socioeconomic variables at the individual-, household- and site-scale affected whether they would exit fisheries. Site-level factors had the greatest influence on readiness to exit, but these relationships were contrary to common predictions. Specifically, higher levels of infrastructure development and economic vitality - expected to promote exit from fisheries - were associated with less readiness to exit. This may be due to site level histories of exit from fisheries, greater specialisation of fishing households, or higher rewards from fishing in more economically developed sites due to technology, market access, catch value and government subsidies. At the individual and household scale, fishers from households with more livelihood activities, and fishers with lower catch value were more willing to exit. These results demonstrate empirically how adaptive responses to change are influenced by factors at multiple scales, and highlight the importance

  15. To fish or not to fish: factors at multiple scales affecting artisanal fishers' readiness to exit a declining fishery.

    PubMed

    Daw, Tim M; Cinner, Joshua E; McClanahan, Timothy R; Brown, Katrina; Stead, Selina M; Graham, Nicholas A J; Maina, Joseph

    2012-01-01

    Globally, fisheries are challenged by the combined impacts of overfishing, degradation of ecosystems and impacts of climate change, while fisheries livelihoods are further pressured by conservation policy imperatives. Fishers' adaptive responses to these pressures, such as exiting from a fishery to pursue alternative livelihoods, determine their own vulnerability, as well as the potential for reducing fishing effort and sustaining fisheries. The willingness and ability to make particular adaptations in response to change, such as exiting from a declining fishery, is influenced by economic, cultural and institutional factors operating at scales from individual fishers to national economies. Previous studies of exit from fisheries at single or few sites, offer limited insight into the relative importance of individual and larger-scale social and economic factors. We asked 599 fishers how they would respond to hypothetical scenarios of catch declines in 28 sites in five western Indian Ocean countries. We investigated how socioeconomic variables at the individual-, household- and site-scale affected whether they would exit fisheries. Site-level factors had the greatest influence on readiness to exit, but these relationships were contrary to common predictions. Specifically, higher levels of infrastructure development and economic vitality - expected to promote exit from fisheries - were associated with less readiness to exit. This may be due to site level histories of exit from fisheries, greater specialisation of fishing households, or higher rewards from fishing in more economically developed sites due to technology, market access, catch value and government subsidies. At the individual and household scale, fishers from households with more livelihood activities, and fishers with lower catch value were more willing to exit. These results demonstrate empirically how adaptive responses to change are influenced by factors at multiple scales, and highlight the importance

  16. Outrage Factors in Government Press Releases of Food Risk and Their Influence on News Media Coverage.

    PubMed

    Ju, Youngkee; Lim, Jeongsub; Shim, Minsun; You, Myoungsoon

    2015-08-01

    An appropriate level of risk perception should be a critical issue in modern "risk society." There have been many studies on the influences on risk perception. This study investigates whether risk communication scholar Dr. Peter Sandman's outrage factors intensify journalistic attention to health risks from food consumption. A content analysis of a health institution's press releases was conducted to examine 15 outrage factors of food risks conveyed in the governmental risk communication. In addition, the news stories covering the food risks informed by the press releases were calculated to evaluate the relation between outrage factors of a risk and the number of news stories covering the risk. Results showed that controllability was the most salient outrage factor, followed by trust, voluntariness, familiarity, and human origin; the greater the outrage score of a risk, the more news stories of the risk. For individual outrage factors, a risk with an implication of catastrophic potential was associated with an increase of news stories. Food providers' distrustful behaviors also influenced journalistic attention to the food risks. The implication of the findings to health message designers is discussed.

  17. Outrage Factors in Government Press Releases of Food Risk and Their Influence on News Media Coverage.

    PubMed

    Ju, Youngkee; Lim, Jeongsub; Shim, Minsun; You, Myoungsoon

    2015-08-01

    An appropriate level of risk perception should be a critical issue in modern "risk society." There have been many studies on the influences on risk perception. This study investigates whether risk communication scholar Dr. Peter Sandman's outrage factors intensify journalistic attention to health risks from food consumption. A content analysis of a health institution's press releases was conducted to examine 15 outrage factors of food risks conveyed in the governmental risk communication. In addition, the news stories covering the food risks informed by the press releases were calculated to evaluate the relation between outrage factors of a risk and the number of news stories covering the risk. Results showed that controllability was the most salient outrage factor, followed by trust, voluntariness, familiarity, and human origin; the greater the outrage score of a risk, the more news stories of the risk. For individual outrage factors, a risk with an implication of catastrophic potential was associated with an increase of news stories. Food providers' distrustful behaviors also influenced journalistic attention to the food risks. The implication of the findings to health message designers is discussed. PMID:26065830

  18. Orthogonal matrix factorization enables integrative analysis of multiple RNA binding proteins

    PubMed Central

    Stražar, Martin; Žitnik, Marinka; Zupan, Blaž; Ule, Jernej; Curk, Tomaž

    2016-01-01

    Motivation: RNA binding proteins (RBPs) play important roles in post-transcriptional control of gene expression, including splicing, transport, polyadenylation and RNA stability. To model protein–RNA interactions by considering all available sources of information, it is necessary to integrate the rapidly growing RBP experimental data with the latest genome annotation, gene function, RNA sequence and structure. Such integration is possible by matrix factorization, where current approaches have an undesired tendency to identify only a small number of the strongest patterns with overlapping features. Because protein–RNA interactions are orchestrated by multiple factors, methods that identify discriminative patterns of varying strengths are needed. Results: We have developed an integrative orthogonality-regularized nonnegative matrix factorization (iONMF) to integrate multiple data sources and discover non-overlapping, class-specific RNA binding patterns of varying strengths. The orthogonality constraint halves the effective size of the factor model and outperforms other NMF models in predicting RBP interaction sites on RNA. We have integrated the largest data compendium to date, which includes 31 CLIP experiments on 19 RBPs involved in splicing (such as hnRNPs, U2AF2, ELAVL1, TDP-43 and FUS) and processing of 3’UTR (Ago, IGF2BP). We show that the integration of multiple data sources improves the predictive accuracy of retrieval of RNA binding sites. In our study the key predictive factors of protein–RNA interactions were the position of RNA structure and sequence motifs, RBP co-binding and gene region type. We report on a number of protein-specific patterns, many of which are consistent with experimentally determined properties of RBPs. Availability and implementation: The iONMF implementation and example datasets are available at https://github.com/mstrazar/ionmf. Contact: tomaz.curk@fri.uni-lj.si Supplementary information: Supplementary data are available

  19. Study of Core Competency Elements and Factors Affecting Performance Efficiency of Government Teachers in Northeastern Thailand

    ERIC Educational Resources Information Center

    Chansirisira, Pacharawit

    2012-01-01

    The research aimed to investigate the core competency elements and the factors affecting the performance efficiency of the civil service teachers in the northeastern region, Thailand. The research procedure consisted of two steps. In the first step, the data were collected using a questionnaire with the reliability (Cronbach's Alpha) of 0.90. The…

  20. The association of reproductive and lifestyle factors with a score of multiple endogenous hormones

    PubMed Central

    Shafrir, Amy L.; Zhang, Xuehong; Poole, Elizabeth M.; Hankinson, Susan E.; Tworoger, Shelley S.

    2014-01-01

    Introduction We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. Methods This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. Results The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation=2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p<0.0001) and each 15 grams/day increase in alcohol consumption was associated with a 0.41 (95%CI: 0.18, 0.63) unit increase in the score (p=0.0004). Family history of breast cancer, age at menarche, and physical activity were not associated with the score. Conclusions Reproductive breast cancer risk factors were not associated with elevated levels of multiple endogenous hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones. PMID:25048255

  1. An Evaluation of Multiple Behavioral Risk Factors for Cancer in a Working Class, Multi-Ethnic Population

    PubMed Central

    Goodman, Melody S.; Li, Yi; Bennett, Gary G.; Stoddard, Anne M.; Emmons, Karen M.

    2012-01-01

    Behavioral risk factors for cancer tend to cluster within individuals, which can compound risk beyond that associated with the individual risk factors alone. There has been increasing attention paid to the prevalence of multiple risk factors (MRF) for cancer, and to the importance of designing interventions that help individuals reduce their risks across multiple behaviors simultaneously. The purpose of this paper is to develop methodology to identify an optimal linear combination of multiple risk factors (score function) which would facilitate evaluation of cancer interventions. PMID:23227033

  2. High-power optical millimeter-wave signal generation with tunable frequency multiplication factor

    NASA Astrophysics Data System (ADS)

    Han, Yi-shi; Zheng, Zhenyu; Luo, Zhixiao; Min, Zhixuan; Xu, Ou; Liu, Jie

    2015-01-01

    This work demonstrates a simple and novel scheme for millimeter-wave (MMW) signal generation using optical multi-sidebands (OMSB) modulation. In the proposed methods, several pairs of optical sidebands can be generated by employing parallel phase modulators driven by a low frequency radio frequency (RF) signal. The optical sidebands will beat at a photodetector (PD) to generate high frequency MMW signal with tunable frequency multiplication factor, such as frequency octupling, 12-tupling, 16-tupling and 18-tupling. Since no optical filters or DC bias are used, the MMW signal has the evident character of high-power output. A generalized analytic expression and simulation verification for generating the frequency multi-tupling MMW signal are developed. The influences caused by non-ideal factors are discussed in detail, and undesired power ratios versus non-ideal factors are plotted and analyzed.

  3. Fuzzy based power factor improvement strategy for a multiple connected AC-DC converter fed drive

    NASA Astrophysics Data System (ADS)

    Radhakrishnan, N.; Muthiah, Ramaswamy

    2012-01-01

    The main focus of this paper is to design a Fuzzy based control algorithm to realize an improvement in the input power factor of a multiple connected AC-DC converter fed drive system. It incorporates the role of fuzzy inference principles to generate appropriate PWM pulses for the power switches at the second stage of the power module. The philosophy is developed, with a view to reshape the input current phasor and enables it to align with the supply voltage wave in the perspective of improving the input power factor. The closed loop scheme evaluated using MATLAB based simulation exhibits an enhancement in supply power factor over a range of operating loads in addition to illustrating the speed regulating capability of the drive.

  4. Robustness of the fractal regime for the multiple-scattering structure factor

    NASA Astrophysics Data System (ADS)

    Katyal, Nisha; Botet, Robert; Puri, Sanjay

    2016-08-01

    In the single-scattering theory of electromagnetic radiation, the fractal regime is a definite range in the photon momentum-transfer q, which is characterized by the scaling-law behavior of the structure factor: S(q) ∝ 1 /q df. This allows a straightforward estimation of the fractal dimension df of aggregates in Small-Angle X-ray Scattering (SAXS) experiments. However, this behavior is not commonly studied in optical scattering experiments because of the lack of information on its domain of validity. In the present work, we propose a definition of the multiple-scattering structure factor, which naturally generalizes the single-scattering function S(q). We show that the mean-field theory of electromagnetic scattering provides an explicit condition to interpret the significance of multiple scattering. In this paper, we investigate and discuss electromagnetic scattering by three classes of fractal aggregates. The results obtained from the TMatrix method show that the fractal scaling range is divided into two domains: (1) a genuine fractal regime, which is robust; (2) a possible anomalous scaling regime, S(q) ∝ 1 /qδ, with exponent δ independent of df, and related to the way the scattering mechanism uses the local morphology of the scatterer. The recognition, and an analysis, of the latter domain is of importance because it may result in significant reduction of the fractal regime, and brings into question the proper mechanism in the build-up of multiple-scattering.

  5. Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities

    PubMed Central

    Dai, Chao; Li, Wenyuan; Tjong, Harianto; Hao, Shengli; Zhou, Yonggang; Li, Qingjiao; Chen, Lin; Zhu, Bing; Alber, Frank; Jasmine Zhou, Xianghong

    2016-01-01

    Three-dimensional (3D) genome structures vary from cell to cell even in an isogenic sample. Unlike protein structures, genome structures are highly plastic, posing a significant challenge for structure-function mapping. Here we report an approach to comprehensively identify 3D chromatin clusters that each occurs frequently across a population of genome structures, either deconvoluted from ensemble-averaged Hi-C data or from a collection of single-cell Hi-C data. Applying our method to a population of genome structures (at the macrodomain resolution) of lymphoblastoid cells, we identify an atlas of stable inter-chromosomal chromatin clusters. A large number of these clusters are enriched in binding of specific regulatory factors and are therefore defined as ‘Regulatory Communities.' We reveal two major factors, centromere clustering and transcription factor binding, which significantly stabilize such communities. Finally, we show that the regulatory communities differ substantially from cell to cell, indicating that expression variability could be impacted by genome structures. PMID:27240697

  6. Factors Governing Stemflow Production from Plantation Grown Teak Trees in Thailand

    NASA Astrophysics Data System (ADS)

    Tanaka, N.; Levia, D. F., Jr.; Igarashi, Y.; Yoshifuji, N.; Tanaka, K.; Chatchai, T.; Nanko, K.; Suzuki, M.; Kumagai, T.

    2015-12-01

    Stemflow (SF) is recognized as an important process delivering water, solute, and particulate fluxes to spatially localized areas of the forest floor. Using both long-term SF data from nine even-aged deciduous teak trees grown in the same plantation and meteorological data from a nearby tower, this study seeks to better understand how: (1) specific biotic and abiotic factors control stand-scale SF production of teak; and (2) various biotic and abiotic factors affect tree-to-tree variations in teak SF production. A conventional regression analysis of SF volume against rainfall indicates that, for five individuals among the nine, SF was more efficiently produced in the leafless than in the leafed. However, for the other individuals, there was no such a relation, suggesting tree-to-tree variation in the response of SF to canopy status. A boosted regression tree (BRT) analysis setting daily basis SF funneling ratios (SFF) of the nine trees as dependent variables, indicates that SFF was intricately controlled by a variety of biotic and abiotic factors. The top six influential factors were, in descending order, rainfall duration, tree height, rainfall intensity, air temperature, wind speed, and antecedent dry period length having positive, negative, positive, negative, positive, and negative influence on SFF, respectively. Although teak exhibits drastic intra-annual changes in leaf phenology, leaf area index (LAI) had an unexpectedly small influence on SFF on a stand scale. Additional BRT analyses focusing on individuals with the maximum and the minimum SFF values (among the nine individuals) showed that there was considerable tree-to-tree variation in an array of the influential variables for SFF, even though they were planted in the same year and grown in the same plot. In addition to this difference, the BRT analyses also showed that response of SFF to LAI differs between the two individuals. The differentiating responses to LAI depending on individuals may be the

  7. Multiple risk factor interventions for primary prevention of coronary heart disease

    PubMed Central

    Ebrahim, Shah; Beswick, Andrew; Burke, Margaret; Smith, George Davey

    2014-01-01

    Background Primary prevention programmes in many countries attempt to reduce mortality and morbidity due to coronary heart disease (CHD) through risk factor modification. It is widely believed that multiple risk factor intervention using counselling and educational methods is efficacious and cost-effective and should be expanded. Recent trials examining risk factor changes have cast considerable doubt on the effectiveness of these multiple risk factor interventions. Objectives To assess the effects of multiple risk factor intervention for reducing cardiovascular risk factors, total mortality, and mortality from CHD among adults without clinical evidence of established cardiovascular disease. Search strategy MEDLINE was searched for the original review to 1995. This was updated by searching the Cochrane Central Register of Controlled Trials on The Cochrane Library Issue 3 2001, MEDLINE(2000 to September 2001) and EMBASE (1998 to September 2001). Selection criteria Intervention studies using counselling or education to modify more than one cardiovascular risk factor in adults from general populations, occupational groups, or high risk groups. Trials of less than 6 months duration were excluded. Data collection and analysis Data were extracted by two reviewers independently. Investigators were contacted to obtain missing information. Main results A total of 39 trials were found of which ten reported clinical event data. In the ten trials with clinical event end-points, the pooled odds ratios for total and CHD mortality were 0.96 (95% confidence intervals (CI) 0.92 to 1.01) and 0.96 (95% CI 0.89 to 1.04) respectively. Net changes in systolic and diastolic blood pressure, and blood cholesterol were (weighted mean differences) −3.6 mmHg (95% CI −3.9 to −3.3 mmHg), −2.8 mmHg (95% CI −2.9 to −2.6 mmHg) and −0.07 mMol/l (95% CI −0.8 to −0.06 mMol/l) respectively. Odds of reduction in smoking prevalence was 20% (95% CI 8% to 31%). Statistical heterogeneity

  8. Multiple Signaling Pathways Converge on the Cbfa1/Runx2 Transcription Factor to Regulate Osteoblast Differentiation

    PubMed Central

    Franceschi, Renny T.; Xiao, Guozhi; Jiang, Di; Gopalakrishnan, Rajaram; Yang, Shuying; Reith, Elizabeth

    2013-01-01

    The Cbfa1/Runx2 transcription factor is essential for osteoblast differentiation. However, levels of Runx2 are often not well correlated with its transcriptional activity suggesting that this factor must be activated either by covalent modification or through interactions with other nuclear components. Runx2 is phosphorylated and activated by the mitogen-activated protein kinase (MAPK) pathway. This pathway is stimulated in at least two ways: by binding of type I collagen to β2β1 integrins on the osteoblast surface and by treatment of cells with the osteogenic growth factor, FGF2. Protein kinase A (PKA) also may phosphorylate/activate Runx2 under certain conditions. Runx2 activity also is enhanced by factors known to stimulate specific signal transduction pathways such as PTH/PTHrP (signals through PKA and PKC pathways) and BMPs (Signal through Smad proteins). Interactions with Runx2 are complex involving both binding of distinct components such as AP-1 factors and Smads to separate sites on DNA, direct interactions between Runx2 and AP-1/Smad factors and MAPK or PKA-dependent Runx2 phosphorylation. These findings suggest that Runx2 plays a central role in coordinating multiple signals involved in osteoblast differentiation. PMID:12952183

  9. Reported Pain During Labour – A Qualitative Study of Influencing Factors among Parturient During Confinement in Private or Government Hospital

    PubMed Central

    Ravishankar, M.; Hemanthkumar, V.R.

    2016-01-01

    Introduction Labour pain is distressing and it produces undue side effects both to the mother and the baby. The incidence is high in developing countries like India where the awareness about labour analgesia is still lacking. Aim It is to find out the incidence of labour pain and the influence of various described factors on pain with a comparison between patients admitted in a government set up with a private set up in a south Indian semi-urban area. Materials and Methods Two hundred continuous uneventful normal deliveries each in a Government (group G) and a private hospital (group P) were enrolled for the study. The reported pain during labour was noted 6-7 hours after delivery by interacting with the patient. The factors like age of the mother, sex and weight of the baby, literacy, socioeconomic status, the use of oxytocics and analgesia were evaluated. Results The incidence of severe pain was more in group G (43.5%) than group P (12%). There was no analgesic intervention in 68.5% in group G while it was 13.5% (27/200) in group P. Even among these 27 patients who did not receive analgesics, only three parturients reported severe pain. Even administration of analgesics in a Government set up did not decrease pain to a significant extent. There were richer and more literate patients in group P. Booked cases were less in group G. Logistic regression analyses to find out factors which influenced pain in either group was used. Gravida, analgesic intervention and admission in a Govt. hospital influenced the pain experience of the parturient. There was minimal antenatal preparation in both the groups. There were no post partum complications. Conclusion Mothers suffered from labour pain to a significant extent and there is an urgent need for awareness about labour analgesia. Primigravida, admission in a Govt. set up and analgesic interventions were the factors which influenced pain than others. Patients admitted in Govt. hospitals suffered more pain with less analgesic

  10. Group-fitted ab initiosingle- and multiple-scattering EXAFS Debye-Waller factors

    NASA Astrophysics Data System (ADS)

    Dimakis, Nicholas; Bunker, Grant

    2002-05-01

    X-ray absorption fine structure (XAFS) spectroscopy is one of the few direct probes of the structure of metalloprotein binding that is equally applicable to proteins in crystals, solutions, and membranes. Despite considerable progress in the calculation of the photoelectron scattering aspects of XAFS, calculation of the vibrational aspects has lagged because of the difficulty of the calculations. We report here initial results that express single- and multiple-scattering Debye-Waller factors as polynomial functions of first shell radial distance for metal-peptide complexes, enabling quantitatively accurate full multiple-scattering XAFS data analysis of active sites of unknown structure at arbitrary temperatures without the use of ad hoc assumptions.

  11. Patterns and correlates of multiple risk factors for adult-onset cancer among adolescents

    PubMed Central

    MAYS, DARREN; PESHKIN, BETH N.; WALKER, LESLIE R.; ABRAHAM, ANISHA A.; HAWKINS, KIRSTEN B.; TERCYAK, KENNETH P.

    2012-01-01

    We investigated patterns and correlates of multiple, adult-onset cancer risk factors (MCRFs) among adolescents. Baseline data from an intervention efficacy trial were analyzed to examine patterns of co-occurring MCRFs and sociodemographic and theoretical (e.g., prevention self-efficacy) correlates of MCRFs among adolescents (N = 50) age 13 – 21. The mean total MCRFs was 4.6 (SD = 1.6; range 0–9). The most common risk factors were intentions to use alcohol (n = 40, 80%), < 5 daily servings of fruits/vegetables (n = 40, 80%), and lifetime alcohol use (n = 38, 76%). MCRFs commonly co-occurred, suggesting a clustered risk profile. Greater age (B = 0.19 95% CI 0.01, 0.38) and lower prevention self-efficacy (B = −0.16, 95% CI −0.02, −0.30) were significantly (p < 0.05) associated with MCRFs. Multiple health behavior change interventions are needed to prevent accumulation of risk factors as youth mature. Self-efficacy may be an important target for prevention interventions. PMID:22363044

  12. Science Teaching Efficacy of Preservice Elementary Teachers: Examination of the Multiple Factors Reported as Influential

    NASA Astrophysics Data System (ADS)

    Taştan Kırık, Özgecan

    2013-12-01

    This study explores the science teaching efficacy beliefs of pr-service elementary teachers and the relationship between efficacy beliefs and multiple factors such as antecedent factors (participation in extracurricular activities and number of science and science teaching methods courses taken), conceptual understanding, classroom management beliefs and science teaching attitudes. Science education majors ( n = 71) and elementary education majors ( n = 262) were compared with respect to these variables. Finally, the predictors of two constructs of science teaching efficacy beliefs, personal science teaching efficacy (PSTE) and science teaching outcome expectancy (STOE), were examined by multiple linear regression analysis. According to the results, participation in extracurricular activities has a significant but low correlation with science concept knowledge, science teaching attitudes, PSTE and STOE. In addition, there is a small but significant correlation between science concept knowledge and outcome expectancy, which leads the idea that preservice elementary teachers' conceptual understanding in science contributes to their science teaching self-efficacy. This study reveals a moderate correlation between science teaching attitudes and STOE and a high correlation between science teaching attitudes and PSTE. Additionally, although the correlation coefficient is low, the number of methodology courses was found to be one of the correlates of science teaching attitudes. Furthermore, students of both majors generally had positive self-efficacy beliefs on both the STOE and PSTE. Specifically, science education majors had higher science teaching self-efficacy than elementary education majors. Regression results showed that science teaching attitude is the major factor in predicting both PSTE and STOE for both groups.

  13. FF domains of CA150 bind transcription and splicing factors through multiple weak interactions.

    PubMed

    Smith, Matthew J; Kulkarni, Sarang; Pawson, Tony

    2004-11-01

    The human transcription factor CA150 modulates human immunodeficiency virus type 1 gene transcription and contains numerous signaling elements, including six FF domains. Repeated FF domains are present in several transcription and splicing factors and can recognize phosphoserine motifs in the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Using mass spectrometry, we identify a number of nuclear binding partners for the CA150 FF domains and demonstrate a direct interaction between CA150 and Tat-SF1, a protein involved in the coupling of splicing and transcription. CA150 FF domains recognize multiple sites within the Tat-SF1 protein conforming to the consensus motif (D/E)(2/5)-F/W/Y-(D/E)(2/5). Individual FF domains are capable of interacting with Tat-SF1 peptide ligands in an equivalent and noncooperative manner, with affinities ranging from 150 to 500 microM. Repeated FF domains therefore appear to bind their targets through multiple weak interactions with motifs comprised of negatively charged residues flanking aromatic amino acids. The RNAPII CTD represents a consensus FF domain-binding site, contingent on generation of the requisite negative charges by phosphorylation of serines 2 and 5. We propose that CA150, through the dual recognition of acidic motifs in proteins such as Tat-SF1 and the phosphorylated CTD, could mediate the recruitment of transcription and splicing factors to actively transcribing RNAPII.

  14. Several developmental and morphogenetic factors govern the evolution of stomatal patterning in land plants.

    PubMed

    Rudall, Paula J; Hilton, Jason; Bateman, Richard M

    2013-11-01

    We evaluate stomatal development in terms of its primary morphogenetic factors and place it in a phylogenetic context, including clarification of the contrasting specialist terms that are used by different sets of researchers. The genetic and structural bases for stomatal development are well conserved and increasingly well understood in extant taxa, but many phylogenetically crucial plant lineages are known only from fossils, in which it is problematic to infer development. For example, specialized lateral subsidiary cells that occur adjacent to the guard cells in some taxa can be derived either from the same cell lineage as the guard cells or from an adjacent cell file. A potentially key factor in land-plant evolution is the presence (mesogenous type) or absence (perigenous type) of at least one asymmetric division in the cell lineage leading to the guard-mother cell. However, the question whether perigenous or mesogenous development is ancestral in land plants cannot yet be answered definitively based on existing data. Establishment of 'fossil fingerprints' as developmental markers is critical for understanding the evolution of stomatal patterning. Long cell-short cell alternation in the developing leaf epidermis indicates that the stomata are derived from an asymmetric mitosis. Other potential developmental markers include nonrandom stomatal orientation and a range of variation in relative sizes of epidermal cells. Records of occasional giant stomata in fossil bennettites could indicate development of a similar type to early-divergent angiosperms.

  15. Factors and processes governing the C-14 content of carbonate in desert soils

    NASA Technical Reports Server (NTRS)

    Amundson, Ronald; Wang, Yang; Chadwick, Oliver; Trumbore, Susan; Mcfadden, Leslie; Mcdonald, Eric; Wells, Steven; Deniro, Michael

    1994-01-01

    A model is presented describing the factors and processes which determine the measured C-14 ages of soil calcium carbonate. Pedogenic carbonate forms in isotopic equilium with soil CO2. Carbon dioxide in soils is a mixture of CO2 derived from two biological sources: respiration by living plant roots and respiration of microorganisms decomposing soil humus. The relative proportion of these two CO2 sources can greatly affect the initial C-14 content of pedogenic carbonate: the greater the contribution of humus-derived CO2, the greater the initial C-14 age of the carbonate mineral. For any given mixture of CO2 sources, the steady-state (14)CO2 distribution vs. soil depth can be described by a production/diffusion model. As a soil ages, the C-14 age of soil humus increases, as does the steady-state C-14 age of soil CO2 and the initial C-14 age of any pedogenic carbonate which forms. The mean C-14 age of a complete pedogenic carbonate coating or nodule will underestimate the true age of the soil carbonate. This discrepancy increases the older a soil becomes. Partial removal of outer (and younger) carbonate coatings greatly improves the relationship between measured C-14 age and true age. Although the production/diffusion model qualitatively explains the C-14 age of pedogenic carbonate vs. soil depth in many soils, other factors, such as climate change, may contribute to the observed trends, particularily in soils older than the Holocene.

  16. Delineation of temporal variability and governing factors influencing the spatial variability of shallow groundwater chemistry in a tropical sedimentary island

    NASA Astrophysics Data System (ADS)

    Lin, Chin Yik; Abdullah, Mohd Harun; Praveena, Sarva Mangala; Yahaya, Aminatul Hawa Bt; Musta, Baba

    2012-04-01

    SummaryAn attempt has been made to delineate the temporal variability and factors governing the shallow groundwater chemistry using analysis of variance (ANOVA) and multivariate analysis notably R-mode factor (FA) and hierarchical cluster analysis (HCA). Subsequently, geostatistical isoplethic maps were applied to convey better understanding on the distribution of selected groundwater parameters. The Manukan Island's shallow aquifer with sedimentary setting that constantly abstracted for freshwater supply has been selected for this study. One-way ANOVA suggested that neither changes of tide level nor rainfall volume appeared to exert significant influence on the groundwater chemistry of the small island. Rather, the groundwater chemistry was greatly governed by influence from seawater intrusion, which characterized by considerable amount of Ca, Na, and Cl. Such condition was well explained by a Piper diagram, where most plots were situated at the middle diamond shaped diagram, indicating mixing condition. FA likewise revealed that the shallow groundwater receives marked influence from carbonate dissolution and silicate weathering processes, especially boreholes located in the inland area. This can be clearly noted from the distinct groupings of relationships among different factors. HCA classified boreholes into three groups according to their locations in the coastal area, suggesting significant chemical variations between boreholes with distance from coast. Such distribution pattern was particularly evident in the isoplethic map. Overall, it appears that the shallow groundwater in the tropical island is not an appropriate source for drinking water in concern to its exceptionally high salinity and several elevated minor elements (Mn, Pb, and Se). For this, it is suggested that efforts in exploring other alternative sources should be performed outright.

  17. Synergistic effect of multiple predisposing risk factors on the development of bezoars

    PubMed Central

    Kement, Metin; Ozlem, Nuraydin; Colak, Elif; Kesmer, Sadik; Gezen, Cem; Vural, Selahattin

    2012-01-01

    AIM: To describe the clinical characteristics of patients with gastric or intestinal bezoars recently treated in our hospital. METHODS: In this study, a retrospective chart review of consecutive patients with gastrointestinal bezoars, who were treated at the Samsun Education and Research Hospital between January 2006 and March 2011, was conducted. Data on demographic characteristics, clinical presentation, history of risk factors, diagnostic procedures, localization of bezoars, treatment interventions, and postoperative morbidity and mortality rates were collected and evaluated. RESULTS: Forty-two patients [26 (61.9%) males and 16 (31.1%) females] with a mean ± SD (range) age of 55.8 ± 10.5 (37-74) years were enrolled in this study. Thirty-six patients (85.7%) had one or more predisposing risk factors for gastrointestinal bezoars. The most common predisposing risk factor was a history of previous gastric surgery which was identified in 18 patients (42.8%). Twenty three patients (54.8%) had multiple predisposing risk factors. Phytobezoars were identified in all patients except one who had a trichobezoar in the stomach. Non-operative endoscopic fragmentation was performed either initially or after unsuccessful medical treatment in 14 patients with gastric bezoars and was completely successful in 10 patients (71.5%). Surgery was the most frequent treatment method in our study, which was required in 28 patients (66.7%). Intestinal obstruction secondary to bezoars was the most common complication (n = 18, 42.8%) in our study. CONCLUSION: The presence of multiple predisposing factors may create a synergistic effect in the development of bezoars. PMID:22408356

  18. Lateral gas transport in soil adjacent to an old landfill: factors governing gas migration.

    PubMed

    Christophersen, M; Kjeldsen, P

    2001-12-01

    Field experiments investigating lateral gas transport in soil adjacent to an old landfill in Denmark during a one-year period were conducted. A significant seasonal variation, with low concentrations of methane and high concentrations of carbon dioxide in the summer, caused by methane oxidation was observed. There was a good correlation between pressure above the barometric pressure and the methane concentration in the soil, indicating that advective flow was the controlling process. This was confirmed by calculations. Diurnal measurement during a drop in barometric pressure showed that lateral migration of landfill gas was a very dynamic system and the concentrations of LFG at a specific place and depth changed dramatically within a very short time. The experiments showed that change in barometric pressure was an important factor affecting gas migration at the Skellingsted landfill in Denmark.

  19. Edaphic factors do not govern the ectomycorrhizal specificity of Pisonia grandis (Nyctaginaceae).

    PubMed

    Hayward, Jeremy A; Horton, Thomas R

    2012-11-01

    Pisonia grandis (Nyctaginaceae), a widespread tree of Pacific coral atolls and islands, displays one of the more restrictive ranges of ectomycorrhizal (ECM) fungus associates among autotrophic plants. Only five ECM fungi are currently known associates; our study adds one. In many habitats, P. grandis is restricted to large seabird colonies where nitrogen and phosphorus inputs in the form of guano are substantial. It has been suggested that the ECM specificity displayed by P. grandis is the result of the unusual nutrient-rich habitat in which P. grandis grows. On Rota, Commonwealth of the Northern Mariana Islands, P. grandis grows in habitats heavily influenced by guano additions and also in upland forests where seabirds do not roost or nest. To test the hypothesis that the ECM specificity displayed by P. grandis is the result of nutrient-related or toxicity-related factors associated with guano inputs, we sampled P. grandis growing in both guano-rich and guano-poor habitats on Rota, Commonwealth of the Northern Mariana Islands. We identified ECM symbionts of P. grandis from both habitats as well as two symbionts of Intsia bijuga (Fabaceae) from nutrient-rich habitats. We identified three ECM symbionts of P. grandis from Rota; all three were found in both guano-rich and guano-poor habitats. No differences in community diversity were detected between guano-rich and guano-poor habitats. We also detected two ECM fungal species associating with I. bijuga but not associating with P. grandis inside guano-rich habitats. From these results, we infer that edaphic factors are not responsible for limiting the ECM community associating with P. grandis to its observed level of specificity. PMID:22569801

  20. Edaphic factors do not govern the ectomycorrhizal specificity of Pisonia grandis (Nyctaginaceae).

    PubMed

    Hayward, Jeremy A; Horton, Thomas R

    2012-11-01

    Pisonia grandis (Nyctaginaceae), a widespread tree of Pacific coral atolls and islands, displays one of the more restrictive ranges of ectomycorrhizal (ECM) fungus associates among autotrophic plants. Only five ECM fungi are currently known associates; our study adds one. In many habitats, P. grandis is restricted to large seabird colonies where nitrogen and phosphorus inputs in the form of guano are substantial. It has been suggested that the ECM specificity displayed by P. grandis is the result of the unusual nutrient-rich habitat in which P. grandis grows. On Rota, Commonwealth of the Northern Mariana Islands, P. grandis grows in habitats heavily influenced by guano additions and also in upland forests where seabirds do not roost or nest. To test the hypothesis that the ECM specificity displayed by P. grandis is the result of nutrient-related or toxicity-related factors associated with guano inputs, we sampled P. grandis growing in both guano-rich and guano-poor habitats on Rota, Commonwealth of the Northern Mariana Islands. We identified ECM symbionts of P. grandis from both habitats as well as two symbionts of Intsia bijuga (Fabaceae) from nutrient-rich habitats. We identified three ECM symbionts of P. grandis from Rota; all three were found in both guano-rich and guano-poor habitats. No differences in community diversity were detected between guano-rich and guano-poor habitats. We also detected two ECM fungal species associating with I. bijuga but not associating with P. grandis inside guano-rich habitats. From these results, we infer that edaphic factors are not responsible for limiting the ECM community associating with P. grandis to its observed level of specificity.

  1. Multiple roles of tumor necrosis factor-alpha in fracture healing.

    PubMed

    Karnes, Jonathan M; Daffner, Scott D; Watkins, Colleen M

    2015-09-01

    This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications.

  2. Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms

    PubMed Central

    O’Gorman, Cullen; Lucas, Robyn; Taylor, Bruce

    2012-01-01

    Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system commonly affecting young adults. Pathologically, there are patches of inflammation (plaques) with demyelination of axons and oligodendrocyte loss. There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females). These changes suggest a major role for environmental factors in causation of disease. We have reviewed the evidence and potential mechanisms of action for three exposures: vitamin D, Epstein Barr virus and cigarette smoking. Recent advances supporting gene-environment interactions are reviewed. Further research is needed to establish mechanisms of causality in humans and to explore preventative strategies. PMID:23109880

  3. Spatiotemporal Patterns of Evapotranspiration in Response to Multiple Environmental Factors Simulated by the Community Land Model

    SciTech Connect

    Shi, Xiaoying; Mao, Jiafu; Thornton, P.; Huang, Maoyi

    2013-04-25

    Spatiotemporal patterns of evapotranspiration (ET) over the period from 1982 to 2008 are investigated and attributed to multiple environmental factors using the Community Land Model version 4 (CLM4). Our results show that CLM4 captures the spatial distribution and interannual variability of ET well when compared to observation-based estimates. We find that climate dominates the predicted variability in ET. Elevated atmospheric CO2 concentration also plays an important role in modulating the trend of predicted ET over most land areas, and replaces climate to function as the dominant factor controlling ET changes over the North America, South America and Asia regions. Compared to the effect of climate and CO2 concentration, the roles of other factors such as nitrogen deposition, land use change and aerosol deposition are less pronounced and regionally dependent. The aerosol deposition contribution is the third most important factor for trends of ET over Europe, while it has the smallest impact over other regions. As ET is a dominant component of the terrestrial water cycle, our results suggest that environmental factors like elevated CO2, nitrogen and aerosol depositions, and land use change, in addition to climate, could have significant impact on future projections of water resources and water cycle dynamics at global and regional scales.

  4. A Multiple Indicators Multiple Cause (MIMIC) model of respiratory health and household factors in Chinese children: the seven Northeastern cities (SNEC) study.

    PubMed

    Dong, Guang-Hui; Qian, Zhengmin; Fu, Qiang; Wang, Jing; Trevathan, Edwin; Ma, Wenjun; Liu, Miao-Miao; Wang, Da; Ren, Wan-Hui; Ong, Kee-Hean; Ferguson, Tekeda Freeman; Riley, Erin; Simckes, Maayan

    2014-01-01

    In China, with the rapid economic development and improvement of living standards over the past few decades, the household living environment has shifted dramatically. The aim of the present study is to assess the impact of home environment factors on respiratory symptoms and asthma in Chinese children. Investigators analyzed data collected in the 25 districts from the seven Northeastern cities to examine health effects on respiratory symptoms and asthma in 31,049 children aged 2-14 years. Factor analysis was used to reduce 33 children's lifestyle and household variables to six new 'factor' variables. The multiple indicators multiple causes approach was used to examine the relationship between indoor air pollution and respiratory health status, controlling for covariates. Factor analyses generated six factor variables of potential household risk factors from an original list of 33 variables. The respiratory symptoms and asthma were significantly associated with the recent home renovation factor (estimate = 0.076, p < 0.001), pet ownership factor (estimate = 0.095, p < 0.001), environmental tobacco smoke (ETS) exposure factor (estimate = 0.181, p < 0.001) and PVC-flooring factor (estimate = 0.031, p = 0.007). Home ventilation factor was not related to any respiratory condition (estimate = 0.028, p = 0.074). Independent respiratory health effects existed for multiple household environmental factors recent home renovation, pet ownership, ETS, and PVC-flooring. PMID:23440490

  5. On the factors governing the abundance of oxalic acid in tropospheric aerosol particles

    NASA Astrophysics Data System (ADS)

    van Pinxteren, D.; Neusuess, C.; Brüggemann, E.; Gnauk, T.; Müller, K.; Herrmann, H.

    2010-12-01

    Oxalic acid is frequently observed as one of the most abundant single organic compounds in tropospheric particles. Its sources are commonly believed to be of secondary nature. In state-of-the-art multiphase chemistry models, different pathways exist, which can lead to oxalic acid as final product. Anthropogenic hydrocarbon emissions can be photochemically degraded to glyoxal and methyglyoxal, which - after partitioning into deliquescent particles or cloud droplets - are further oxidized via glyoxylic acid to oxalic acid [Herrmann et al., 2005]. A biogenic oxidation pathway starts with isoprene or monoterpene emissions and leads to glycolaldehyde and methylglyoxal via methacrolein and methylvinylketone, followed by aqueous phase oxalic acid formation [Lim et al., 2005]. As suggested by Warneck, 2003, a marine pathway might exist, starting from marine ethene emissions and leading via glycolaldehyde to oxalic acid. The aim of this study was to elucidate from field measurements the importance of each of these pathways. To this aim, oxalic acid concentrations from 144 size-resolved particle samples (5-stage Berner impactor) from different continental and coastal European sampling sites were statistically analyzed using principal component analysis (PCA). Hourly back trajectories were calculated for each sampling interval using the HYSPLIT model [Draxler and Rolph, 2003] and combined in a novel way with global land cover data to yield “residence times” of the sampled air masses above urban, agricultural, forested, and oceanic areas. These residence times served as quantitative proxies for different emission regimes (anthropogenic, biogenic, marine) in the statistical analysis. Additionally, meteorological parameters such as sunflux along the trajectories or mixing layer depth at the sampling site were retrieved from the HYSPLIT output. PCA of the continental dataset retrieved two factors that were connected to the oxalic acid concentrations. A first one showed high

  6. E-government factors to reduce administrative and finance corruption in Arab countries: Case study Iraqi oil sector

    NASA Astrophysics Data System (ADS)

    Mohammed, M. A.; Eman, Y.; Hussein, A. H.; Hasson, A. R.

    2015-12-01

    Arab countries face the corruption issues in its several public organizations. The corruption in these countries is considered as the main challenge. The oil sector is one of the public sectors that have huge level of corruption. However, the Iraqi economy had become dependable on oil sector daring the last three decades, and on the contrary, of what other oil countries did. The capital is considered as one of the essential factor for economic development. The revenues of oil exports will stay the essential source for economic development in Iraq in the future in order to reduce being dependable on oil. Since the beginning of the 3rd thousands, the world witnessed great rise in the demand on oil, but the Iraqi exports of crude oil come to be less than its similarities in the seventeenths of last century. So our oil sector is still in need of deep study. This study focuses on technological technique that can make huge decrease for corruption in oil sector in Iraq. However, e-government is considered as the best techniques that can decrease the corruption. Thus, this study bases on challenges that effect on build successful e-government project in Iraqi oil industry.

  7. Evaluation of the factors governing metal biosorption and metal toxicity in acidic soil isolates

    SciTech Connect

    Pradhan, A.A.

    1992-06-09

    This research project was designed to determine the feasibility of microbial biosorption processes for removing metal ions from aqueous systems. A culture of acidic soil actinomycetes, grown in an aerobic environment in a completely mixed, semibatch culture reactor, was used for the study. The experiments were based on removal of copper and lead from test solutions. The anionic systems tested were nitrate, sulfate, and chloride. To determine the factors influencing biosorption and to characterize metal uptake by cellular and extracellular components of the microbial system, a dialysis testing procedure was developed. The effectiveness of biosorption was influenced by pH, initial concentration of metals, type of anionic system, and organic content of the system. respirometric runs were carried out to identify potential inhibitory effects of metal accumulation on microbial activities. In general, metal accumulation resulted in a decrease in the microbial oxygen uptake rate. Also, a lag phase was observed before the onset of the respiratory activity particularly at concentrations of copper and lead greater than 100 ppM.

  8. Factors governing change in water withdrawals for U.S. industrial sectors from 1997 to 2002.

    PubMed

    Wang, Hui; Small, Mitchell J; Dzombak, David A

    2014-03-18

    The United States Geological Survey (USGS) reports that U.S. water withdrawals have been steady since 1980, but the population and economy have grown since then. This implies that other factors have contributed to offsetting decreases in water withdrawals. Using water withdrawal data from USGS and economic data from Bureau of Economic Analysis (BEA), direct and total water withdrawals were estimated for 134 industrial summary sectors in the 1997 U.S. economic input-output (EIO) table and 136 industrial sectors in the 2002 EIO table. Using structural decomposition analysis (SDA), the change in water withdrawals for the economy from 1997 to 2002 was allocated to changes in population, GDP per capita, water use intensity, production structure, and consumption patterns. The changes in population, GDP per capita, and water use intensity led to increased water withdrawals, while the changes in production structure and consumption patterns decreased water withdrawals from 1997 to 2002. Consumption patterns change was the largest net contributor to the change in water withdrawals. The model was used to predict aggregate changes in total water withdrawals from 2002 to 2010 due to known changes in population and GDP per capita; a more complete model assessment must await release of updated data on USGS water withdrawals and EIO data.

  9. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

    PubMed Central

    Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine

    2015-01-01

    Adult stem cells (SCs) reside in niches which balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, SCs outside their niche often display fate flexibility1-4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult SCs in vivo. Using hair follicle (HF) as model, we map the global chromatin domains of HFSCs and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicenters’) of transcription factor (TF) binding sites change upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicenters, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, HFSCs dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicenters, enabling them to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of HFSC super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense TF-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status, but also stemness, plasticity in transitional states and differentiation. PMID:25799994

  10. Familial monoclonal gammopathy of undetermined significance and multiple myeloma: epidemiology, risk factors, and biological characteristics

    PubMed Central

    Greenberg, Alexandra J.; Rajkumar, S. Vincent

    2012-01-01

    Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), is one of the most common premalignant conditions in the general population. The cause of MGUS is largely unknown. Recent studies show that there is an increased prevalence of MGUS in blood relatives of persons with lymphoproliferative and plasma cell proliferative disorders, suggesting presence of shared underlying genetic influences. In the past few years, additional studies have examined risk factors and biologic characteristics that may contribute to the increased prevalence of MGUS among relatives of probands with MGUS, MM, and other blood malignancies. This article reviews the known epidemiology and risk factors for familial MGUS and myeloma, the risk of lymphoproliferative disorders and other malignancies among blood-relatives of patients with MGUS and MM, and discusses future directions for research. PMID:22354002

  11. Risk factors for neutropenia with lenalidomide plus dexamethasone therapy for multiple myeloma.

    PubMed

    Mitani, Y; Usami, E; Kimura, M; Nakao, T; Okada, K; Matsuoka, T; Kokuryou, T; Yoshimura, T; Yamakawa, M

    2016-06-01

    Neutropenia may develop as an adverse event in patients with multiple myeloma receiving lenalidomide (LEN) plus dexamethasone (DEX) therapy. In the present study, we examined the risk factors associated with grade 3/4 neutropenia during the first cycle of LEN plus DEX therapy. We observed that hemoglobin level (≤ 8.5 g/dl) was a significant risk factor for grade 3/4 neutropenia during the first cycle of therapy (odds ratio: 19.40; 95% confidence interval: 2.68-141.00; p < 0.01). thus, our findings suggest that determining the hemoglobin level could be useful in the risk management for neutropenia in patients receiving LEN plus DEX therapy. PMID:27455556

  12. Reversal of Ischemic Cardiomyopathy with Sca-1+ Stem Cells Modified with Multiple Growth Factors

    PubMed Central

    Li, Ning; Pasha, Zeeshan; Ashraf, Muhammad

    2014-01-01

    Background We hypothesized that bone marrow derived Sca-1+ stem cells (BM Sca-1+) transduced with multiple therapeutic cytokines with diverse effects will induce faster angiomyogenic differentiation in the infarcted myocardium. Methods and Results BM Sca-1+ were purified from transgenic male mice expressing GFP. Plasmids encoding for select quartet of growth factors, i.e., human IGF-1, VEGF, SDF-1α and HGF were prepared and used for genetic modification of Sca-1+ cells (GFSca-1+). Scramble transfected cells (ScSca-1+) were used as a control. RT-PCR and western blotting showed significantly higher expression of the growth factors in GFSca-1+. Besides the quartet of the therapeutic growth factors, PCR based growth factor array showed upregulation of multiple angiogenic and prosurvival factors such as Ang-1, Ang-2, MMP9, Cx43, BMP2, BMP5, FGF2, and NGF in GFSca-1+ (p<0.01 vs ScSca-1+). LDH and TUNEL assays showed enhanced survival of GFSca-1+ under lethal anoxia (p<0.01 vs ScSca-1+). MTS assay showed significant increased cell proliferation in GFSca-1+ (p<0.05 vs ScSca-1+). For in vivo study, female mice were grouped to receive the intramyocardial injection of 15 μl DMEM without cells (group-1) or containing 2.5×105 ScSca-1+ (group-2) or GFSca-1+ (group-3) immediately after coronary artery ligation. As indicated by Sry gene, a higher survival of GFSca-1+ in group-3 on day4 (2.3 fold higher vs group-2) was observed with massive mobilization of stem and progenitor cells (cKit+, Mdr1+, Cxcr4+ cells). Heart tissue sections immunostained for actinin and Cx43 at 4 weeks post engraftment showed extensive myofiber formation and expression of gap junctions. Immunostaining for vWF showed increased blood vessel density in both peri-infarct and infarct regions in group-3. Infarct size was attenuated and the global heart function was improved in group-3 as compared to group-2. Conclusions Administration of BM Sca-1+ transduced with multiple genes is a novel approach to treat

  13. Multiple Landscape Factors Affect the Resilience of a Mixed Land Cover Watershed

    NASA Astrophysics Data System (ADS)

    Golden, H. E.; Lane, C.; Prues, A. G.; D'Amico, E.

    2015-12-01

    Human activities can stimulate the physical and chemical properties of streams to move beyond their background conditions, thereby facilitating the transition of these factors to stressors that affect watershed resilience. This is particularly true in mixed land cover watersheds. We quantify and explore the statistical nonlinear relationships between watershed and buffer-scale factors and nutrient (nitrite-nitrate (NO2-NO3), total Kjeldahl nitrogen (TKN), total phosphorus (TP)) concentrations, in addition to a multi-metric Index of Biotic Integrity (IBI), in a mesoscale mixed land cover watershed. Our goal is to contribute to a better understanding of the potentially numerous landscape and near-stream hydrological and biogeochemical factors that affect watershed resiliency - as inferred from in-stream nutrient levels and biological condition. We used a boosted regression tree approach, which quantifies nonlinear relationships and variable interactions, to develop watershed and 200 m buffer scale models for each chemical constituent and the annual IBI score. We developed nutrient models for the spring and summer seasons. Two primary factors - location within the watershed and percentage of urban land cover in the watershed or buffer - emerged as important explanatory variables in most nutrient and IBI models. Geographic location (i.e., latitude and longitude) interacted with other factors to explain the variability in summer NO2-NO3 concentrations and IBI scores and suggested that location might be associated with indicators of sources (e.g., land cover) and runoff potential (e.g., soil and topographic factors). Runoff indicators (e.g., Hydrologic Soil Group D and Topographic Wetness Indices) explained a substantial portion of the variability in nutrient concentrations as did point sources for TP in the summer months. Our overall approach confirms that it is important to consider multiple and often interacting factors when managing for watershed resilience.

  14. Goldfish (Carassius auratus L.) as a model system to study the growth factors, receptors and transcription factors that govern myelopoiesis in fish.

    PubMed

    Katzenback, Barbara A; Katakura, Fumihiko; Belosevic, Miodrag

    2016-05-01

    The process of myeloid cell development (myelopoiesis) in fish has mainly been studied in three cyprinid species: zebrafish (Danio rerio), ginbuna carp (Carassius auratus langsdorfii) and goldfish (C. auratus, L.). Our studies on goldfish myelopoiesis have utilized in vitro generated primary kidney macrophage (PKM) cultures and isolated primary kidney neutrophils (PKNs) cultured overnight to study the process of macrophage (monopoiesis) and neutrophil (granulopoiesis) development and the key growth factors, receptors, and transcription factors that govern this process in vitro. The PKM culture system is unique in that all three subpopulations of macrophage development, namely progenitor cells, monocytes, and mature macrophages, are simultaneously present in culture unlike mammalian systems, allowing for the elucidation of the complex mixture of cytokines that regulate progressive and selective macrophage development from progenitor cells to fully functional mature macrophages in vitro. Furthermore, we have been able to extend our investigations to include the development of erythrocytes (erythropoiesis) and thrombocytes (thrombopoiesis) through studies focusing on the progenitor cell population isolated from the goldfish kidney. Herein, we review the in vitro goldfish model systems focusing on the characteristics of cell sub-populations, growth factors and their receptors, and transcription factors that regulate goldfish myelopoiesis. PMID:26546240

  15. Goldfish (Carassius auratus L.) as a model system to study the growth factors, receptors and transcription factors that govern myelopoiesis in fish.

    PubMed

    Katzenback, Barbara A; Katakura, Fumihiko; Belosevic, Miodrag

    2016-05-01

    The process of myeloid cell development (myelopoiesis) in fish has mainly been studied in three cyprinid species: zebrafish (Danio rerio), ginbuna carp (Carassius auratus langsdorfii) and goldfish (C. auratus, L.). Our studies on goldfish myelopoiesis have utilized in vitro generated primary kidney macrophage (PKM) cultures and isolated primary kidney neutrophils (PKNs) cultured overnight to study the process of macrophage (monopoiesis) and neutrophil (granulopoiesis) development and the key growth factors, receptors, and transcription factors that govern this process in vitro. The PKM culture system is unique in that all three subpopulations of macrophage development, namely progenitor cells, monocytes, and mature macrophages, are simultaneously present in culture unlike mammalian systems, allowing for the elucidation of the complex mixture of cytokines that regulate progressive and selective macrophage development from progenitor cells to fully functional mature macrophages in vitro. Furthermore, we have been able to extend our investigations to include the development of erythrocytes (erythropoiesis) and thrombocytes (thrombopoiesis) through studies focusing on the progenitor cell population isolated from the goldfish kidney. Herein, we review the in vitro goldfish model systems focusing on the characteristics of cell sub-populations, growth factors and their receptors, and transcription factors that regulate goldfish myelopoiesis.

  16. NAC transcription factors in plant multiple abiotic stress responses: progress and prospects.

    PubMed

    Shao, Hongbo; Wang, Hongyan; Tang, Xiaoli

    2015-01-01

    Abiotic stresses adversely affect plant growth and agricultural productivity. According to the current climate prediction models, crop plants will face a greater number of environmental stresses, which are likely to occur simultaneously in the future. So it is very urgent to breed broad-spectrum tolerant crops in order to meet an increasing demand for food productivity due to global population increase. As one of the largest families of transcription factors (TFs) in plants, NAC TFs play vital roles in regulating plant growth and development processes including abiotic stress responses. Lots of studies indicated that many stress-responsive NAC TFs had been used to improve stress tolerance in crop plants by genetic engineering. In this review, the recent progress in NAC TFs was summarized, and the potential utilization of NAC TFs in breeding abiotic stress tolerant transgenic crops was also be discussed. In view of the complexity of field conditions and the specificity in multiple stress responses, we suggest that the NAC TFs commonly induced by multiple stresses should be promising candidates to produce plants with enhanced multiple stress tolerance. Furthermore, the field evaluation of transgenic crops harboring NAC genes, as well as the suitable promoters for minimizing the negative effects caused by over-expressing some NAC genes, should be considered. PMID:26579152

  17. Hydrogeological factors affecting the multiple plumes of chlorinated contaminants in an industrial complex, Wonju, Korea

    NASA Astrophysics Data System (ADS)

    Yang, J.; Kaown, D.; Lee, H.; Lee, K.

    2010-12-01

    Apparent plume attenuations of multiple chlorinated contaminants such as TCE, carbon tetrachloride, and its daughter products at an industrial complex, Wonju, Korea were examined through various hydraulic tests and six rounds of groundwater quality analyses. Aquifer media properties and hydrogeologic factors affecting the distribution and attenuation of multiple contaminants were investigated and key attributes were evaluated. The study area has vertically heterogeneous properties from top alluvial layer to crystalline rocks while the weathered fractured layer above intact Jurassic biotite granite acts as the main layer for groundwater flow and aqueous phase multiple contaminants migration. Aerial heterogeneity in surface conditions plays an important role for groundwater recharge because the industrial complex is mostly paved by asphalt and concrete. Due to limited recharge area and concentrated precipitation in summer season, seasonal effects of contaminant plume distribution diminish as the distance increase from the area of recharge. This study analyzed how differently the solute and contaminant concentrations response to the seasonal recharge. For the analyses, the study site was divided into three zones and four transects were established. Groundwater and solute mass balances were estimated by computing groundwater and solute mass flux through transects. The effects of groundwater pumping, groundwater flow and contaminant degradation were examined to simulate the solutes and contaminant concentrations. General tendency of the water quality and contaminant concentration were reproducible with the effects of major components such as groundwater recharge, pumping and estimated degradation rate.

  18. Systematic review of randomised controlled trials of multiple risk factor interventions for preventing coronary heart disease.

    PubMed Central

    Ebrahim, S.; Smith, G. D.

    1997-01-01

    OBJECTIVE: To assess the effectiveness of multiple risk factor intervention in reducing cardiovascular risk factors, total mortality, and mortality from coronary heart disease among adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials in workforces and in primary care in which subjects were randomly allocated to more than one of six interventions (stopping smoking, exercise, dietary advice, weight control, antihypertensive drugs, and cholesterol lowering drugs) and followed up for at least six months. SUBJECTS: Adults aged 17-73 years, 903000 person years of observation were included in nine trials with clinical event outcomes and 303000 person years in five trials with risk factor outcomes alone. MAIN OUTCOME MEASURES: Changes in systolic and diastolic blood pressure, smoking rates, blood cholesterol concentrations, total mortality, and mortality from coronary heart disease. RESULTS: Net decreases in systolic and diastolic blood pressure, smoking prevalence, and blood cholesterol were 4.2 mm Hg (SE 0.19 mm Hg), 2.7 mm Hg (0.09 mm Hg), 4.2% (0.3%), and 0.14 mmol/l (0.01 mmol/l) respectively. In the nine trials with clinical event end points the pooled odds ratios for total and coronary heart disease mortality were 0.97 (95% confidence interval 0.92 to 1.02) and 0.96 (0.88 to 1.04) respectively. Statistical heterogeneity between the studies with respect to changes in mortality and risk factors was due to trials focusing on hypertensive participants and those using considerable amounts of drug treatment, with only these trials showing significant reductions in mortality. CONCLUSIONS: The pooled effects of multiple risk factor intervention on mortality were insignificant and a small, but potentially important, benefit of treatment (about a 10% reduction in mortality) may have been missed. Changes in risk factors were modest, were related to the amount of pharmacological treatment used, and in some cases may have been overestimated

  19. Multiple anthelmintic resistance and the possible contributory factors in Beetal goats in an irrigated area (Pakistan).

    PubMed

    Saeed, Muhammad; Iqbal, Zafar; Jabbar, Abdul; Masood, Sabiqaa; Babar, Wasim; Saddiqi, Hafiz A; Yaseen, Muhammad; Sarwar, Muhammad; Arshad, Muhammad

    2010-04-01

    This paper presents the first report of multiple anthelmintic resistance in the gastrointestinal nematodes of goats and its possible contributory factors in an irrigated area (Pakistan). A total of 18 privately owned Beetal goat flocks were selected in order to determine the anthelmintic resistance against commonly used anthelmintics. Forty to 48 animals from each flock were selected according to their weight and egg count. The three anthelmintics viz., oxfendazole, levamisole and ivermectin, were given to three groups at manufacturer's recommended dose while one group was kept as untreated control. Anthelmintic resistance was determined through faecal egg count reduction and egg hatch tests while assessment of the contributory factors of anthelmintic resistance was measured through the rural participatory approach. Faecal egg count reduction test revealed high prevalence of anthelmintic resistance (83.3%) and it was either single (levamisole) or multiple (oxfendazole and levamisole). Egg hatch test confirmed the resistance against oxfendazole as detected with faecal egg count reduction test. None of the goat flocks was resistant to ivermectin. Copro-cultures revealed that Haemonchus contortus, Trichostrongylus colubriformis and Teladorsagia circumcincta were the most common species exhibiting resistance to levamisole and oxfendazole. Step-wise logistic regression of the data on worm control practices revealed significant role of under-dosing, low-protein diets, healthcare supervision by the traditional healers and mass treatments.

  20. Hydroecological factors governing surface water flow on a low-gradient floodplain

    NASA Astrophysics Data System (ADS)

    Harvey, Judson W.; Schaffranek, Raymond W.; Noe, Gregory B.; Larsen, Laurel G.; Nowacki, Daniel J.; O'Connor, Ben L.

    2009-03-01

    Interrelationships between hydrology and aquatic ecosystems are better understood in streams and rivers compared to their surrounding floodplains. Our goal was to characterize the hydrology of the Everglades ridge and slough floodplain ecosystem, which is valued for the comparatively high biodiversity and connectivity of its parallel-drainage features but which has been degraded over the past century in response to flow reductions associated with flood control. We measured flow velocity, water depth, and wind velocity continuously for 3 years in an area of the Everglades with well-preserved parallel-drainage features (i.e., 200-m wide sloughs interspersed with slightly higher elevation and more densely vegetated ridges). Mean daily flow velocity averaged 0.32 cm s-1 and ranged between 0.02 and 0.79 cm s-1. Highest sustained velocities were associated with flow pulses caused by water releases from upstream hydraulic control structures that increased flow velocity by a factor of 2-3 on the floodplain for weeks at a time. The highest instantaneous measurements of flow velocity were associated with the passage of Hurricane Wilma in 2005 when the inverse barometric pressure effect increased flow velocity up to 5 cm s-1 for several hours. Time-averaged flow velocities were 29% greater in sloughs compared to ridges because of marginally higher vegetative drag in ridges compared to sloughs, which contributed modestly (relative to greater water depth and flow duration in sloughs compared to ridges) to the predominant fraction (86%) of total discharge through the landscape occurring in sloughs. Univariate scaling relationships developed from theory of flow through vegetation, and our field data indicated that flow velocity increases with the square of water surface slope and the fourth power of stem diameter, decreases in direct proportion with increasing frontal area of vegetation, and is unrelated to water depth except for the influence that water depth has in controlling

  1. Hydroecological factors governing surface water flow on a low-gradient floodplain

    USGS Publications Warehouse

    Harvey, J.W.; Schaffranek, R.W.; Noe, G.B.; Larsen, L.G.; Nowacki, D.J.; O'Connor, B.L.

    2009-01-01

    Interrelationships between hydrology and aquatic ecosystems are better understood in streams and rivers compared to their surrounding floodplains. Our goal was to characterize the hydrology of the Everglades ridge and slough floodplain ecosystem, which is valued for the comparatively high biodiversity and connectivity of its parallel-drainage features but which has been degraded over the past century in response to flow reductions associated with flood control. We measured flow velocity, water depth, and wind velocity continuously for 3 years in an area of the Everglades with well-preserved parallel-drainage features (i.e., 200-m wide sloughs interspersed with slightly higher elevation and more densely vegetated ridges). Mean daily flow velocity averaged 0.32 cm s-1 and ranged between 0.02 and 0.79 cm s-1. Highest sustained velocities were associated with flow pulses caused by water releases from upstream hydraulic control structures that increased flow velocity by a factor of 2-3 on the floodplain for weeks at a time. The highest instantaneous measurements of flow velocity were associated with the passage of Hurricane Wilma in 2005 when the inverse barometric pressure effect increased flow velocity up to 5 cm s-1 for several hours. Time-averaged flow velocities were 29% greater in sloughs compared to ridges because of marginally higher vegetative drag in ridges compared to sloughs, which contributed modestly (relative to greater water depth and flow duration in sloughs compared to ridges) to the predominant fraction (86%) of total discharge through the landscape occurring in sloughs. Univariate scaling relationships developed from theory of flow through vegetation, and our field data indicated that flow velocity increases with the square of water surface slope and the fourth power of stem diameter, decreases in direct proportion with increasing frontal area of vegetation, and is unrelated to water depth except for the influence that water depth has in controlling

  2. Associated Risk Factors of STIs and Multiple Sexual Relationships among Youths in Malawi

    PubMed Central

    N, Wilson Chialepeh; A, Sathiyasusuman

    2015-01-01

    Background Having unprotected sex with multiple sexual partners (MSP) is the greatest risk factor for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) among youths. Young people with MSPs are less likely to use a condom and the greater the risk for STIs. This study examines the associated risk factors of STIs and multiple sexual partnerships among youths aged 15–24 years. Data and Methods The Malawi Demographic Health Survey 2010 data was used. Out of a sample of 2,987 males and 9,559 females aged 15–24 years, 2,026 males and 6,470 females were considered in the study. Chi square test and logistic regression techniques were performed. Analysis was performed using Statistical Package for Social Sciences (SPSS) version 22. Findings The results indicate that 1,399 (69.0%) males and 2,290 (35.4%) females reported multiple sexual partnerships (MSP). Within the rural area, females (n = 1779) were more likely to report MSP than males (n = 1082) and within the urban areas, a higher proportion of females (n = 511) still reported MSP, with males (n = 316). About 78% rural females aged 20–24 years, and about 79% rural males aged 15–19 years reported MSP. The likelihood of MSP was higher among females in the poorest households (OR = 1.31), being married (OR = 5.71) and Catholic males (OR = 1.63), who were married (OR = 1.59). Catholic males (OR = 1.82) in the rural areas, who were married (OR = 1.80) and rural females in the northern region (OR = 1.26) were more likely to have MSP. The odds ratios were higher among urban females in the poorest (OR = 3.45) households who were married (OR = 4.22). Conclusions Having more than one sexual partner increases the risk of STIs and sexuality education programs should be introduced that emphasize the danger that surrounds MSP. PMID:26248328

  3. Population Heterogeneity in the Salience of Multiple Risk Factors for Adolescent Delinquency

    PubMed Central

    Lanza, Stephanie T.; Cooper, Brittany R.; Bray, Bethany C.

    2014-01-01

    Purpose To present mixture regression analysis as an alternative to more standard regression analysis for predicting adolescent delinquency. We demonstrate how mixture regression analysis allows for the identification of population subgroups defined by the salience of multiple risk factors. Methods We identified population subgroups (i.e., latent classes) of individuals based on their coefficients in a regression model predicting adolescent delinquency from eight previously established risk indices drawn from the community, school, family, peer, and individual levels. The study included N = 37,763 tenth-grade adolescents who participated in the Communities that Care Youth Survey. Standard, zero-inflated, and mixture Poisson and negative binomial regression models are considered. Results Standard and mixture negative binomial regression models are selected as optimal. The five-class regression model is interpreted based on the class-specific regression coefficients, indicating that risk factors have varying salience across classes of adolescents. Conclusions Standard regression shows that all risk factors are significantly associated with delinquency. Mixture regression provides more nuanced information, suggesting a unique set of risk factors that are salient for different subgroups of adolescents. Implications for the design of subgroup-specific interventions are discussed. PMID:24231260

  4. Influence of multiple dynamic factors on the performance of myoelectric pattern recognition.

    PubMed

    Khushaba, Rami N; Al-Timemy, Ali; Kodagoda, Sarath

    2015-08-01

    Hand motion classification using surface Electromyogram (EMG) signals has been widely studied for the control of powered prosthetics in laboratory conditions. However, clinical applicability has been limited, as imposed by factors like electrodes shift, variations in the contraction force levels, forearm rotation angles, change of limb position and many other factors that all affect the EMG pattern recognition performance. While the impact of several of these factors on EMG parameter estimation and pattern recognition has been considered individually in previous studies, a minimum number of experiments were reported to study the influence of multiple dynamic factors. In this paper, we investigate the combined effect of varying forearm rotation angles and contraction force levels on the robustness of EMG pattern recognition, while utilizing different time-and-frequency based feature extraction methods. The EMG pattern recognition system has been validated on a set of 11 subjects (ten intact-limbed and one bilateral transradial amputee) performing six classes of hand motions, each with three different force levels, each at three different forearm rotation angles, with six EMG electrodes plus an accelerometer on the subjects' forearm. Our results suggest that the performance of the learning algorithms can be improved with the Time-Dependent Power Spectrum Descriptors (TD-PSD) utilized in our experiments, with average classification accuracies of up to 90% across all subjects, force levels, and forearm rotation angles.

  5. Multiple risk factors in the development of externalizing behavior problems: Group and individual differences

    PubMed Central

    DEATER–DECKARD, KIRBY; DODGE, KENNETH A.; BATES, JOHN E.; PETTIT, GREGORY S.

    2009-01-01

    The aim of this study was to test whether individual risk factors as well as the number of risk factors (cumulative risk) predicted children’s externalizing behaviors over middle childhood. A sample of 466 European American and 100 African American boys and girls from a broad range of socioeconomic levels was followed from age 5 to 10 years. Twenty risk variables from four domains (child, sociocultural, parenting, and peer-related) were measured using in-home interviews at the beginning of the study, and annual assessments of externalizing behaviors were conducted. Consistent with past research, individual differences in externalizing behavior problems were stable over time and were related to individual risk factors as well as the number of risk factors present. Particular risks accounted for 36% to 45% of the variance, and the number of risks present (cumulative risk status) accounted for 19% to 32% of the variance, in externalizing outcomes. Cumulative risk was related to subsequent externalizing even after initial levels of externalizing had been statistically controlled. All four domains of risk variables made significant unique contributions to this statistical prediction, and there were multiple clusters of risks that led to similar outcomes. There was also evidence that this prediction was moderated by ethnic group status, most of the prediction of externalizing being found for European American children. However, this moderation effect varied depending on the predictor and outcome variables included in the model. PMID:9741678

  6. Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up

    SciTech Connect

    Croft, Stephen; Evans, Louise G; Schear, Melissa A

    2010-01-01

    In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build

  7. Modelling University Governance

    ERIC Educational Resources Information Center

    Trakman, Leon

    2008-01-01

    Twentieth century governance models used in public universities are subject to increasing doubt across the English-speaking world. Governments question if public universities are being efficiently governed; if their boards of trustees are adequately fulfilling their trust obligations towards multiple stakeholders; and if collegial models of…

  8. Simultaneous Non-Negative Matrix Factorization for Multiple Large Scale Gene Expression Datasets in Toxicology

    PubMed Central

    Lee, Clare M.; Mudaliar, Manikhandan A. V.; Haggart, D. R.; Wolf, C. Roland; Miele, Gino; Vass, J. Keith; Higham, Desmond J.; Crowther, Daniel

    2012-01-01

    Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process. PMID:23272042

  9. A cytokine gene screen uncovers SOCS1 as genetic risk factor for multiple sclerosis.

    PubMed

    Vandenbroeck, K; Alvarez, J; Swaminathan, B; Alloza, I; Matesanz, F; Urcelay, E; Comabella, M; Alcina, A; Fedetz, M; Ortiz, M A; Izquierdo, G; Fernandez, O; Rodriguez-Ezpeleta, N; Matute, C; Caillier, S; Arroyo, R; Montalban, X; Oksenberg, J R; Antigüedad, A; Aransay, A

    2012-01-01

    Cytokine and cytokine receptor genes, including IL2RA, IL7R and IL12A, are known risk factors for multiple sclerosis (MS). Excitotoxic oligodendroglial death mediated by glutamate receptors contributes to demyelinating reactions. In the present study, we screened 368 single-nucleotide polymorphisms (SNPs) in 55 genes or gene clusters coding for cytokines, cytokine receptors, suppressors of cytokine signaling (SOCS), complement factors and glutamate receptors for association with MS in a Spanish-Basque resident population. Top-scoring SNPs were found within or nearby the genes coding for SOCS-1 (P=0.0005), interleukin-28 receptor, alpha chain (P=0.0008), oncostatin M receptor (P=0.002) and interleukin-22 receptor, alpha 2 (IL22RA2; P=0.003). The SOCS1 rs243324 variant was validated as risk factor for MS in a separate cohort of 3919 MS patients and 4003 controls (combined Cochran-Mantel-Haenszel P=0.00006; odds ratio (OR)=1.13; 95% confidence interval (CI)=1.07-1.20). In addition, the T allele of rs243324 was consistently increased in relapsing-remitting/secondary progressive versus primary-progressive MS patients, in each of the six data sets used in this study (P(CMH)=0.0096; OR=1.24; 95% CI 1.05-1.46). The association with SOCS1 appears independent from the chr16MS risk locus CLEC16A.

  10. The environmental risk factors in multiple sclerosis susceptibility: A case-control study

    PubMed Central

    Shaygannejad, Vahid; Rezaie, Nooshin; Paknahad, Zamzam; Ashtari, Freshteh; Maghzi, Helia

    2016-01-01

    Background: Multiple sclerosis (MS) is a demyelinating and degenerating disease which involves central nervous system. Environmental risk factors have a key role in MS susceptibility. Here we aim to investigate different risk factors effect on MS susceptibility in a large population of MS patients in Isfahan, Iran. Materials and Methods: This study is a cross-sectional hospital-based study, which was conducted on a large group of MS patients registered in Kashani hospital and a control group from normal healthy population. Demographic data, age at onset of the disease, history of viral infections, vaccination, history of trauma to head, recent stressful events, alimentation, familial history, method of delivery (caesarean section, normal vaginal delivery), disability score and history of smoking were gathered using a designed questionnaire. Results: Totally 536 MS patient with the mean age of 34.37 ± 9.22 and 399 individuals from healthy population with the mean age of 32.53 ± 9.91 were recruited. Significant difference in history of measles infection (control = 15.5%, case = 22.4%, P = 0.009), consumption of dairy products (case = 56.6%, control = 67.5%, P = 0.01) and major stressful life events (case = 62.2%, control = 52.7%, P < 0.05) between these two groups were demonstrated. Conclusion: A significant relation between stress, history of infection and milk consumption was reached that highlights the importance of environmental risk factors in MS pathogenesis. PMID:27376037

  11. Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

    PubMed Central

    Won, Eun-Jeong; Kim, Hye-Ran; Choi, Hyun-Jung; Park, Hye-Ri; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

    2014-01-01

    We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (≥68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. PMID:24967406

  12. [Multiple stepwise regression analysis of etiological factors of esophageal cancer in Cixian county].

    PubMed

    Hou, J

    1989-01-01

    Cixian county, one of the high-risk counties of esophageal cancer in the world, has a standardized mortality of 142.19/10(5) population, 1969-1971. The incidence of esophageal cancer had dropped year by year from 1974 to 1982. The significance of the incidence tendency was studied. The results are highly significant (P less than 0.001). The causative factors of esophageal cancer including five independent variables: X1 (number of people taking sanitized water), X2 (number of people on pickled Chinese cabbage), X3 (annual output of fruit), X4 (annual output of fresh vegetable) and X5 (annual output of sweet potato) and one dependent variable Y (morbidity of esophageal cancer) were studied by correlative analysis and multiple stepwise regression. Three correlative factors (X1, X2, and X5) with significant effect on the esophageal cancer were selected from the five suspected factors. The result indicated that taking sanitized water, reducing the number of people on pickled Chinese cabbage, changing the structure of food and keeping the nutrient balance, might decrease the incidence of esophageal cancer. PMID:2789130

  13. Multiple factors contribute to anautogenous reproduction by the mosquito Aedes aegypti.

    PubMed

    Gulia-Nuss, Monika; Elliot, Anne; Brown, Mark R; Strand, Michael R

    2015-11-01

    Aedes aegypti is an anautogenous mosquito that must blood feed on a vertebrate host to produce and lay a clutch of eggs. The rockpool mosquito, Georgecraigius atropalpus, is related to A. aegypti but is a facultatively autogenous species that produces its first clutch of eggs shortly after emerging without blood feeding. Consumption of a blood meal by A. aegypti triggers the release of ovary ecdysteroidogenic hormone (OEH) and insulin-like peptide 3 (ILP3) from the brain, which stimulate egg formation. OEH and ILP3 also stimulate egg formation in G. atropalpus but are released at eclosion independently of blood feeding. These results collectively suggest that blood meal dependent release of OEH and ILP3 is one factor that prevents A. aegypti from reproducing autogenously. Here, we examined two other factors that potentially inhibit autogeny in A. aegypti: teneral nutrient reserves and the ability of OEH and ILP3 to stimulate egg formation in the absence of blood feeding. Measures of nutrient reserves showed that newly emerged A. aegypti females had similar wet weights but significantly lower protein and glycogen reserves than G. atropalpus females when larvae were reared under identical conditions. OEH stimulated non-blood fed A. aegypti females to produce ecdysteroid hormone and package yolk into oocytes more strongly than ILP3. OEH also reduced host seeking and blood feeding behavior, yet females produced few mature eggs. Overall, our results indicate that multiple factors prevent A. aegypti from reproducing autogenously.

  14. Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension.

    PubMed

    Pravenec, M; Zidek, V; Simakova, M; Kren, V; Krenova, D; Horky, K; Jachymova, M; Mikova, B; Kazdova, L; Aitman, T J; Churchill, P C; Webb, R C; Hingarh, N H; Yang, Y; Wang, J M; Lezin, E M; Kurtz, T W

    1999-06-01

    Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.

  15. Testing the facilitation–competition paradigm under the stress-gradient hypothesis: decoupling multiple stress factors

    PubMed Central

    Kawai, Takashi; Tokeshi, Mutsunori

    2007-01-01

    While the facilitation–competition paradigm under the stress-gradient hypothesis has received recent attention, its rigorous testing is yet to be explored. Most of the studies have considered a switch in the net interactions from competition to facilitation with increasing environmental stress as primary evidence supporting the hypothesis, though few studies examined changes in interaction along a full range of a stress gradient. Here, we have conceptualized possible variations in the patterns of change in interaction strength along such gradient. Based on this, we empirically evaluated the temporal shift in the interaction between two marine sessile animals, goose barnacles (Capitulum mitella) and mussels (Septifer virgatus), under multiple stress factors. The net effect of goose barnacles on mussel survivorship was positively related to the total stress gradient encompassing two stress factors, physical disturbance and thermal stress, while no negative value occurred even under mild conditions. When the two stress factors were treated separately, however, the net effect demonstrated apparently different patterns: monotonic increase with physical disturbance versus a quasi-asymptotic pattern (no change over a wide range) with thermal stress. These variable situations have not previously been recognized in this discipline, and the present study emphasizes the importance of an integrative and mechanistic approach to testing and deciphering the facilitation–competition paradigm. PMID:17686725

  16. Testing the facilitation-competition paradigm under the stress-gradient hypothesis: decoupling multiple stress factors.

    PubMed

    Kawai, Takashi; Tokeshi, Mutsunori

    2007-10-01

    While the facilitation-competition paradigm under the stress-gradient hypothesis has received recent attention, its rigorous testing is yet to be explored. Most of the studies have considered a switch in the net interactions from competition to facilitation with increasing environmental stress as primary evidence supporting the hypothesis, though few studies examined changes in interaction along a full range of a stress gradient. Here, we have conceptualized possible variations in the patterns of change in interaction strength along such gradient. Based on this, we empirically evaluated the temporal shift in the interaction between two marine sessile animals, goose barnacles (Capitulum mitella) and mussels (Septifer virgatus), under multiple stress factors. The net effect of goose barnacles on mussel survivorship was positively related to the total stress gradient encompassing two stress factors, physical disturbance and thermal stress, while no negative value occurred even under mild conditions. When the two stress factors were treated separately, however, the net effect demonstrated apparently different patterns: monotonic increase with physical disturbance versus a quasi-asymptotic pattern (no change over a wide range) with thermal stress. These variable situations have not previously been recognized in this discipline, and the present study emphasizes the importance of an integrative and mechanistic approach to testing and deciphering the facilitation-competition paradigm.

  17. Shared Service Center vs. Shared Service Network: A Multiple Case Study Analysis of Factors Impacting on Shared Service Configurations

    NASA Astrophysics Data System (ADS)

    Becker, Jörg; Niehaves, Björn; Krause, Andreas

    Shared services have proven to be a key element when it comes to increasing government efficiency by collaboration. Here, we seek to investigate into the shared services phenomenon in the context of government reforms. For this purpose, an interview and document analysis-based multiple case study has been conducted in Germany. The qualitative analysis covers two shared service implementations on the local government level and identifies important preconditions for shared service emergence, namely cost pressure as motive, the existence of key actors promoting the topic and the existence of prior cooperation. Moreover, it is shown that the structure of such previous cooperation determines, if shared services are being organised in a centralised (shared service centre) or decentralised format (shared service network).

  18. Spatially distributed influence of agro-environmental factors governing nitrate fate and transport in an irrigated stream-aquifer system

    NASA Astrophysics Data System (ADS)

    Bailey, R. T.; Ahmadi, M.; Gates, T. K.; Arabi, M.

    2015-12-01

    Elevated levels of nitrate (NO3) in groundwater systems pose a serious risk to human populations and natural ecosystems. As part of an effort to remediate NO3 contamination in irrigated stream-aquifer systems, this study elucidates agricultural and environmental parameters and processes that govern NO3 fate and transport at the regional (500 km2), local (50 km2), and field scales (< 1 km2). Specifically, the revised Morris sensitivity analysis method was applied to a finite-difference nitrogen cycling and reactive transport model of a regional-scale study site in the lower Arkansas River valley in southeastern Colorado. The method was used to rank the influence of anthropogenic activities and natural chemical processes on NO3 groundwater concentration, NO3 mass leaching, and NO3 mass loading to the Arkansas River from the aquifer. Sensitivity indices were computed for the entire study area in aggregate as well as each canal command area, crop type, and individual grid cells. Results suggest that fertilizer loading, crop uptake, and heterotrophic denitrification govern NO3 fate and transport for the majority of the study area, although their order of influence on NO3 groundwater concentration and mass leaching varies according to crop type and command area. Canal NO3 concentration and rates of autotrophic denitrification, nitrification, and humus decomposition also dominate or partially dominate in other locations. Each factor, with the exception of O2 reduction rate, is the dominating influence on NO3 groundwater concentration at one or more locations within the study area. Results can be used to determine critical processes and key management actions for future data collection and remediation strategies, with efforts able to be focused on localized areas.

  19. Identifying the Factors Causing Delayed Presentation of Cancer Patients to a Government Medical College of Central India

    PubMed Central

    Yogi, Veenita; Ghori, Hameed Uzzafar; Singh, Om Prakash; Peepre, Karan; Yadav, Suresh; Mohare, Chaitlal

    2015-01-01

    Background The incidence of cancer is increasing throughout the world. One of the prime aims of its management is early diagnosis and therapeutic intervention. Factors causing delay to either of these goals should be identified and rectified. Aim To identify the factors causing delayed initial diagnosis and subsequent management in patients presenting to the Oncology department. Materials and Methods Three hundred proven cancer patients were prospectively evaluated for the pattern of presentation to the outpatient Department of Radiation Oncology of a Government Medical College (MC) in Central India. Results The mean age of presentation was 51.05 years (range 7 months-77 years). The number of male patients was 168 while females were 132. The duration of symptoms ranged from 20 days to 3 years. The number of patients with little/no education presented mainly in advanced stages as compared to their educated counterpart and this difference was statistically significant (p<0.001). The number of patients presenting directly to the department was 108, those diagnosed outside and referred to us was 84 while those diagnosed and received some form of oncologic treatment outside and referred thereafter was 108. The difference in the primary delay between patients presenting directly to the MC versus those diagnosed outside was significant (p=0.0126). The mean duration of starting definitive treatment after presentation to the outpatient was 4.68 days (range 0-22 days) and was very significantly (p< 0.001) less than the secondary delays caused to the other two subsets of patients. Conclusion Factors causing delayed presentation are both patient and system related. It is imperative to educate the common people regarding the early signs and symptoms of cancer. At the same time, the system needs to overhaul its efficiency to avoid secondary delays that adversely affect the treatment outcome. An upgradation of the existing oncology facilities in the public sector can achieve this

  20. A high-throughput gene knockout procedure for Neurospora reveals functions for multiple transcription factors

    PubMed Central

    Colot, Hildur V.; Park, Gyungsoon; Turner, Gloria E.; Ringelberg, Carol; Crew, Christopher M.; Litvinkova, Liubov; Weiss, Richard L.; Borkovich, Katherine A.; Dunlap, Jay C.

    2006-01-01

    The low rate of homologous recombination exhibited by wild-type strains of filamentous fungi has hindered development of high-throughput gene knockout procedures for this group of organisms. In this study, we describe a method for rapidly creating knockout mutants in which we make use of yeast recombinational cloning, Neurospora mutant strains deficient in nonhomologous end-joining DNA repair, custom-written software tools, and robotics. To illustrate our approach, we have created strains bearing deletions of 103 Neurospora genes encoding transcription factors. Characterization of strains during growth and both asexual and sexual development revealed phenotypes for 43% of the deletion mutants, with more than half of these strains possessing multiple defects. Overall, the methodology, which achieves high-throughput gene disruption at an efficiency >90% in this filamentous fungus, promises to be applicable to other eukaryotic organisms that have a low frequency of homologous recombination. PMID:16801547

  1. Scattering from phase-separated vesicles. I. An analytical form factor for multiple static domains

    SciTech Connect

    Heberle, Frederick A.; Anghel, Vinicius N. P.; Katsaras, John

    2015-08-18

    This is the first in a series of studies considering elastic scattering from laterally heterogeneous lipid vesicles containing multiple domains. Unique among biophysical tools, small-angle neutron scattering can in principle give detailed information about the size, shape and spatial arrangement of domains. A general theory for scattering from laterally heterogeneous vesicles is presented, and the analytical form factor for static domains with arbitrary spatial configuration is derived, including a simplification for uniformly sized round domains. The validity of the model, including series truncation effects, is assessed by comparison with simulated data obtained from a Monte Carlo method. Several aspects of the analytical solution for scattering intensity are discussed in the context of small-angle neutron scattering data, including the effect of varying domain size and number, as well as solvent contrast. Finally, the analysis indicates that effects of domain formation are most pronounced when the vesicle's average scattering length density matches that of the surrounding solvent.

  2. Relation of osteoclast activating factor production to extent of bone disease in multiple myeloma.

    PubMed

    Durie, B G; Salmon, S E; Mundy, G R

    1981-01-01

    Measurements of total body myeloma cell number and osteoclast activating factor (OAF) production by bone marrow myeloma cells in vitro were made in 33 patients with plasma cell myeloma. There was a highly significant correlation (P < 0.001) between the amount of OAF produced by bone marrow myeloma cells and the extent of skeletal destruction. Serial studies indicated reduction of OAF production with remission induction and high OAF production at the time of relapse with new bone destruction. Although hypercalcaemia occurred only in patients with the most extensive bone lesions, there was no direct relationship between OAF production and the serum calcium concentration. These data suggest that measurement of OAF production in multiple myeloma may predict those patients at risk for development of extensive skeletal destruction due to this neoplasm.

  3. Factors That Moderate Activity Limitation and Participation Restriction in People With Multiple Sclerosis.

    PubMed

    Goverover, Yael; Strober, Lauren; Chiaravalloti, Nancy; DeLuca, John

    2015-01-01

    We examined the variables most associated with activity limitation (i.e., cooking) and participation restriction (i.e., employment) in 72 people with multiple sclerosis (MS). Participants underwent a comprehensive neuropsychological test battery assessing memory, executive functions, visual perception, and processing speed and completed questionnaires assessing activity, participation, fatigue, and affective symptoms. Results showed that processing speed was the only variable consistently significantly related to both activity and participation. When examining specific aspects of activity and participation in isolation, employment status was significantly associated with education level, visual memory, fatigue, and processing speed. Cooking ability was associated with performance on tasks of working memory, verbal memory, and processing speed. These findings suggest that processing speed is a primary cognitive factor in MS influencing quality of both activity and participation in everyday life. PMID:26122682

  4. Accelerated multiplicative updates and hierarchical ALS algorithms for nonnegative matrix factorization.

    PubMed

    Gillis, Nicolas; Glineur, François

    2012-04-01

    Nonnegative matrix factorization (NMF) is a data analysis technique used in a great variety of applications such as text mining, image processing, hyperspectral data analysis, computational biology, and clustering. In this letter, we consider two well-known algorithms designed to solve NMF problems: the multiplicative updates of Lee and Seung and the hierarchical alternating least squares of Cichocki et al. We propose a simple way to significantly accelerate these schemes, based on a careful analysis of the computational cost needed at each iteration, while preserving their convergence properties. This acceleration technique can also be applied to other algorithms, which we illustrate on the projected gradient method of Lin. The efficiency of the accelerated algorithms is empirically demonstrated on image and text data sets and compares favorably with a state-of-the-art alternating nonnegative least squares algorithm. PMID:22168561

  5. Steroidogenic factor 1 plays multiple roles in endocrine development and function.

    PubMed

    Wong, M; Ikeda, Y; Luo, X; Caron, K M; Weber, T J; Swain, A; Schimmer, B P; Parker, K L

    1997-01-01

    The nuclear hormone receptor family comprises a group of structurally related transcriptional regulators that mediate the actions of diverse ligands, including steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor family also contains members for which activating ligands have not been identified-the orphan nuclear receptors. One of these orphan nuclear receptors, steroidogenic factor 1 (SF-1), has emerged as an essential regulator of steroidogenic cell function within the adrenal cortex and gonads; SF-1 also plays important roles in reproduction at all three levels of the hypothalamic-pituitary-gonadal axis. First identified as a tissue-specific regulator of the transcription of the cytochrome P450 steroid hydroxylases, considerably broader roles for SF-1 were revealed by genetic studies in mice lacking SF-1 due to targeted gene disruption. These SF-1-knockout mice had agenesis of their adrenal glands and gonads, male-to-female sex reversal of their internal and external genitalia, impaired gonadotrope function, and agenesis of the ventromedial hypothalamic nucleus. These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels. Despite these insights into roles of SF-1, the precise mechanisms by which SF-1 exerts its multiple effects remain to be determined. This review highlights experiments that have established SF-1 as a pivotal determinant of endocrine differentiation and function and identifies areas in which additional studies are needed to expand our understanding of SF-1 action.

  6. Statistical mechanical model of coupled transcription from multiple promoters due to transcription factor titration.

    PubMed

    Rydenfelt, Mattias; Cox, Robert Sidney; Garcia, Hernan; Phillips, Rob

    2014-01-01

    Transcription factors (TFs) with regulatory action at multiple promoter targets is the rule rather than the exception, with examples ranging from the cAMP receptor protein (CRP) in E. coli that regulates hundreds of different genes simultaneously to situations involving multiple copies of the same gene, such as plasmids, retrotransposons, or highly replicated viral DNA. When the number of TFs heavily exceeds the number of binding sites, TF binding to each promoter can be regarded as independent. However, when the number of TF molecules is comparable to the number of binding sites, TF titration will result in correlation ("promoter entanglement") between transcription of different genes. We develop a statistical mechanical model which takes the TF titration effect into account and use it to predict both the level of gene expression for a general set of promoters and the resulting correlation in transcription rates of different genes. Our results show that the TF titration effect could be important for understanding gene expression in many regulatory settings.

  7. Statistical mechanical model of coupled transcription from multiple promoters due to transcription factor titration

    NASA Astrophysics Data System (ADS)

    Rydenfelt, Mattias; Cox, Robert Sidney, III; Garcia, Hernan; Phillips, Rob

    2014-01-01

    Transcription factors (TFs) with regulatory action at multiple promoter targets is the rule rather than the exception, with examples ranging from the cAMP receptor protein (CRP) in E. coli that regulates hundreds of different genes simultaneously to situations involving multiple copies of the same gene, such as plasmids, retrotransposons, or highly replicated viral DNA. When the number of TFs heavily exceeds the number of binding sites, TF binding to each promoter can be regarded as independent. However, when the number of TF molecules is comparable to the number of binding sites, TF titration will result in correlation (“promoter entanglement”) between transcription of different genes. We develop a statistical mechanical model which takes the TF titration effect into account and use it to predict both the level of gene expression for a general set of promoters and the resulting correlation in transcription rates of different genes. Our results show that the TF titration effect could be important for understanding gene expression in many regulatory settings.

  8. [Factors associated to the work situation of patients with multiple sclerosis].

    PubMed

    Cores, Evangelina V; Vanotti, Sandra; Burin, Débora I; Politis, Daniel G; Villa, Andrés

    2014-02-16

    Introduccion. La esclerosis multiple es una enfermedad neurologica desmielinizante que suele provocar trastornos motrices, perceptivos, afectivos y cognitivos a quienes la padecen. Estos sintomas pueden llevar a la persona a perder su empleo, y disminuir la calidad de vida del paciente y sus familiares. Objetivo. Revisar estudios sobre variables demograficas, clinicas, cognitivas, psiquiatricas, laborales y sociales asociadas con la situacion laboral. Desarrollo. Estudios transversales y longitudinales han detectado variables relacionadas con el desempleo. Las investigaciones empiricas muestran una influencia clara de la discapacidad fisica, la fatiga y el curso de la enfermedad sobre la situacion laboral. Sin embargo, el genero, la depresion, la edad, la duracion de la enfermedad y las variables cognitivas no poseen el mismo grado de evidencia. Caracteristicas de la ocupacion, como discriminacion laboral, actitud del empleador, leyes laborales, actitud de los compañeros de trabajo y dificultades en el transporte han sido variables poco consideradas. Conclusiones. Muchos de los factores que determinan la perdida de empleo en un paciente con esclerosis multiple pueden identificarse a tiempo para poder modificarlos o compensarlos. Los conocimientos aportados por los estudios reseñados permiten detectar a aquellos pacientes que se encuentran en riesgo de perder su empleo para realizar intervenciones posibles con el objetivo de prevenir esta situacion. En particular, el perfil de vulnerabilidad incluye alta discapacidad fisica y fatiga, curso progresivo de la enfermedad y presencia de deterioro cognitivo, entre otros.

  9. Colony-stimulating Factor-1 Receptor Utilizes Multiple Signaling Pathways to Induce Cyclin D2 Expression

    PubMed Central

    Dey, Arunangsu; She, Hongyun; Kim, Leopold; Boruch, Allan; Guris, Deborah L.; Carlberg, Kristen; Sebti, Saïd M.; Woodley, David T.; Imamoto, Akira; Li, Wei

    2000-01-01

    Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos and delayed early genes such as D-type cyclins (D1 and D2), whose products play essential roles in the G1 to S phase transition of the cell cycle. Little is known, however, about the cytoplasmic signal transduction pathways that connect the surface CSF-1 receptor to these genes in the nucleus. We have investigated the signaling mechanism of CSF-1-induced D2 expression. Analyses of CSF-1 receptor autophosphorylation mutants show that, although certain individual mutation has a partial inhibitory effect, only multiple combined mutations completely block induction of D2 in response to CSF-1. We report that at least three parallel pathways, the Src pathway, the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and the c-myc pathway, are involved. Induction of D2 is partially inhibited in Src−/− bone marrow-derived macrophages and by Src inhibitor PP1 and is enhanced in v-Src-overexpressing cells. Activation of myc's transactivating activity selectively induces D2 but not D1. Blockade of c-myc expression partially blocks CSF-1-induced D2 expression. Complete inhibition of the MEK/ERK pathway causes 50% decrease of D2 expression. Finally, simultaneous inhibition of Src, MEK activation, and c-myc expression additively blocks CSF-1-induced D2 expression. This study indicates that multiple signaling pathways are involved in full induction of a single gene, and this finding may also apply broadly to other growth factor-inducible genes. PMID:11071910

  10. Risk factors of multiple system atrophy: a case-control study in French patients.

    PubMed

    Vidal, Jean-Sébastien; Vidailhet, Marie; Elbaz, Alexis; Derkinderen, Pascal; Tzourio, Christophe; Alpérovitch, Annick

    2008-04-30

    Multiple system atrophy (MSA) is a rare sporadic progressive neurodegenerative disorder. MSA risk factors are poorly known. The objectives of this case-control study were to study environmental risk factors associated with MSA. Cases were recruited through five French referral centers. Controls matched for age, gender, and living area were recruited from healthy relatives of inpatients free of any parkinsonian syndrome of the same centers. Subjects were interviewed about exposure to environmental factors (pesticides, solvents, etc.), occupation and food habits, and use of anti-inflammatory drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using conditional logistic regression. Seventy-one cases and 71 matched controls were included. Low education level was more frequent in cases than in controls. Controls drank more alcohol than did cases (OR = 0.5 [0.2-1.1]) and the risk of MSA decreased with increasing alcohol consumption (P = 0.04). Controls ate fish and sea food more often and drank more tea than cases. Aspirin intake was more frequent among controls than did cases (OR = 0.5 [0.2-1.0]) and the risk of MSA decreased with the frequency of intake (P = 0.0002). MSA was not associated to exposure to pesticides, solvents, and other toxics neither to occupations, except plant and machine operators and assemblers (OR = 10.0 [2.1-47.5]) where the risk of MSA increased with number of years in this occupation (P = 0.004). This case-control study provided new findings about risk factors of MSA. On another hand, it did not confirm the previously reported association between MSA and exposure to pesticides.

  11. Factor Configurations with Governance as Conditions for Low HIV/AIDS Prevalence in HIV/AIDS Recipient Countries: Fuzzy-set Analysis.

    PubMed

    Lee, Hwa-Young; Yang, Bong-Min; Kang, Minah

    2015-11-01

    This paper aims to investigate whether good governance of a recipient country is a necessary condition and what combinations of factors including governance factor are sufficient for low prevalence of HIV/AIDS in HIV/AIDS aid recipient countries during the period of 2002-2010. For this, Fuzzy-set Qualitative Comparative Analysis (QCA) was used. Nine potential attributes for a causal configuration for low HIV/AIDS prevalence were identified through a review of previous studies. For each factor, full membership, full non-membership, and crossover point were specified using both author's knowledge and statistical information of the variables. Calibration and conversion to a fuzzy-set score were conducted using Fs/QCA 2.0 and probabilistic tests for necessary and sufficiency were performed by STATA 11. The result suggested that governance is the necessary condition for low prevalence of HIV/AIDS in a recipient country. From sufficiency test, two pathways were resulted. The low level of governance can lead to low level of HIV/AIDS prevalence when it is combined with other favorable factors, especially, low economic inequality, high economic development and high health expenditure. However, strengthening governance is a more practical measure to keep low prevalence of HIV/AIDS because it is hard to achieve both economic development and economic quality. This study highlights that a comprehensive policy measure is the key for achieving low prevalence of HIV/AIDS in recipient country. PMID:26617451

  12. Factor Configurations with Governance as Conditions for Low HIV/AIDS Prevalence in HIV/AIDS Recipient Countries: Fuzzy-set Analysis.

    PubMed

    Lee, Hwa-Young; Yang, Bong-Min; Kang, Minah

    2015-11-01

    This paper aims to investigate whether good governance of a recipient country is a necessary condition and what combinations of factors including governance factor are sufficient for low prevalence of HIV/AIDS in HIV/AIDS aid recipient countries during the period of 2002-2010. For this, Fuzzy-set Qualitative Comparative Analysis (QCA) was used. Nine potential attributes for a causal configuration for low HIV/AIDS prevalence were identified through a review of previous studies. For each factor, full membership, full non-membership, and crossover point were specified using both author's knowledge and statistical information of the variables. Calibration and conversion to a fuzzy-set score were conducted using Fs/QCA 2.0 and probabilistic tests for necessary and sufficiency were performed by STATA 11. The result suggested that governance is the necessary condition for low prevalence of HIV/AIDS in a recipient country. From sufficiency test, two pathways were resulted. The low level of governance can lead to low level of HIV/AIDS prevalence when it is combined with other favorable factors, especially, low economic inequality, high economic development and high health expenditure. However, strengthening governance is a more practical measure to keep low prevalence of HIV/AIDS because it is hard to achieve both economic development and economic quality. This study highlights that a comprehensive policy measure is the key for achieving low prevalence of HIV/AIDS in recipient country.

  13. Factor Configurations with Governance as Conditions for Low HIV/AIDS Prevalence in HIV/AIDS Recipient Countries: Fuzzy-set Analysis

    PubMed Central

    Lee, Hwa-Young; Kang, Minah

    2015-01-01

    This paper aims to investigate whether good governance of a recipient country is a necessary condition and what combinations of factors including governance factor are sufficient for low prevalence of HIV/AIDS in HIV/AIDS aid recipient countries during the period of 2002-2010. For this, Fuzzy-set Qualitative Comparative Analysis (QCA) was used. Nine potential attributes for a causal configuration for low HIV/AIDS prevalence were identified through a review of previous studies. For each factor, full membership, full non-membership, and crossover point were specified using both author's knowledge and statistical information of the variables. Calibration and conversion to a fuzzy-set score were conducted using Fs/QCA 2.0 and probabilistic tests for necessary and sufficiency were performed by STATA 11. The result suggested that governance is the necessary condition for low prevalence of HIV/AIDS in a recipient country. From sufficiency test, two pathways were resulted. The low level of governance can lead to low level of HIV/AIDS prevalence when it is combined with other favorable factors, especially, low economic inequality, high economic development and high health expenditure. However, strengthening governance is a more practical measure to keep low prevalence of HIV/AIDS because it is hard to achieve both economic development and economic quality. This study highlights that a comprehensive policy measure is the key for achieving low prevalence of HIV/AIDS in recipient country. PMID:26617451

  14. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1

    PubMed Central

    Wang, XingChun; Liu, Huan; Chen, Jiaqi; Li, Yan; Qu, Shen

    2015-01-01

    The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels. PMID:26366173

  15. Concomitant Factors Leading to an Atypical Osteonecrosis of the Jaw in a Patient with Multiple Myeloma

    PubMed Central

    Miranda-Rius, Jaume; Brunet-Llobet, Lluís; Lahor-Soler, Eduard; Giménez-Rubio, Josep Anton

    2014-01-01

    Osteonecrosis of the jaw (ONJ) is a site specific osseous pathology, characterized by chronic exposed bone in the mouth, which needs to be reinforced periodically within the medical literature. ONJ is a clinical entity with many possible aetiologies and its pathogenesis is not well understood. The risk factors for ONJ include bisphosphonates treatments, head and neck radiotherapy, dental procedures involving bone surgery, and trauma. Management of ONJ has centred on efforts to eliminate or reduce severity of symptoms, to slow or prevent the progression of disease, and to eradicate diseased bone. This case describes a rare case of ONJ in a 64-year-old Caucasian male diagnosed with multiple myeloma stage III. The lesion was related to a traumatic injury during mastication. Eighteen months ago in the same area the molar 37 was extracted, achieving a complete satisfactory healing, when only 2 doses of zoledronic acid had been administered. Actinomyces bacterial aggregates were also identified in the microscopic analysis. The management of this osteonecrotic lesion included antibiotic treatment and chlorhexidine topical gel administration. The evolution was monitored every two weeks until patient's death. The authors provide a discussion of the etiology, pathogenesis, diagnosis, and management. This case report may shed light on the controversies about concomitant factors and mechanisms inducing ONJ. PMID:25140178

  16. Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis

    PubMed Central

    de Melo, Jimmy; Clark, Brian S.; Blackshaw, Seth

    2016-01-01

    Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27Kip1 in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2. PMID:27605455

  17. Risk factors for multiple sclerosis and associations with anti-EBV antibody titers.

    PubMed

    Mouhieddine, Tarek H; Darwish, Hala; Fawaz, Lama; Yamout, Bassem; Tamim, Hani; Khoury, Samia J

    2015-05-01

    Multiple sclerosis (MS) is an inflammatory demyelination of the central nervous system. We investigated the prevalence of EBV seropositivity and other known risk factors for MS (age, smoking, low vitamin D) and their effect on anti-EBV antibody titers. We retrospectively studied 249 MS patients receiving care at the American University of Beirut Medical Center and 230 controls, during 2010-2014. EBV seropositivity was higher in MS patients compared to controls for both anti-VCA (99.5%; 97.2%) and anti-EBNA-1 (96.3%; 89.4%), and the titers were significantly higher in MS patients. MS patients had a significantly lower vitamin D level (15.5 ± 8.3 ng/ml) compared to controls (20.4 ± 11.3 ng/ml). The proportion of heavy smokers and overweight individuals was significantly higher in MS patients. Lebanese MS patients have risk factors similar to those in western countries. Older age and female gender were associated with a higher anti-VCA titer and male gender with a higher anti-EBNA-1.

  18. Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis

    NASA Astrophysics Data System (ADS)

    de Melo, Jimmy; Clark, Brian S.; Blackshaw, Seth

    2016-09-01

    Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27Kip1 in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2.

  19. Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis.

    PubMed

    de Melo, Jimmy; Clark, Brian S; Blackshaw, Seth

    2016-01-01

    Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27(Kip1) in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2. PMID:27605455

  20. A factor analysis-multiple regression model for source apportionment of suspended particulate matter

    NASA Astrophysics Data System (ADS)

    Okamoto, Shin'ichi; Hayashi, Masayuki; Nakajima, Masaomi; Kainuma, Yasutaka; Shiozawa, Kiyoshige

    A factor analysis-multiple regression (FA-MR) model has been used for a source apportionment study in the Tokyo metropolitan area. By a varimax rotated factor analysis, five source types could be identified: refuse incineration, soil and automobile, secondary particles, sea salt and steel mill. Quantitative estimations using the FA-MR model corresponded to the calculated contributing concentrations determined by using a weighted least-squares CMB model. However, the source type of refuse incineration identified by the FA-MR model was similar to that of biomass burning, rather than that produced by an incineration plant. The estimated contributions of sea salt and steel mill by the FA-MR model contained those of other sources, which have the same temporal variation of contributing concentrations. This symptom was caused by a multicollinearity problem. Although this result shows the limitation of the multivariate receptor model, it gives useful information concerning source types and their distribution by comparing with the results of the CMB model. In the Tokyo metropolitan area, the contributions from soil (including road dust), automobile, secondary particles and refuse incineration (biomass burning) were larger than industrial contributions: fuel oil combustion and steel mill. However, since vanadium is highly correlated with SO 42- and other secondary particle related elements, a major portion of secondary particles is considered to be related to fuel oil combustion.

  1. Multiple neuroendocrine responses to chronic social stress: interaction between individual characteristics and situational factors.

    PubMed

    Mormède, P; Lemaire, V; Castanon, N; Dulluc, J; Laval, M; Le Moal, M

    1990-06-01

    After four weeks of individual housing, male Wistar rats (selected for high or low spontaneous aggressiveness by multiple round-robin encounters) were housed three per cage and submitted to four weeks of chronic social stress consisting of changing membership in the social groups by daily rotation of the animals among cages every day according to a random permutation procedure. In addition, half the males in each condition were housed with three females. Each environmental condition triggered different neuroendocrine changes. Cohabitation with females increased the hypothalamo-pituitary-adrenocortical axis activity, including enlargement of adrenals and increased circulating corticosterone levels. On the other hand, daily rotation of the rats between different social groups activated part of the sympathetic nervous system, such as increased phenylethanolamine N-methyl transferase (PNMT) activity in the adrenals. The level of aggressiveness, however, had no direct influence but interacted with environmental factors on such neuroendocrine measures as circulating testosterone or plasma renin activity. These results indicate that during chronic stress, there is no single, unique response by the animal, but a highly complex set of neuroendocrine changes, dependent on the interaction between individual characteristics (the level of aggressiveness is an example) and situational factors. PMID:1975698

  2. Effect of multiple clinical factors on recurrent angina after percutaneous coronary intervention

    PubMed Central

    Zhang, Jing; Liu, Chengyu; Pan, Chenliang; Bai, Ming; Zhang, Jin; Peng, Yu; Zheng, Dingchang; Zhang, Zheng

    2016-01-01

    Abstract Recurrent angina (RA) has an important influence on health status of patients after percutaneous coronary intervention (PCI). This study aimed to retrospectively investigate the effect of multiple clinical factors on both short-term and long-term development of RA. A total of 398 ST-segment elevation myocardial infarction (STEMI) patients were studied for up to 12 months. The primary clinical outcome, RA, was assessed at 1-month and 12-month. In multivariate analyses, the effect of clinical factors, including baseline demographics, medical history, infarction-related arteries, procedural characteristics of PCI, and the use of medicines, was investigated in patients with and without RA. The Logistic regression analysis showed that the patients with treatment through radial approach PCI (odds ratio [OR]: 0.42, 95% confidence interval [CI]: 0.18–0.96, P < 0.05) were less likely to have RA during 1-month assessment. During 12 months after PCI, male patients (OR: 0.53, 95% CI: 0.29–0.96, P < 0.05), and/or those treated with radial approach PCI (OR: 0.45, 95% CI: 0.21–0.97, P < 0.05) were less likely to have RA, whereas the patients with infarction related artery (IRA) in left anterior descending (LAD) (OR: 2.41, 95% CI: 1.20–4.84, P < 0.01) were more likely to have RA at follow-up. The Cox regression analysis further revealed that the patients with infarction of the LAD artery (hazard ratio [HR]: 2.08, 95% CI: 1.10–3.92, P < 0.05), but not with treatment through radial artery during PCI (HR: 0.42, 95% CI: 0.18–0.96, P < 0.05) had higher potential of development of RA during 12 months after PCI. We studied the effects of multiple clinical factors on the development of RA after PCI. Our findings suggest that patients with infarction of the LAD artery, and/or treatment not through radial artery during PCI were associated with higher risk of RA and may require close follow-up. PMID:27741110

  3. Possible environmental factors underlying amphibian decline in eastern Puerto Rico: Analysis of U.S. government data archives

    USGS Publications Warehouse

    Stallard, R.F.

    2001-01-01

    The past three decades have seen major declines in populations of several species of amphibians at high elevations in eastern Puerto Rico, a region unique in the humid tropics because of the degree of environmental monitoring that has taken place through the efforts of U.S. government agencies. I examined changes in environmental conditions by examining time-series data sets that extend back at least into the 1980s, a period when frog populations were declining. The data include forest cover; annual mean, minimum, and maximum daily temperature; annual rainfall; rain and stream chemistry; and atmospheric-dust transport. I examined satellite imagery and air-chemistry samples from a single National Aeronautics and Space Administration aircraft flight across the Caribbean showing patches of pollutants, described as thin sheets or lenses, in the lower troposphere. The main source of these pollutants appeared to be fires from land clearing and deforestation, primarily in Africa. Some pollutant concentrations were high and, in the case of ozone, approached health limits set for urban air. Urban pollution impinging on Puerto Rico, dust generation from Africa (potential soil pathogens), and tropical forest burning (gaseous pollutants) have all increased during the last three decades, overlapping the timing of amphibian declines in eastern Puerto Rico. None of the data sets pointed directly to changes so extreme that they might be considered a direct lethal cause of amphibian declines in Puerto Rico. More experimental research is required to link any of these environmental factors to this problem.

  4. A Common Biosynthetic Pathway Governs the Dimerization and Secretion of Inhibin and Related Transforming Growth Factor β (TGFβ) Ligands*

    PubMed Central

    Walton, Kelly L.; Makanji, Yogeshwar; Wilce, Matthew C.; Chan, Karen L.; Robertson, David M.; Harrison, Craig A.

    2009-01-01

    The assembly and secretion of transforming growth factor β superfamily ligands is dependent upon non-covalent interactions between their pro- and mature domains. Despite the importance of this interaction, little is known regarding the underlying regulatory mechanisms. In this study, the binding interface between the pro- and mature domains of the inhibin α-subunit was characterized using in vitro mutagenesis. Three hydrophobic residues near the N terminus of the prodomain (Leu30, Phe37, Leu41) were identified that, when mutated to alanine, disrupted heterodimer assembly and secretion. It is postulated that these residues mediate dimerization by interacting non-covalently with hydrophobic residues (Phe271, Ile280, Pro283, Leu338, and Val340) on the outer convex surface of the mature α-subunit. Homology modeling indicated that these mature residues are located at the interface between two β-sheets of the α-subunit and that their side chains form a hydrophobic packing core. Mutation of these residues likely disturbs the conformation of this region, thereby disrupting non-covalent interactions with the prodomain. A similar hydrophobic interface was identified spanning the pro- and mature domains of the inhibin βA-subunit. Mutation of key residues, including Ile62, Leu66, Phe329, and Pro341, across this interface was disruptive for the production of both inhibin A and activin A. In addition, mutation of Ile62 and Leu66 in the βA-propeptide reduced its ability to bind, or inhibit the activity of, activin A. Conservation of the identified hydrophobic motifs in the pro- and mature domains of other transforming growth factor β superfamily ligands suggests that we have identified a common biosynthetic pathway governing dimer assembly. PMID:19193648

  5. An examination of the factors governing the development of karst topography in the Cumberland Valley of Pennsylvania

    SciTech Connect

    Ackerman, R.V. . Dept. of Geological Sciences)

    1993-03-01

    The landscape of the Cumberland Valley of South Central Pennsylvania is dominated by karst topography. A study was initiated to determine if the development of karst was controlled primarily by geologic structure or by lithologic differences. Existing data concerning the geographic locations of karst features, the hydrogeologic characteristics of the Cumberland Valley, and the chemistry of the eleven carbonate formations within the 518 km[sup 2] study area were compiled. Data concerning 366 mapped sinkholes and over 9,000 additional karst features and their relations to the structural, lithological and spatial characteristics of the study area were collected and compiled into the database. Other factors contributing to karst development such as groundwater flow, soil and colluvium characteristics, and geographic distribution were considered. The data suggest that structure dominates lithology in the development of karst features within the study area. Structural features such as fractures, joints and folds, which create secondary porosity, are prerequisite for solution of the carbonate bedrock. Joint systems, fold axes, igneous intrusions, caves, springs and groundwater flow have a significant impact on the development of karst features. The presence of faults proved inconclusive. There are a greater number of karst features per unit area in areas of purer limestones (units with a lower percentage of acid insoluble residue). Lithological variations impact karst development only when structural features are present to provide secondary porosity that enhances chemical weathering. The distribution of karst features and the geologic factors governing their development and distribution should be taken into account when land-use decisions in karst terrains are made.

  6. Apoglobin Stability Is the Major Factor Governing both Cell-free and in Vivo Expression of Holomyoglobin*♦

    PubMed Central

    Samuel, Premila P.; Smith, Lucian P.; Phillips, George N.; Olson, John S.

    2015-01-01

    Expression levels in animal muscle tissues and in Escherichia coli vary widely for naturally occurring mammalian myoglobins (Mb). To explore this variation, we developed an in vitro transcription and wheat germ extract-based translation assay to examine quantitatively the factors that govern expression of holoMb. We constructed a library of naturally occurring Mbs from two terrestrial and four deep-diving aquatic mammals and three distal histidine mutants designed to enhance apoglobin stability but decrease hemin affinity. A strong linear correlation is observed between cell-free expression levels of holo-metMb variants and their corresponding apoglobin stabilities, which were measured independently by guanidine HCl-induced unfolding titrations using purified proteins. In contrast, there is little dependence of expression on hemin affinity. Our results confirm quantitatively that deep diving mammals have highly stable Mbs that express to higher levels in animal myocytes, E. coli, and the wheat germ cell-free system than Mbs from terrestrial mammals. Our theoretical analyses show that the rate of aggregation of unfolded apoMb is very large, and as a result, the key factor for high level expression of holoMb, and presumably other heme proteins, is an ultra high fraction of folded, native apoglobin that is capable of rapidly binding hemin. This fraction is determined by the overall equilibrium folding constant and not hemin affinity. These results also demonstrate that the cell-free transcription/translation system can be used as a high throughput platform to screen for apoglobin stability without the need to generate large amounts of protein for in vitro unfolding measurements. PMID:26205820

  7. Multiple factors affect a population of Agassiz's desert tortoise (Gopherus agassizii) in the Northwestern Mojave Desert

    USGS Publications Warehouse

    Berry, Kristin H.; Yee, Julie L.; Coble, Ashley A.; Perry, William M.; Shields, Timothy A.

    2013-01-01

    Numerous factors have contributed to declines in populations of the federally threatened Agassiz's Desert Tortoise (Gopherus agassizii) and continue to limit recovery. In 2010, we surveyed a low-density population on a military test facility in the northwestern Mojave Desert of California, USA, to evaluate population status and identify potential factors contributing to distribution and low densities. Estimated densities of live tortoises ranged spatially from 1.2/km2 to 15.1/km2. Although only one death of a breeding-age tortoise was recorded for the 4-yr period prior to the survey, remains of 16 juvenile and immature tortoises were found, and most showed signs of predation by Common Ravens (Corvus corax) and mammals. Predation may have limited recruitment of young tortoises into the adult size classes. To evaluate the relative importance of different types of impacts to tortoises, we developed predictive models for spatially explicit densities of tortoise sign and live tortoises using topography (i.e., slope), predators (Common Raven, signs of mammalian predators), and anthropogenic impacts (distances from paved road and denuded areas, density of ordnance fragments) as covariates. Models suggest that densities of tortoise sign increased with slope and signs of mammalian predators and decreased with Common Ravens, while also varying based on interaction effects involving these predictors as well as distances from paved roads, denuded areas, and ordnance. Similarly, densities of live tortoises varied by interaction effects among distances to denuded areas and paved roads, density of ordnance fragments, and slope. Thus multiple factors predict the densities and distribution of this population.

  8. Ethylene Response Factors Are Controlled by Multiple Harvesting Stresses in Hevea brasiliensis

    PubMed Central

    Putranto, Riza-Arief; Duan, Cuifang; Kuswanhadi; Chaidamsari, Tetty; Rio, Maryannick; Piyatrakul, Piyanuch; Herlinawati, Eva; Pirrello, Julien; Dessailly, Florence; Leclercq, Julie; Bonnot, François; Tang, Chaorong; Hu, Songnian; Montoro, Pascal

    2015-01-01

    Tolerance of recurrent mechanical wounding and exogenous ethylene is a feature of the rubber tree. Latex harvesting involves tapping of the tree bark and ethephon is applied to increase latex flow. Ethylene is an essential element in controlling latex production. The ethylene signalling pathway leads to the activation of Ethylene Response Factor (ERF) transcription factors. This family has been identified in Hevea brasiliensis. This study set out to understand the regulation of ERF genes during latex harvesting in relation to abiotic stress and hormonal treatments. Analyses of the relative transcript abundance were carried out for 35 HbERF genes in latex, in bark from mature trees and in leaves from juvenile plants under multiple abiotic stresses. Twenty-one HbERF genes were regulated by harvesting stress in laticifers, revealing an overrepresentation of genes in group IX. Transcripts of three HbERF-IX genes from HbERF-IXc4, HbERF-IXc5 and HbERF-IXc6 were dramatically accumulated by combining wounding, methyl jasmonate and ethylene treatments. When an ethylene inhibitor was used, the transcript accumulation for these three genes was halted, showing ethylene-dependent induction. Subcellular localization and transactivation experiments confirmed that several members of HbERF-IX are activator-type transcription factors. This study suggested that latex harvesting induces mechanisms developed for the response to abiotic stress. These mechanisms probably depend on various hormonal signalling pathways. Several members of HbERF-IX could be essential integrators of complex hormonal signalling pathways in Hevea. PMID:25906196

  9. Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

    PubMed Central

    Soto-De Leon, Sara; Camargo, Milena; Sanchez, Ricardo; Munoz, Marina; Perez-Prados, Antonio; Purroy, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2011-01-01

    Background Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity. Conclusions According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies. PMID:21379574

  10. Ethylene Response Factors Are Controlled by Multiple Harvesting Stresses in Hevea brasiliensis.

    PubMed

    Putranto, Riza-Arief; Duan, Cuifang; Kuswanhadi; Chaidamsari, Tetty; Rio, Maryannick; Piyatrakul, Piyanuch; Herlinawati, Eva; Pirrello, Julien; Dessailly, Florence; Leclercq, Julie; Bonnot, François; Tang, Chaorong; Hu, Songnian; Montoro, Pascal

    2015-01-01

    Tolerance of recurrent mechanical wounding and exogenous ethylene is a feature of the rubber tree. Latex harvesting involves tapping of the tree bark and ethephon is applied to increase latex flow. Ethylene is an essential element in controlling latex production. The ethylene signalling pathway leads to the activation of Ethylene Response Factor (ERF) transcription factors. This family has been identified in Hevea brasiliensis. This study set out to understand the regulation of ERF genes during latex harvesting in relation to abiotic stress and hormonal treatments. Analyses of the relative transcript abundance were carried out for 35 HbERF genes in latex, in bark from mature trees and in leaves from juvenile plants under multiple abiotic stresses. Twenty-one HbERF genes were regulated by harvesting stress in laticifers, revealing an overrepresentation of genes in group IX. Transcripts of three HbERF-IX genes from HbERF-IXc4, HbERF-IXc5 and HbERF-IXc6 were dramatically accumulated by combining wounding, methyl jasmonate and ethylene treatments. When an ethylene inhibitor was used, the transcript accumulation for these three genes was halted, showing ethylene-dependent induction. Subcellular localization and transactivation experiments confirmed that several members of HbERF-IX are activator-type transcription factors. This study suggested that latex harvesting induces mechanisms developed for the response to abiotic stress. These mechanisms probably depend on various hormonal signalling pathways. Several members of HbERF-IX could be essential integrators of complex hormonal signalling pathways in Hevea.

  11. Near-field-assisted localization: effect of size and filling factor of randomly distributed zinc oxide nanoneedles on multiple scattering and localization of light

    NASA Astrophysics Data System (ADS)

    Silies, Martin; Mascheck, Manfred; Leipold, David; Kollmann, Heiko; Schmidt, Slawa; Sartor, Janos; Yatsui, Takashi; Kitamura, Kokoro; Ohtsu, Motoicho; Kalt, Heinz; Runge, Erich; Lienau, Christoph

    2016-07-01

    We investigate the influence of the diameter and the filling factor of randomly arranged ZnO nanoneedles on the multiple scattering and localization of light in disordered dielectrics. Coherent, ultra-broadband second-harmonic (SH) microscopy is used to probe the spatial localization of light in representative nm-sized ZnO arrays of needles. We observe strong fluctuations of the SH intensity inside different ZnO needle geometries. Comparison of the SH intensity distributions with predictions based on a one-parameter scaling model indicate that SH fluctuations can be taken as a quantitative measure for the degree of localization. Interestingly, the strongest localization signatures are found for densely packed arrays of thin needles with diameters in the range of only 30 nm range, despite the small scattering cross section of these needles. FDTD simulations indicate that in this case coupling of electric near-fields between neighbouring needles governs the localization.

  12. Factors Contributing to the Accumulation of Primary Teacher's Debts to the Government of Tanzania: A Case Study for Dar Es Salaam Region

    ERIC Educational Resources Information Center

    Kombo, Ibun

    2015-01-01

    This paper presents the findings of the study which was conducted to determine factors contributing to the accumulation of primary school teacher's debts to the Government of Tanzania, a case study of Dar es Salaam Region in its three municipalities namely, Ilala, Kinondoni and Temeke. Data was obtained through sampling method which also helped to…

  13. Investigating the Interpersonal and Contextual Factors Govern Saudi Lecturers' Motivation in Creating Innovative Blended Learning Environment That Web 2.0-Based

    ERIC Educational Resources Information Center

    Alghanmi, Sahar

    2014-01-01

    Sustaining success in higher education within an ever-changing landscape largely depends on academics' motivation to cope with it. Essentially, this study aims to explore the interpersonal and contextual factors that govern the introduction of blended learning in a Saudi context. A collective case study approach was employed with Self-…

  14. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

    PubMed Central

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  15. Multiplication factor for open ground storey buildings-a reliability based evaluation

    NASA Astrophysics Data System (ADS)

    Haran Pragalath, D. C.; Avadhoot, Bhosale; Robin, Davis P.; Pradip, Sarkar

    2016-06-01

    Open Ground Storey (OGS) framed buildings where the ground storey is kept open without infill walls, mainly to facilitate parking, is increasing commonly in urban areas. However, vulnerability of this type of buildings has been exposed in past earthquakes. OGS buildings are conventionally designed by a bare frame analysis that ignores the stiffness of the infill walls present in the upper storeys, but doing so underestimates the inter-storey drift (ISD) and thereby the force demand in the ground storey columns. Therefore, a multiplication factor (MF) is introduced in various international codes to estimate the design forces (bending moments and shear forces) in the ground storey columns. This study focuses on the seismic performance of typical OGS buildings designed by means of MFs. The probabilistic seismic demand models, fragility curves, reliability and cost indices for various frame models including bare frames and fully infilled frames are developed. It is found that the MF scheme suggested by the Israel code is better than other international codes in terms of reliability and cost.

  16. Scattering from phase-separated vesicles. I. An analytical form factor for multiple static domains

    DOE PAGESBeta

    Heberle, Frederick A.; Anghel, Vinicius N. P.; Katsaras, John

    2015-08-18

    This is the first in a series of studies considering elastic scattering from laterally heterogeneous lipid vesicles containing multiple domains. Unique among biophysical tools, small-angle neutron scattering can in principle give detailed information about the size, shape and spatial arrangement of domains. A general theory for scattering from laterally heterogeneous vesicles is presented, and the analytical form factor for static domains with arbitrary spatial configuration is derived, including a simplification for uniformly sized round domains. The validity of the model, including series truncation effects, is assessed by comparison with simulated data obtained from a Monte Carlo method. Several aspects ofmore » the analytical solution for scattering intensity are discussed in the context of small-angle neutron scattering data, including the effect of varying domain size and number, as well as solvent contrast. Finally, the analysis indicates that effects of domain formation are most pronounced when the vesicle's average scattering length density matches that of the surrounding solvent.« less

  17. [Brain-derived and ciliary neurotrophic factors in patients with multiple sclerosis].

    PubMed

    Trushnikova, T N; Medvedeva, E L; Baĭdina, T V; Danilova, M A

    2014-01-01

    Objective. To study serum concentrations of BDNF and CNTF in patients with multiple sclerosis (MS) and compare them to clinical characteristics of MS. Material and methods. We examined 43 patients with confirmed diagnosis of MS according to McDonald's criteria with remitting type of disease course. Patients were in a stable condition and did not receive hormone treatment during the last 30 days. Serum concentrations of BDNF and CNTF were measured using ELISA. Results. Mean serum BDNF concentration was 7.9 (5.21; 14.7) ng/ml that was significantly lower (p=0.0001) compared to control values and was correlated with depression severity (r= -0.31, p=0.04) and physical asthenia (r= -0.32, p=0.04). CNTF concentration was 69.9 (31.2; 123.3) pg/ml (CNTF was not found in healthy people) and was correlated with the results of cognitive function assessment (the PASAT test) (r= -0.30, p=0.046). Conclusion. The difference in BDNF and CNTF serum concentrations between MS patients and healthy people and correlations with some clinical characteristics of MS provide evidence for the involvement of these factors in MS pathogenesis. PMID:25591532

  18. Multiple signaling pathways leading to the activation of interferon regulatory factor 3.

    PubMed

    Servant, Marc J; Grandvaux, Nathalie; Hiscott, John

    2002-09-01

    Virus infection of susceptible cells activates multiple signaling pathways that orchestrate the activation of genes, such as cytokines, involved in the antiviral and innate immune response. Among the kinases induced are the mitogen-activated protein (MAP) kinases, Jun-amino terminal kinases (JNK) and p38, the IkappaB kinase (IKK) and DNA-PK. In addition, virus infection also activates an uncharacterized VAK responsible for the C-terminal phosphorylation and subsequent activation of interferon regulatory factor 3 (IRF-3). Virus-mediated activation of IRF-3 through VAK is dependent on viral entry and transcription, since replication deficient virus failed to induce IRF-3 activity. The pathways leading to VAK activation are not well characterized, but IRF-3 appears to represent a novel cellular detection pathway that recognizes viral nucleocapsid (N) structure. Recently, the range of inducers responsible for IRF-3 activation has increased. In addition to virus infection, recognition of bacterial infection mediated through lipopolysaccharide by Toll-like receptor 4 has also been reported. Furthermore, MAP kinase kinase kinase (MAP KKK)-related pathways and DNA-PK induce N-terminal phosphorylation of IRF-3. This review summarizes recent observations in the identification of novel signaling pathways leading to IRF-3 activation.

  19. Addressing multiple breast cancer risk factors in African-American women.

    PubMed Central

    Stolley, Melinda R.; Fitzgibbon, Marian L.; Wells, Anita; Martinovich, Zoran

    2004-01-01

    This pilot study explored the acceptability and feasibility of and estimated the effectiveness of a weight loss/breast health intervention designed to reduce breast cancer risk in African-American women ages 35-65. The study had a one-group repeated-measures design and took place in a community setting. Forty-four African-American women were recruited, 35 completed the program, and 30 returned for the one-year follow-up. The pilot intervention was three weeks in duration and included twice-weekly exercise classes and weekly active learning seminars that addressed weight loss, breast health, healthy eating, and leading an active life. Measures included those of behavior related to diet, physical activity, and breast health. Satisfaction questionnaires and focus groups were also used to assess acceptability and cultural competency. Statistical analyses included Paired t-tests and Wilcoxon signed ranks tests. Significant results postintervention showed improved physical activity, dietary, and breast health behaviors. Results suggest the acceptability, feasibility, and effectiveness of this comprehensive weight/loss breast health program in reducing multiple breast cancer risk factors among African-American women. PMID:14746356

  20. [Children with Multiple Risk Factor Exposition Benefit from the German "Strengthening Families Program"].

    PubMed

    Bröning, Sonja; Sack, Peter-Michael; Thomsen, Monika; Thomasius, Rainer

    2016-09-01

    Children with Multiple Risk Factor Exposition Benefit from the German "Strengthening Families Program" The German adaptation of the substance use-preventive family-based Strengthening Families Program 10-14 (SFP, Iowa version) was evaluated in a longitudinal two-year follow-up trial. Participants were N = 292 children with a mean age of twelve years at baseline, and N = 292 parents. We employed a multi-centric, randomized-controlled, two-armed (SFP vs. minimal control condition) study design. Following a "risk moderation hypothesis", we assumed that children with an elevated risk-exposition R(+) would benefit more than children with a low risk-exposition R(-) irrespective of the preventive intervention, and that R(+) under SFP would benefit more than R(+) under the minimal control condition. "Risk-exposition" was measured in correspondence with the Communities That Care Youth Survey-questionnaire. A total of 28 % of children were classified with an elevated risk level. Children's reports confirmed our hypothesis: R(+) report a total of eleven improvements, four of these being significantly more distinct than in the other groups (Anxiety-Depressivity, Punitive Parenting of mother, Punitive Parenting of father, Unbalanced family functioning). In three measures an improvement appears solely in R(+) under SFP (Satisfaction with family functioning, School Attachment and Peer Relationship Quality, Quality of Life). Parents' reports showed a similar tendency, but were less pronounced. PMID:27595812

  1. Discovery of Enhancers of the Secretion of Leukemia Inhibitory Factor for the Treatment of Multiple Sclerosis.

    PubMed

    Vela, Laura; Caballero, Iván; Fang, Leiping; Liu, Qin; Ramón, Fernando; Díez, Emilio; de Los Frailes, Maite

    2016-06-01

    Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that involves activation of T cells, microglia, and astrocytes. There is a clear unmet medical need for MS, as current therapies reduce the relapse rate, but are unable to prevent the neurological deterioration. Leukemia inhibitory factor (LIF) is a proinflammatory cytokine that can also positively modulate the immune response, by inducing the inhibition of myelin-reactive TH17 differentiation, and by promoting oligodendrocyte-mediated myelination. The aim of this project was to find central nervous system (CNS)-permeable and orally available small molecules that upregulate production of endogenous LIF. We describe here the development of a phenotypic assay and screening of 1.7 million compounds to identify LIF enhancers using U87 MG cells. Five chemically tractable series of compounds and a few singletons were selected for further progression. Some of them were also active in a different LIF-expressing cell line and in primary rat astrocytes. Although further studies would be required to deconvolute the targets involved in LIF induction and to confirm activity of hits in more disease-relevant assays, our results have demonstrated the potential of the phenotypic approach to identify specific and chemically tractable small molecules that trigger the production of LIF in relevant cell lines. PMID:26984928

  2. Factors governing the protonation state of Zn-bound histidine in proteins: a DFT/CDM study.

    PubMed

    Lin, Yen-lin; Lim, Carmay

    2004-03-01

    We have performed systematic theoretical studies to elucidate the factors governing the His protonation/deprotonation state in Zn-binding sites, especially those containing the ubiquitous Zn-His-Asp/Glu triad. Specifically, we have addressed the following three questions: (1) How does the transfer of the Zn-bound His imidazole proton to the second-shell Asp/Glu carboxylate oxygen depend on the composition of the other first-shell ligands and the solvent accessibility of the metal-binding site? (2) Can any second-shell ligand with a proton acceptor group such as the backbone carbonyl oxygen also act as a proton acceptor? (3) What is the effect of the Asp/Glu in the Zn-His-Asp/Glu triad on the Zn-bound water protonation state? To address these questions, we used a combination of quantum mechanical and continuum dielectric methods to compute the free energies for deprotonating a Zn-bound imidazole/water in various Zn complexes. The calculations show that whether the Zn-bound His is protonated or deprotonated depends on (1) the solvent accessibility of the metal-binding site, and (2) the Lewis acid ability of Zn, which is indirectly determined by both the first- and the second-shell Zn ligands. The calculations also show that the effect of the Zn-His-Asp/Glu interaction on the nucleophilicity of the Zn-bound water depends on the solvent accessibility of the catalytic Zn site. Furthermore, they show that the Asp/Glu side chain in the Zn-His-Asp/Glu triad can increase the negative charge of its partner, His, and create an anionic hole that may stabilize a cation in buried cavities, provided that the Zn complex is cationic/neutral. The findings of this work are in accord with available experimental data.

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

    PubMed

    Zhu, Binq-Qi; Wang, Yue-Ling

    2016-01-01

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

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

    PubMed

    Zhu, Binq-Qi; Wang, Yue-Ling

    2016-01-01

    Understanding the source and recharge of ground waters is of great significance to our knowledge in hydrological cycles in arid environments over the world. Northern Xinjiang in northwestern China is a significant repository of information relating to the hydrological evolution and climatic changes in central Asia. In this study, two multivariate statistical techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to assess the ground water recharge and its governing factors, with the principal idea of exploring the above techniques to utilize all available hydrogeochemical variables in the quality assessment, which are not considered in the conventional techniques like Stiff and Piper diagrams. Q-mode HCA and R-mode PCA were combined to partition the water samples into seven major water clusters (C1-C7) and three principal components (PC1-PC3, PC1 salinity, PC2 hydroclimate, PC3 contaminant). The water samples C1 + C4 were classified as recharge area waters (Ca-HCO3 water), C2 + C3 as transitional zone waters (Ca-Mg-HCO3-SO4 water), and C5 + C6 + C7 as discharge area waters (Na-SO4 water). Based on the Q-mode PCA scores, three groups of geochemical processes influencing recharge regimes were identified: geogenic (i.e., caused by natural geochemical processes), geomorphoclimatic (caused by topography and climate), and anthropogenic (caused by ground water contamination). It is proposed that differences in recharge mechanism and ground water evolution, and possible bedrock composition difference, are responsible for the chemical genesis of these waters. These will continue to influence the geochemistry of the northern Xinjiang drainage system for a long time due to its steady tectonics and arid climate. This study proved that the chemistry differentiation of ground water can effectively support the identification of ground water recharge and evolution patterns. PMID:26718947

  5. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled

  6. Multiple risk factor intervention reduces carotid atherosclerosis in patients with type 2 diabetes

    PubMed Central

    2014-01-01

    Background Patients with rapid progression of carotid intima media thickness (CIMT) were shown to have a higher future risk for cardiovascular events. The aim of this study was to investigate the impact of multiple risk factor intervention on CIMT progression and to establish whether new cardiovascular surrogate measurements would allow prediction of CIMT changes. Materials and methods In this prospective, open, 2-years study, we included 97 patients with type 2 diabetes and at least two insufficiently treated cardiovascular risk factors, i.e. HbA1c > 7.5% (58 mmol/mol); LDL-cholesterol >3.1 mmol/l or blood pressure >140/90 mmHg. Treatment was intensified according to current guidelines over 3 months with the aim to maintain intensification over 2 years. The primary outcome was the change in CIMT after 2 years. We also assessed markers of mechanical and biochemical endothelial function and endothelial progenitor cells before and after 3 months of treatment intensification. For testing differences between before and after multifactorial treatment measurements we used either the paired student’s t-test or the Wilcoxon signed-rank test, depending on the distribution of the data. Additional, explorative statistical data analysis was done on CIMT progression building a linear multivariate regression model. Results Blood glucose, lipids and blood pressure significantly improved during the first 3 months of intensified treatment, which was sustained over the 2-year study duration. Mean CIMT significantly decreased from baseline to 2 year (0.883 ± 0.120 mm vs. 0.860 ± 0.130 mm; p = 0.021). None of the investigated surrogate measures, however, was able to predict changes in IMT early after treatment intensification. Conclusions Intensification of risk factor intervention in type 2 diabetes results in CIMT regression over a period of 2 years. None of the biomarkers used including endothelial function parameters or endothelial progenitor cells turned out to be useful to

  7. The Cellular Factor NXP2/MORC3 Is a Positive Regulator of Influenza Virus Multiplication

    PubMed Central

    Ver, Lorena S.; Marcos-Villar, Laura; Landeras-Bueno, Sara; Nieto, Amelia

    2015-01-01

    ABSTRACT Transcription and replication of influenza A virus are carried out in the nuclei of infected cells in the context of viral ribonucleoproteins (RNPs). The viral polymerase responsible for these processes is a protein complex composed of the PB1, PB2, and PA proteins. We previously identified a set of polymerase-associated cellular proteins by proteomic analysis of polymerase-containing intracellular complexes expressed and purified from human cells. Here we characterize the role of NXP2/MORC3 in the infection cycle. NXP2/MORC3 is a member of the Microrchidia (MORC) family that is associated with the nuclear matrix and has RNA-binding activity. Influenza virus infection led to a slight increase in NXP2/MORC3 expression and its partial relocalization to the cytoplasm. Coimmunoprecipitation and immunofluorescence experiments indicated an association of NXP2/MORC3 with the viral polymerase and RNPs during infection. Downregulation of NXP2/MORC3 by use of two independent short hairpin RNAs (shRNAs) reduced virus titers in low-multiplicity infections. Consistent with these findings, analysis of virus-specific RNA in high-multiplicity infections indicated a reduction of viral RNA (vRNA) and mRNA after NXP2/MORC3 downregulation. Silencing of NXP2/MORC3 in a recombinant minireplicon system in which virus transcription and replication are uncoupled showed reductions in cat mRNA and chloramphenicol acetyltransferase (CAT) protein accumulation but no alterations in cat vRNA levels, suggesting that NXP2/MORC3 is important for influenza virus transcription. IMPORTANCE Influenza virus infections appear as yearly epidemics and occasional pandemics of respiratory disease, with high morbidity and occasional mortality. Influenza viruses are intracellular parasites that replicate and transcribe their genomic ribonucleoproteins in the nuclei of infected cells, in a complex interplay with host cell factors. Here we characterized the role of the human NXP2/MORC3 protein, a member

  8. Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma.

    PubMed

    Corre, Jill; Labat, Elodie; Espagnolle, Nicolas; Hébraud, Benjamin; Avet-Loiseau, Hervé; Roussel, Murielle; Huynh, Anne; Gadelorge, Mélanie; Cordelier, Pierre; Klein, Bernard; Moreau, Philippe; Facon, Thierry; Fournié, Jean-Jacques; Attal, Michel; Bourin, Philippe

    2012-03-15

    Overexpression of growth differentiation factor 15 (GDF15) by bone marrow mesenchymal stem cells occurs widely in patients with multiple myeloma, but the pathophysiologic effects of GDF15 in this setting remain undefined. GDF15 has been described in numerous solid tumors but never in hematologic malignancies. In this study, we report that GDF15 significantly increases survival of stroma-dependent multiple myeloma cells including primary multiple myeloma cells. In particular, GDF15 conferred resistance to melphalan, bortezomib, and to a lesser extent, lenalidomide in both stroma-dependent and stroma-independent multiple myeloma cells. Akt-dependent signaling was critical to mediate the effects of GDF15, whereas Src and extracellular signal-regulated kinase 1/2 signaling pathways were not involved. Given these results, we tested the clinical significance of plasma concentrations of GDF15 (pGDF15) in 131 patients with multiple myeloma and found that it correlated with disease prognosis. Specifically, patients with high levels of pGDF15 had lower probabilities of event-free and overall survival 30 months after diagnosis than patients with low pGDF15 levels. Our findings suggest that tumor microenvironment-derived GDF15 is a key survival and chemoprotective factor for multiple myeloma cells, which is pathophysiologically linked to both initial parameters of the disease as well as patient survival.

  9. "Governance" or "Governing"?

    ERIC Educational Resources Information Center

    Leslie, David

    This paper draws on four perspectives on power and its exercise in organizations to analyze the practice of governing colleges and universities. The exploration uses political theories (particularly those assessing the legitimacy and effectiveness of stable political entities), leadership studies, analyses of how formal and informal organizations…

  10. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    PubMed

    Poo, Yee Suan; Rudd, Penny A; Gardner, Joy; Wilson, Jane A C; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T; Nakaya, Helder I; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A; Khromykh, Alexander A; Lopez, José A; Suhrbier, Andreas

    2014-12-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  11. Renin-angiotensin system gene polymorphisms as risk factors for multiple sclerosis.

    PubMed

    Živković, Maja; Kolaković, Ana; Stojković, Ljiljana; Dinčić, Evica; Kostić, Smiljana; Alavantić, Dragan; Stanković, Aleksandra

    2016-04-15

    The components of renin-angiotensin system, such as angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II receptor type 1 and 2 (AT1R and AT2R), are expressed in the central nervous system and leukocytes and proposed to be involved in the inflammation and pathogenesis of multiple sclerosis (MS). ACE I/D, AT1R 1166A/C and AT2R -1332A/G are functional polymorphisms associated with phenotypes of diverse chronic inflammatory diseases. The aim of this study was to investigate the association between ACE I/D, AT1R 1166A/C and AT2R -1332A/G gene polymorphisms and MS in Serbian population. A total of 470 MS patients and 478 controls participated in the study. Allele-specific polymerase chain reaction (PCR) was performed for genotyping of the ACE polymorphism. The AT1R and AT2R genotyping was done by duplex PCR and restriction fragment length polymorphism analysis. Both ACE homozygotes, II and DD, were significantly overrepresented in MS patients, compared to controls (χ(2) test p=0.03). Neither genotype nor allele frequencies of AT1R 1166A/C polymorphism were significantly different between patients and controls. Significant overrepresentation of AT2R -1332 AA genotype in female patients, compared to female controls, was detected (OR=1.67, 95%CI=1.13-2.49, χ(2) test p=0.01), suggesting that this genotype could be a gender-specific genetic risk factor for MS.

  12. Global effect of indole-3-acetic acid biosynthesis on multiple virulence factors of Erwinia chrysanthemi 3937.

    PubMed

    Yang, Shihui; Zhang, Qiu; Guo, Jianhua; Charkowski, Amy O; Glick, Bernard R; Ibekwe, A Mark; Cooksey, Donald A; Yang, Ching-Hong

    2007-02-01

    Production of the plant hormone indole-3-acetic acid (IAA) is widespread among plant-associated microorganisms. The non-gall-forming phytopathogen Erwinia chrysanthemi 3937 (strain Ech3937) possesses iaaM (ASAP16562) and iaaH (ASAP16563) gene homologues. In this work, the null knockout iaaM mutant strain Ech138 was constructed. The IAA production by Ech138 was reduced in M9 minimal medium supplemented with l-tryptophan. Compared with wild-type Ech3937, Ech138 exhibited reduced ability to produce local maceration, but its multiplication in Saintpaulia ionantha was unaffected. The pectate lyase production of Ech138 was diminished. Compared with wild-type Ech3937, the expression levels of an oligogalacturonate lyase gene, ogl, and three endopectate lyase genes, pelD, pelI, and pelL, were reduced in Ech138 as determined by a green fluorescent protein-based fluorescence-activated cell sorting promoter activity assay. In addition, the transcription of type III secretion system (T3SS) genes, dspE (a putative T3SS effector) and hrpN (T3SS harpin), was found to be diminished in the iaaM mutant Ech138. Compared with Ech3937, reduced expression of hrpL (a T3SS alternative sigma factor) and gacA but increased expression of rsmA in Ech138 was also observed, suggesting that the regulation of T3SS and pectate lyase genes by IAA biosynthesis might be partially due to the posttranscriptional regulation of the Gac-Rsm regulatory pathway. PMID:17189441

  13. Resource factors for mental health resilience in early childhood: An analysis with multiple methodologies

    PubMed Central

    2013-01-01

    Background Given that relatively little is known about the development of resilience in early childhood, this longitudinal study aimed to identify preschool resource factors associated with young children’s mental health resilience to family adversity. Methods A community sample of 474 young Australian children was assessed in preschool (mean age 4.59 years, 49% male), and again two years later after their transition into formal schooling. At each assessment, standard questionnaires were used to obtain ratings from both parents and teachers about the quality of children’s relationships with parents and teachers, children’s self-concept and self-control, mental health (Strengths and Difficulties Questionnaire), and family adversities (including stressful life events and socioeconomic disadvantage). Results Greater exposure to cumulative family adversities was associated with both greater teacher- and parent-reported child mental health difficulties two years later. Multiple methodologies for operationalizing resilience were used to identify resources associated with resilient mental health outcomes. Higher quality child–parent and child-teacher relationships, and greater child self-concept and self-control were associated with resilient mental health outcomes. With the exception of child-teacher relationships, these resources were also prospective antecedents of subsequent resilient mental health outcomes in children with no pre-existing mental health difficulties. Child–parent relationships and child self-concept generally had promotive effects, being equally beneficial for children facing both low- and high-adversity. Child self-control demonstrated a small protective effect on teacher-reported outcomes, with greater self-control conferring greater protection to children under conditions of high-adversity. Conclusions Findings suggest that early intervention and prevention strategies that focus on fostering child-adult relationship quality, self

  14. Eukaryotic Elongation Factor 2 Kinase Activity Is Controlled by Multiple Inputs from Oncogenic Signaling

    PubMed Central

    Wang, Xuemin; Regufe da Mota, Sergio; Liu, Rui; Moore, Claire E.; Xie, Jianling; Lanucara, Francesco; Agarwala, Usha; Pyr dit Ruys, Sébastien; Vertommen, Didier; Rider, Mark H.; Eyers, Claire E.

    2014-01-01

    Eukaryotic elongation factor 2 kinase (eEF2K), an atypical calmodulin-dependent protein kinase, phosphorylates and inhibits eEF2, slowing down translation elongation. eEF2K contains an N-terminal catalytic domain, a C-terminal α-helical region and a linker containing several regulatory phosphorylation sites. eEF2K is expressed at high levels in certain cancers, where it may act to help cell survival, e.g., during nutrient starvation. However, it is a negative regulator of protein synthesis and thus cell growth, suggesting that cancer cells may possess mechanisms to inhibit eEF2K under good growth conditions, to allow protein synthesis to proceed. We show here that the mTORC1 pathway and the oncogenic Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) pathway cooperate to restrict eEF2K activity. We identify multiple sites in eEF2K whose phosphorylation is regulated by mTORC1 and/or ERK, including new ones in the linker region. We demonstrate that certain sites are phosphorylated directly by mTOR or ERK. Our data reveal that glycogen synthase kinase 3 signaling also regulates eEF2 phosphorylation. In addition, we show that phosphorylation sites remote from the N-terminal calmodulin-binding motif regulate the phosphorylation of N-terminal sites that control CaM binding. Mutations in the former sites, which occur in cancer cells, cause the activation of eEF2K. eEF2K is thus regulated by a network of oncogenic signaling pathways. PMID:25182533

  15. Adaptation of a Counseling Intervention to Address Multiple Cancer Risk Factors among Overweight/Obese Latino Smokers

    ERIC Educational Resources Information Center

    Castro, Yessenia; Fernández, Maria E.; Strong, Larkin L.; Stewart, Diana W.; Krasny, Sarah; Hernandez Robles, Eden; Heredia, Natalia; Spears, Claire A.; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W.

    2015-01-01

    More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social…

  16. Physical and Cognitive-Affective Factors Associated with Fatigue in Individuals with Fibromyalgia: A Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Muller, Veronica; Brooks, Jessica; Tu, Wei-Mo; Moser, Erin; Lo, Chu-Ling; Chan, Fong

    2015-01-01

    Purpose: The main objective of this study was to determine the extent to which physical and cognitive-affective factors are associated with fibromyalgia (FM) fatigue. Method: A quantitative descriptive design using correlation techniques and multiple regression analysis. The participants consisted of 302 members of the National Fibromyalgia &…

  17. Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

    PubMed

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

    2009-05-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging. PMID:19292660

  18. A Multiple Risk Factors Model of the Development of Aggression among Early Adolescents from Urban Disadvantaged Neighborhoods

    ERIC Educational Resources Information Center

    Kim, Sangwon; Orpinas, Pamela; Kamphaus, Randy; Kelder, Steven H.

    2011-01-01

    This study empirically derived a multiple risk factors model of the development of aggression among middle school students in urban, low-income neighborhoods, using Hierarchical Linear Modeling (HLM). Results indicated that aggression increased from sixth to eighth grade. Additionally, the influences of four risk domains (individual, family,…

  19. Multiple-Group Confirmatory Factor Analysis in R--A Tutorial in Measurement Invariance with Continuous and Ordinal Indicators

    ERIC Educational Resources Information Center

    Hirschfeld, Gerrit; von Brachel, Ruth

    2014-01-01

    Multiple-group confirmatory factor analysis (MG-CFA) is among the most productive extensions of structural equation modeling. Many researchers conducting cross-cultural or longitudinal studies are interested in testing for measurement and structural invariance. The aim of the present paper is to provide a tutorial in MG-CFA using the freely…

  20. Multiple Risk Factor Intervention in the Delivery of Primary Health Care to the Elderly: Lessons from Community-Based Programs.

    ERIC Educational Resources Information Center

    Kligman, Evan W.

    Within the past decade the role of the primary care physician caring for older patients has expanded to include counseling and "healthy aging" education to reduce multiple behavior risk factors. Project AGE WELL was a longitudinal study of the impact of a comprehensive and team delivered health promotion program on the health status of the…

  1. Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

    PubMed

    Katada, C; Muto, M; Tanabe, S; Higuchi, K; Sasaki, T; Azuma, M; Ishido, K; Katada, N; Sakuramoto, S; Yamashita, K; Masaki, T; Nakayama, M; Okamoto, M; Koizumi, W

    2014-07-01

    Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal

  2. Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.

    PubMed

    Lindner, Maren; Thümmler, Katja; Arthur, Ariel; Brunner, Sarah; Elliott, Christina; McElroy, Daniel; Mohan, Hema; Williams, Anna; Edgar, Julia M; Schuh, Cornelia; Stadelmann, Christine; Barnett, Susan C; Lassmann, Hans; Mücklisch, Steve; Mudaliar, Manikhandan; Schaeren-Wiemers, Nicole; Meinl, Edgar; Linington, Christopher

    2015-07-01

    Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched 'pre-myelinating' MBP+ / PLP+ oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients.

  3. Weighing Evidence from Mendelian Randomization-Early-Life Obesity as a Causal Factor in Multiple Sclerosis?

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2016-06-01

    In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis. PMID:27351631

  4. Oral rabies vaccination of raccoons and striped skunks with ONRAB® baits: multiple factors influence field immunogenicity.

    PubMed

    Mainguy, Julien; Rees, Erin E; Canac-Marquis, Pierre; Bélanger, Denise; Fehlner-Gardiner, Christine; Séguin, Guylaine; Larrat, Sylvain; Lair, Stéphane; Landry, François; Côté, Nathalie

    2012-10-01

    Multiple control methods have been used in North America to manage the spread of rabies caused by the raccoon (Procyon lotor) rabies virus variant (RRVV). Recently, oral vaccination with ONRAB(®) vaccine baits, which contain an adenovirus rabies glycoprotein recombinant, has been made available as an additional tool for rabies control. Our objectives were to estimate rabies antibody prevalence in wild-caught raccoons and striped skunks (Mephitis mephitis), and identify factors influencing the probability of being antibody positive at the individual level in these species, following oral rabies vaccination (ORV) campaigns in which ONRAB was distributed aerially in 2007-2009 in southern Québec, Canada. Following the aerial distribution of 43-155 ONRAB baits/km(2), the annual percentages of antibody-positive raccoons and skunks varied between 35% and 56% and 11% and 17%, respectively. In raccoons, the probability of being antibody positive was positively associated with age and density of ONRAB distributed, and influenced by the number of previous ORV campaigns conducted. Conversely, this probability was negatively associated with estimated abundance of raccoons in the trapping cell and proportion of residential areas near the raccoon capture location. None of the variables examined explained variation in the probability of being antibody positive in skunks. Our results indicate that the ONRAB density applied during ORV campaigns should be adjusted to account for variations in raccoon population density and presence of residential areas to increase the likelihood of creating an effective immunological barrier against RRVV. The high percentage of juvenile raccoons (annual mean =45 ± 3 [SE]%) and skunks (66 ± 2%) captured during post-ORV monitoring suggests that ORV campaigns should be conducted at least annually to account for the recruitment of naïve individuals into the populations. In Québec, the increasing use of ONRAB coincided with the elimination of rabies

  5. Oral rabies vaccination of raccoons and striped skunks with ONRAB® baits: multiple factors influence field immunogenicity.

    PubMed

    Mainguy, Julien; Rees, Erin E; Canac-Marquis, Pierre; Bélanger, Denise; Fehlner-Gardiner, Christine; Séguin, Guylaine; Larrat, Sylvain; Lair, Stéphane; Landry, François; Côté, Nathalie

    2012-10-01

    Multiple control methods have been used in North America to manage the spread of rabies caused by the raccoon (Procyon lotor) rabies virus variant (RRVV). Recently, oral vaccination with ONRAB(®) vaccine baits, which contain an adenovirus rabies glycoprotein recombinant, has been made available as an additional tool for rabies control. Our objectives were to estimate rabies antibody prevalence in wild-caught raccoons and striped skunks (Mephitis mephitis), and identify factors influencing the probability of being antibody positive at the individual level in these species, following oral rabies vaccination (ORV) campaigns in which ONRAB was distributed aerially in 2007-2009 in southern Québec, Canada. Following the aerial distribution of 43-155 ONRAB baits/km(2), the annual percentages of antibody-positive raccoons and skunks varied between 35% and 56% and 11% and 17%, respectively. In raccoons, the probability of being antibody positive was positively associated with age and density of ONRAB distributed, and influenced by the number of previous ORV campaigns conducted. Conversely, this probability was negatively associated with estimated abundance of raccoons in the trapping cell and proportion of residential areas near the raccoon capture location. None of the variables examined explained variation in the probability of being antibody positive in skunks. Our results indicate that the ONRAB density applied during ORV campaigns should be adjusted to account for variations in raccoon population density and presence of residential areas to increase the likelihood of creating an effective immunological barrier against RRVV. The high percentage of juvenile raccoons (annual mean =45 ± 3 [SE]%) and skunks (66 ± 2%) captured during post-ORV monitoring suggests that ORV campaigns should be conducted at least annually to account for the recruitment of naïve individuals into the populations. In Québec, the increasing use of ONRAB coincided with the elimination of rabies

  6. Identification of the source of elevated hepatocyte growth factor levels in multiple myeloma patients

    PubMed Central

    2014-01-01

    Background Hepatocyte growth factor (HGF) is a pleiotropic cytokine which can lead to cancer cell proliferation, migration and metastasis. In multiple myeloma (MM) patients it is an abundant component of the bone marrow. HGF levels are elevated in 50% of patients and associated with poor prognosis. Here we aim to investigate its source in myeloma. Methods HGF mRNA levels in bone marrow core biopsies from healthy individuals and myeloma patients were quantified by real-time PCR. HGF gene expression profiling in CD138+ cells isolated from bone marrow aspirates of healthy individuals and MM patients was performed by microarray analysis. HGF protein concentrations present in peripheral blood of MM patients were measured by enzyme-linked immunosorbent assay (ELISA). Cytogenetic status of CD138+ cells was determined by fluorescence in situ hybridization (FISH) and DNA sequencing of the HGF gene promoter. HGF secretion in co-cultures of human myeloma cell lines and bone marrow stromal cells was measured by ELISA. Results HGF gene expression profiling in both bone marrow core biopsies and CD138+ cells showed elevated HGF mRNA levels in myeloma patients. HGF mRNA levels in biopsies and in myeloma cells correlated. Quantification of HGF protein levels in serum also correlated with HGF mRNA levels in CD138+ cells from corresponding patients. Cytogenetic analysis showed myeloma cell clones with HGF copy numbers between 1 and 3 copies. There was no correlation between HGF copy number and HGF mRNA levels. Co-cultivation of the human myeloma cell lines ANBL-6 and JJN3 with bone marrow stromal cells or the HS-5 cell line resulted in a significant increase in secreted HGF. Conclusions We here show that in myeloma patients HGF is primarily produced by malignant plasma cells, and that HGF production by these cells might be supported by the bone marrow microenvironment. Considering the fact that elevated HGF serum and plasma levels predict poor prognosis, these findings are of

  7. Factors Influencing Low Level of Women Participation in Literacy Programme in Maiha Local Government Area of Adamawa State

    ERIC Educational Resources Information Center

    Daniel, Aminchi

    2015-01-01

    This study was designed to determine the extent to which poverty, gender stereotype, socio-cultural belief and lack of awareness influence low level of women participation in literacy programme in Maiha Local Government Area of Adamawa State. Survey designed was adopted for the study and a sample consisting of three hundred (300) women who were…

  8. U. S. Government Factors Influencing an Expansion of Study Abroad in the Middle East/North Africa

    ERIC Educational Resources Information Center

    Lane-Toomey, Cara

    2014-01-01

    As the United States continued to grow as a world power throughout the later part of the twentieth century, government funding for international education grew more closely connected to its national security needs. Federal funds have contributed to the growth of Area Studies and studying Less Commonly Taught Languages (LCTLs). Within the last ten…

  9. Variation at Local Government Level in the Support for Families of Severely Disabled Children and the Factors that Affect It

    ERIC Educational Resources Information Center

    Forsyth, Rob; McNally, Richard; James, Peter; Crossland, Kevin; Woolley, Mark; Colver, Allan

    2010-01-01

    Aim: The aim of this study was to examine geographical variability in the support for families caring for children with severe disabilities as well as the relationships between this variability and local government social and educational performance indicators. Method: Data were collected from a cross-sectional, self-completed postal survey of the…

  10. Changes and socioeconomic factors associated with attitudes towards domestic violence among Vietnamese women aged 15–49: findings from the Multiple Indicator Cluster Surveys, 2006–2011

    PubMed Central

    Trinh, Oanh Thi Hoang; Oh, Juhwan; Choi, Sugy; To, Kien Gia; Van Do, Dung

    2016-01-01

    Background Understanding factors associated with domestic violence-supportive attitudes among Vietnamese women is important for designing effective policies to prevent this behavior. Previous studies have largely overlooked risk factors associated with domestic violence-supportive attitudes by women in Vietnam. Objective This paper explores and identifies socioeconomic factors that contribute to domestic violence–supportive attitudes among Vietnamese women using data from the Multiple Indicator Cluster Surveys (MICS). Design Secondary data from two cross-sectional studies (MICS 3, 2006, and MICS 4, 2011) with representative samples (9,471 and 11,663 women, respectively) in Vietnam were analyzed. The prevalence of supportive attitudes toward domestic violence and associations with age, residence region, area, education level, household wealth index, ethnicity, and marital status were estimated using descriptive statistics and multivariate Poisson models, giving estimates of relative risk. Results Overall, the prevalence of acceptance of domestic violence declined between 2006 and 2011 in Vietnam (65.1% vs. 36.1%). Socioeconomic factors associated with women's condoning of domestic violence were age, wealth, education level, and living area. In particular, younger age and low educational attainment were key factors associated with violence-supportive attitudes, and these associations have become stronger over time. Conclusion Higher educational attainment in women is an important predictor of women's attitudes toward domestic violence. To date, Doi Moi and the Vietnamese government's commitment to the Millennium Development Goals may have positively contributed to lowering the acceptance of domestic violence. Tailored interventions that focus on education will be important in further changing attitudes toward domestic violence. PMID:26950567

  11. Real-time particle monitor calibration factors and PM2.5 emission factors for multiple indoor sources.

    PubMed

    Dacunto, Philip J; Cheng, Kai-Chung; Acevedo-Bolton, Viviana; Jiang, Ruo-Ting; Klepeis, Neil E; Repace, James L; Ott, Wayne R; Hildemann, Lynn M

    2013-08-01

    Indoor sources can greatly contribute to personal exposure to particulate matter less than 2.5 μm in diameter (PM2.5). To accurately assess PM2.5 mass emission factors and concentrations, real-time particle monitors must be calibrated for individual sources. Sixty-six experiments were conducted with a common, real-time laser photometer (TSI SidePak™ Model AM510 Personal Aerosol Monitor) and a filter-based PM2.5 gravimetric sampler to quantify the monitor calibration factors (CFs), and to estimate emission factors for common indoor sources including cigarettes, incense, cooking, candles, and fireplaces. Calibration factors for these indoor sources were all significantly less than the factory-set CF of 1.0, ranging from 0.32 (cigarette smoke) to 0.70 (hamburger). Stick incense had a CF of 0.35, while fireplace emissions ranged from 0.44-0.47. Cooking source CFs ranged from 0.41 (fried bacon) to 0.65-0.70 (fried pork chops, salmon, and hamburger). The CFs of combined sources (e.g., cooking and cigarette emissions mixed) were linear combinations of the CFs of the component sources. The highest PM2.5 emission factors per time period were from burned foods and fireplaces (15-16 mg min(-1)), and the lowest from cooking foods such as pizza and ground beef (0.1-0.2 mg min(-1)). PMID:23784066

  12. Frequent expression of multiple myeloma 1/interferon regulatory factor 4 in Burkitt lymphoma.

    PubMed

    Gualco, Gabriela; Queiroga, Eduardo M; Weiss, Lawrence M; Klumb, Claudete E N; Harrington, William J; Bacchi, Carlos E

    2009-04-01

    Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma with endemic, sporadic, and immunodeficiency-associated clinical variants composed of monomorphic medium-sized B cells with a high proliferation rate and a translocation involving the C-MYC locus. Classically, the immunophenotype of Burkitt lymphoma has been considered to be the germinal center type. In most reports, all cases of Burkitt lymphoma are reported to be multiple myeloma 1-negative. multiple myeloma 1 expression is seen in plasma cells and in a small fraction of B cells located in the light zone of germinal centers corresponding to the final step of intra-germinal center B-cell differentiation, and in activated T cells. Therefore, multiple myeloma 1 expression may denote the final step of intra-germinal center B-cell differentiation at the centrocyte stage, as well as the subsequent steps of B-cell maturation toward plasma cells. Unlike most normal germinal center B cells, in which the expression of multiple myeloma 1 and bcl-6 are mutually exclusive, the tumor cells in approximately 50% of multiple myeloma 1-positive DLBCL show coexpression of bcl-6, suggesting that the expression of these proteins may be deregulated. Twenty-five Burkitt lymphoma cases, including 19 associated with HIV, were reported in one of the few studies in the literature; 2 of these cases showed occasional multiple myeloma 1-positive cells, less than the 20% cutoff for positivity. We studied 222 cases of well-characterized Burkitt lymphoma with the classic phenotype and C-MYC translocation and found 90 cases (40.5%) with multiple myeloma 1 nuclear expression, suggesting a late germinal center stage of differentiation.

  13. Las Matematicas: Lenguaje Universal. Nivel 2c: Factores y Multiplos (Mathematics: A Universql Language. Level 2c: Factors and Multiples).

    ERIC Educational Resources Information Center

    Dissemination and Assessment Center for Bilingual Education, Austin, TX.

    This is one of a series of student booklets designed for use in a bilingual mathematics program in grades 6-8. The general format is to present each page in both Spanish and English. The mathematical topics in this booklet include factors, prime and composite numbers, divisibility, and exponents. (MK)

  14. Common Factors Predicting Long-term Changes in Multiple Health Behaviors

    PubMed Central

    BLISSMER, BRYAN; PROCHASKA, JAMES O.; VELICER, WAYNE F.; REDDING, COLLEEN A.; ROSSI, JOSEPH S.; GREENE, GEOFFREY W.; PAIVA, ANDREA; ROBBINS, MARK

    2010-01-01

    This study was designed to assess if there are consistent treatment, stage, severity, effort and demographic effects which predict long-term changes across the multiple behaviors of smoking, diet and sun exposure. A secondary data analysis integrated data from four studies on smoking cessation (N = 3927), three studies on diet (N = 4824) and four studies on sun exposure (N = 6465). Across all three behaviors, behavior change at 24 months was related to treatment, stage of change, problem severity and effort effects measured at baseline. There were no consistent demographic effects. Across multiple behaviors, long-term behavior changes are consistently related to four effects that are dynamic and open to change. Behavior changes were not consistently related to static demographic variables. Future intervention research can target the four effects to determine if breakthroughs can be produced in changing single and multiple behaviors. PMID:20207664

  15. Future Directions in Vulnerability to Depression among Youth: Integrating Risk Factors and Processes across Multiple Levels of Analysis

    PubMed Central

    Hankin, Benjamin L.

    2014-01-01

    Depression is a developmental phenomenon. Considerable progress has been made in describing the syndrome, establishing its prevalence and features, providing clues as to its etiology, and developing evidence-based treatment and prevention options. Despite considerable headway in distinct lines of vulnerability research, there is an explanatory gap in the field ability to more comprehensively explain and predict who is likely to become depressed, when, and why. Still, despite clear success in predicting moderate variance for future depression, especially with empirically rigorous methods and designs, the heterogeneous and multi-determined nature of depression suggests that additional etiologies need to be included to advance knowledge on developmental pathways to depression. This paper advocates for a multiple levels of analysis approach to investigating vulnerability to depression across the lifespan and providing a more comprehensive understanding of its etiology. One example of a multiple levels of analysis model of vulnerabilities to depression is provided that integrates the most accessible, observable factors (e.g., cognitive and temperament risks), intermediate processes and endophenotypes (e.g., information processing biases, biological stress physiology, and neural activation and connectivity), and genetic influences (e.g., candidate genes and epigenetics). Evidence for each of these factors as well as their cross-level integration is provided. Methodological and conceptual considerations important for conducting integrative, multiple levels of depression vulnerability research are discussed. Finally, translational implications for how a multiple levels of analysis perspective may confer additional leverage to reduce the global burden of depression and improve care are considered. PMID:22900513

  16. [Successful treatment of venous thromboembolism with a Factor Xa inhibitor, edoxaban, in patients with lenalidomide-treated multiple myeloma].

    PubMed

    Kawaguchi, Masato; Uchimura, Norio; Okuda, Yuko; Konuma, Satomi; Nehashi, Yoshio

    2015-08-01

    Two multiple myeloma (MM) patients developed venous thromboembolism (VTE) while being treated with lenalidomide and low-dose dexamethasone. Aspirin is recommended for VTE prophylaxis when using lenalidomide/dexamethasone for MM patients with a standard risk of VTE. Despite aspirin administration, however, these two patients experienced VTE. Following VTE development, warfarin and then a Factor Xa inhibitor, edoxaban, were administered. The edoxaban treatment, especially, resulted in favorable and effective control of VTE. Considering these observations, Factor Xa inhibitors may in future become a preferred option for prevention and treatment of VTE when managing MM patients. PMID:26345573

  17. Multiple Regression Analysis of Factors that May Influence Middle School Science Scores

    ERIC Educational Resources Information Center

    Glover, Judith

    2012-01-01

    The purpose of this quantitative multiple regression study was to determine whether a relationship existed between Maryland State Assessment (MSA) reading scores, MSA math scores, gender, ethnicity, age, and MSA science scores. Also examined was if MSA reading scores, MSA math scores, gender, ethnicity, and age can be used in combination or alone…

  18. Prospective Mathematics Teachers' Sense Making of Polynomial Multiplication and Factorization Modeled with Algebra Tiles

    ERIC Educational Resources Information Center

    Caglayan, Günhan

    2013-01-01

    This study is about prospective secondary mathematics teachers' understanding and sense making of representational quantities generated by algebra tiles, the quantitative units (linear vs. areal) inherent in the nature of these quantities, and the quantitative addition and multiplication operations--referent preserving versus referent…

  19. Reassessing the Behavior of Principals as a Multiple-Factor in Teachers' Job Satisfaction.

    ERIC Educational Resources Information Center

    Bogler, Ronit

    This paper reports on a study that examined the effects of three factors on teacher satisfaction: principal leadership style (transformational or transactional), principal decision-making strategy (autocratic versus participative), and teachers' perceptions of their occupation. An overview of each of the three factors is provided. For the study, a…

  20. Multiple Ets factors and interferon regulatory factor-4 modulate CD68 expression in a cell type-specific manner.

    PubMed

    O'Reilly, Dawn; Quinn, Carmel M; El-Shanawany, Tariq; Gordon, Siamon; Greaves, David R

    2003-06-13

    CD68 is a transmembrane glycoprotein expressed in all cells of the mononuclear phagocyte lineage including monocytes and tissue resident macrophages. Deletion analysis of the 5'-flanking sequences of the gene demonstrated that the proximal -150-bp sequence of the CD68 promoter exhibits high level promoter activity in macrophages. Mutations that abolish Ets factor binding at positions -106 and -89 reduce promoter activity in macrophages to 12 and 30%, respectively. Band shift experiments show that PU.1 associates with the -89 site whereas, Elf-1 preferentially binds the -106 Ets binding site and enhances CD68 activity in vitro. Furthermore, chromatin immunoprecipitation experiments confirm that Elf-1 and PU.1 associate with the CD68 proximal promoter in vivo in THP-1 cells. PU.1 does not bind to the CD68 promoter alone but instead forms heterocomplexes with members of the interferon regulatory factor family (IRF) including IRF-4 and IRF-8. IRF-4 and IRF-8 typically mediate transcriptional activation when associated with PU.1 on composite elements. However, our data show that PU.1/IRF-4 and IRF-8 heterocomplexes down-regulate CD68 promoter activity in macrophages and repression is dependent on the integrity of both the IRF and PU.1 half-sites of this composite element. Chromatin immunoprecipitation data reveal that neither IRF-4 nor IRF-8 associate with the CD68 proximal promoter in macrophages in vivo but IRF-4 is associated with the promoter in B lymphocytes. We propose that expression of CD68 in myeloid cells requires the Ets transcription factors Elf-1 and PU.1 and CD68 expression is down-regulated in lymphoid cells by combinatorial interactions between PU.1 and IRF-4.

  1. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.

    PubMed

    Benson, Andrew K; Kelly, Scott A; Legge, Ryan; Ma, Fangrui; Low, Soo Jen; Kim, Jaehyoung; Zhang, Min; Oh, Phaik Lyn; Nehrenberg, Derrick; Hua, Kunjie; Kachman, Stephen D; Moriyama, Etsuko N; Walter, Jens; Peterson, Daniel A; Pomp, Daniel

    2010-11-01

    In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases. PMID:20937875

  2. Role of socio-economic and reproductive factors in the risk of multiple sclerosis.

    PubMed

    Magyari, M

    2015-01-01

    The incidence of multiple sclerosis is increasing in Danish women. Their risk of developing multiple sclerosis has more than doubled in 25 years while it has remained virtually unchanged for men. The explanation for these epidemiological changes should be sought in the environment as they are too rapid to be explained by gene alterations. We investigated the effect of numerous biological social physical and chemical environmental exposures in different periods of life. These data were available from population-based registries and were used in a case-control approach. This study database included all multiple sclerosis cases (n = 1403) from the Danish MS Registry with clinical onset between 2000 and 2004 as well as 35,045 controls drawn by random from the Danish Civil Registration System and matched by sex year of birth and residential municipality at the reference year. Having newborn children reduced the risk of multiple sclerosis (MS) in women but not in men. Childbirths reduced the risk of MS by about 46% during the following 5 years. Even pregnancies terminated early had a protective effect on the risk of developing MS suggesting a temporary immunosuppression during pregnancy. Our data on social behaviour regarding educational level income and relationship stability did not indicate reverse causality. A greater likelihood to be exposed to common infections did not show any effect on the risk of MS neither in puberty nor in adulthood. Socio-economic status and lifestyle expressed in educational level and sanitary conditions in youth were not associated with the risk of MS. PMID:26046554

  3. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    PubMed

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy.

  4. Evaluating the Evidence for the General Factor of Personality across Multiple Inventories

    PubMed Central

    Hopwood, Christopher J.; Wright, Aidan G.C.; Donnellan, M. Brent

    2012-01-01

    A general factor of personality (GFP) has been proposed as the apex of a personality trait hierarchy that explains covariance among the lower-order factors measured by various personality inventories. In this study we evaluated the GFP hypothesis across several personality inventories, unlike most previous research in which the GFP has been derived from individual instruments in isolation. Exploratory analyses did not produce substantial evidence for the existence of a single cross-instrument higher-order factor of factors and efforts to specify a range of GFP-inspired models in a confirmatory framework led to significant estimation difficulties and poor fit to the data. Overall these results fail to support a common GFP that is positioned at the top of a personality trait hierarchy. PMID:22879686

  5. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    SciTech Connect

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  6. Spatially varying relationships between land-cover change and driving factors at multiple sampling scales.

    PubMed

    Du, Shihong; Wang, Qiao; Guo, Luo

    2014-05-01

    Modeling the relationships between environment, human activity, and natural conditions is very important for understanding human-environment interactions. This study aims at examining how these relationships vary over spatial sampling scales and investigating the spatially varying relationships between land-cover changes and driving factors, as well as the variations in the relationships at different sampling scales in the Tibetan Autonomous Prefecture of Qinghai Province, P.R. China. Regular sampling methods are used first to generate eight sets of data points at different scales, and then the values for land-cover changes and the factors are extracted for these data points. Geographically weighted regression (GWR) model is applied to analyze the relationships between land-cover changes and the factors at different sampling scales. The results indicate that the influences of the factors (e.g. the signs, significances, and values of coefficients) change greatly over different sampling scales; similarly, for different types of land-cover changes, the contributions of the factors also vary. Generally, roads, rivers, and lakes contribute greatly to land-cover changes, while villages, temples, and elevations contribute less. A possible reason is that the densities of roads, rivers, and lakes is much greater than those of villages and temples, and the populations in temples and villages are too small to have much effect on land-cover changes. The results demonstrate that the sampling scales have an important influence on the relationships between land-cover change and the factors. PMID:24603033

  7. [Effects of multiple environmental factors on triflulsulfuron-methyl degradation in soils].

    PubMed

    Song, Ning-Hui; Shan, Zheng-Jun; Shi, Li-Li; Guo, Min; Xu, Jing; Kong, De-Yang

    2012-12-01

    Triflulsulfuron-methyl, a widely used sulfonylurea herbicide, has done harm to the soil and crop. Its environment fate was affected by many factors such as physicochemical or biological factors. In order to understand the effects of different environmental factors on the degradation of triflulsulfuron-methyl in soil, simulated indoor incubation experiments were carried out to explore the effects of soil microbe, soil type, dissolved organic matter (DOM), temperature, and soil moisture on triflulsulfuron-methyl degradation in soils. The results showed that different environmental factors such as temperature, soil moisture, soil microorganisms and soil type influenced triflulsulfuron-methyl degradation in different degrees. The increased soil microbial biomass, soil organic matters and DOM were beneficial to the soil degradation of triflulsulfuron-methyl, meanwhile, the decrease in soil pH could accelerate its degradation in soils. The results showed that soil microorganisms were the main factor effecting the degradation of triflulsulfuron-methyl in soil. Our results provided initial data for the conclusion that a set of biological and physiochemical factors coordinately regulate the decay of triflulsulfuron-methyl in soils.

  8. Spatially varying relationships between land-cover change and driving factors at multiple sampling scales.

    PubMed

    Du, Shihong; Wang, Qiao; Guo, Luo

    2014-05-01

    Modeling the relationships between environment, human activity, and natural conditions is very important for understanding human-environment interactions. This study aims at examining how these relationships vary over spatial sampling scales and investigating the spatially varying relationships between land-cover changes and driving factors, as well as the variations in the relationships at different sampling scales in the Tibetan Autonomous Prefecture of Qinghai Province, P.R. China. Regular sampling methods are used first to generate eight sets of data points at different scales, and then the values for land-cover changes and the factors are extracted for these data points. Geographically weighted regression (GWR) model is applied to analyze the relationships between land-cover changes and the factors at different sampling scales. The results indicate that the influences of the factors (e.g. the signs, significances, and values of coefficients) change greatly over different sampling scales; similarly, for different types of land-cover changes, the contributions of the factors also vary. Generally, roads, rivers, and lakes contribute greatly to land-cover changes, while villages, temples, and elevations contribute less. A possible reason is that the densities of roads, rivers, and lakes is much greater than those of villages and temples, and the populations in temples and villages are too small to have much effect on land-cover changes. The results demonstrate that the sampling scales have an important influence on the relationships between land-cover change and the factors.

  9. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL.

    PubMed

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H; Raorane, Manish L; Longkumer, Toshisangba; Pabuayon, Isaiah M; Mutte, Sumanth K; Vardarajan, Adithi R; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor 'no apical meristem' (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  10. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL

    PubMed Central

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H.; Raorane, Manish L.; Longkumer, Toshisangba; Pabuayon, Isaiah M.; Mutte, Sumanth K.; Vardarajan, Adithi R.; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C.; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor ‘no apical meristem’ (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  11. The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms.

    PubMed

    Scott, I C; Anson-Cartwright, L; Riley, P; Reda, D; Cross, J C

    2000-01-01

    The basic helix-loop-helix (bHLH) transcription factor genes Hand1 and Mash2 are essential for placental development in mice. Hand1 promotes differentiation of trophoblast giant cells, whereas Mash2 is required for the maintenance of giant cell precursors, and its overexpression prevents giant cell differentiation. We found that Hand1 expression and Mash2 expression overlap in the ectoplacental cone and spongiotrophoblast, layers of the placenta that contain the giant cell precursors, indicating that the antagonistic activities of Hand1 and Mash2 must be coordinated. MASH2 and HAND1 both heterodimerize with E factors, bHLH proteins that are the DNA-binding partners for most class B bHLH factors and which are also expressed in the ectoplacental cone and spongiotrophoblast. In vitro, HAND1 could antagonize MASH2 function by competing for E-factor binding. However, the Hand1 mutant phenotype cannot be solely explained by ectopic activity of MASH2, as the Hand1 mutant phenotype was not altered by further mutation of Mash2. Interestingly, expression of E-factor genes (ITF2 and ALF1) was down-regulated in the trophoblast lineage prior to giant cell differentiation. Therefore, suppression of MASH2 function, required to allow giant cell differentiation, may occur in vivo by loss of its E-factor partner due to loss of its expression and/or competition from HAND1. In giant cells, where E-factor expression was not detected, HAND1 presumably associates with a different bHLH partner. This may account for the distinct functions of HAND1 in giant cells and their precursors. We conclude that development of the trophoblast lineage is regulated by the interacting functions of HAND1, MASH2, and their cofactors.

  12. Level of education and multiple sclerosis risk after adjustment for known risk factors: The EnvIMS study

    PubMed Central

    Bjørnevik, Kjetil; Riise, Trond; Cortese, Marianna; Holmøy, Trygve; Kampman, Margitta T; Magalhaes, Sandra; Myhr, Kjell-Morten; Wolfson, Christina; Pugliatti, Maura

    2016-01-01

    Background: Several recent studies have found a higher risk of multiple sclerosis (MS) among people with a low level of education. This has been suggested to reflect an effect of smoking and lower vitamin D status in the social class associated with lower levels of education. Objective: The objective of this paper is to investigate the association between level of education and MS risk adjusting for the known risk factors smoking, infectious mononucleosis, indicators of vitamin D levels and body size. Methods: Within the case-control study on Environmental Factors In MS (EnvIMS), 953 MS patients and 1717 healthy controls from Norway reported educational level and history of exposure to putative environmental risk factors. Results: Higher level of education were associated with decreased MS risk (p trend = 0.001) with an OR of 0.53 (95% CI 0.41–0.68) when comparing those with the highest and lowest level of education. This association was only moderately reduced after adjusting for known risk factors (OR 0.61, 95% CI 0.44–0.83). The estimates remained similar when cases with disease onset before age 28 were excluded. Conclusion: These findings suggest that factors related to lower socioeconomic status other than established risk factors are associated with MS risk. PMID:26014605

  13. Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

    PubMed

    Mast, Alan E

    2016-01-01

    Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients.

  14. [Effect of environmental factors on fish community structure in the Huntai River Basin at multiple scales].

    PubMed

    Li, Yan-li; Li, Yan-fen; Xu, Zong-xue

    2014-09-01

    In June 2012, fishes was investigated at 65 sampling sites in the Huntai River basin in Northeast of China. Forty species were collected, belonging to 9 orders, 14 families,33 genera. Cobitidae and Cyprinidae were the dominant fishes in the community structure in the Huntai River basin, accounting for 13. 21% and 65. 83% of the fish community, respectively. There were two types of spatial distribution of fish community, one was distributed in the head water and tributaries in the upstream, and the other was in the plain rivers. Nemachilus nudus, Cobitis granoei and Phoxinus lagowskii dominated the local community in the upper reaches of the Dahuofang Reservoir and shenwo River, while Carassius ayratus and Hemiculter leucisculdus dominated the local community in the plain rivers. CCA (canonical correspondence analysis) was used to distinguish the primary environmental variables that affected the fish community structure. The results indicated fish community was mainly affected by environment factors at watershed and reach scales. Proportions of woodland and urban land, and altitude were three important environmental factors affecting the fish community at the watershed scale. Dissolved oxygen, total nitrogen, pH and habitat inhomogeneity significantly affected the fish community at the reach scale, whereas substrate didn't show significant influence at the microhabitat scale. Environmental factors at watershed scale explained 7. 66% of the variation of fish community structure, environmental factors at reach scale explained 10. 57% of the variation of fish community structure. Environmental factors at reach scale influenced the fish community more significantly.

  15. The role of multiple scattering in twilight zenith sky observations of atmospheric absorbers: Diurnal photochemistry and airmass factors

    NASA Astrophysics Data System (ADS)

    Perliski, Lori Mac

    The ability to properly interpret UV-visible twilight absorption measurements of atmospheric chemical constituents is dependent on how well the optical path, or airmass factor, of light collected by the spectrometer is understood. In the case of direct light measurement, the airmass factor may be calculated from simple geometrical considerations for a spherical atmosphere. In the case of scattered light, a spherical radiative transfer model must be used. A simple single scattering model and a Monte Carlo radiative transfer scheme were developed to study the effects of multiple scattering, aerosol scattering, albedo and refraction on scattered light airmass factors. Stratospheric airmass factors are found to be relatively insensitive to multiple scattering, albedo, refraction and aerosol scattering by background aerosols at fairly short visible wavelengths (about 450 nm). Tropospheric airmass factors, on the other hand, are very sensitive to these processes. Ground albedo, refraction, multiple scattering and aerosol scattering are also important in determining photolysis rates of atmospheric species. It is found that one-dimensional photochemical model calculations of vertical column abundances of several stratospheric chemical constituents are relatively insensitive to changes in photolysis rates due to albedo, refraction and background aerosol scattering, although they are sensitive to multiple scattering. Following the June 1991 eruption of Mt. Pinatubo, OClO and BrO were observed at Fritz Peak Observatory for the first time every. The radiative and photochemical effects of the presence of Pinatubo volcanic aerosols are examined using a one-dimensional photochemical model coupled to a spherical matrix inversion radiative transfer model. Although the heterogeneous removal of NO(x) is not explicitly considered in the photochemical model, the photochemical effects of NO(x) removal may be studied by prescribing the amount of NO(x) removed by heterogeneous chemistry

  16. Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels

    NASA Astrophysics Data System (ADS)

    Wylie, Ryan G.; Ahsan, Shoeb; Aizawa, Yukie; Maxwell, Karen L.; Morshead, Cindi M.; Shoichet, Molly S.

    2011-10-01

    Three-dimensional (3D) protein-patterned scaffolds provide a more biomimetic environment for cell culture than traditional two-dimensional surfaces, but simultaneous 3D protein patterning has proved difficult. We developed a method to spatially control the immobilization of different growth factors in distinct volumes in 3D hydrogels, and to specifically guide differentiation of stem/progenitor cells therein. Stem-cell differentiation factors sonic hedgehog (SHH) and ciliary neurotrophic factor (CNTF) were simultaneously immobilized using orthogonal physical binding pairs, barnase-barstar and streptavidin-biotin, respectively. Barnase and streptavidin were sequentially immobilized using two-photon chemistry for subsequent concurrent complexation with fusion proteins barstar-SHH and biotin-CNTF, resulting in bioactive 3D patterned hydrogels. The technique should be broadly applicable to the patterning of a wide range of proteins.

  17. Risk factors for oxygen toxicity seizures in hyperbaric oxygen therapy: case reports from multiple institutions.

    PubMed

    Seidel, Ruthanna; Carroll, Christopher; Thompson, Debra; Diem, Rena G; Yeboah, Kwabena; Hayes, A J; Hall, Brett; Whelan, Harry T

    2013-01-01

    Oxygen toxicity seizures are a rare but recognized complication of hyperbaric oxygen (HBO2) therapy. Many patients undergoing HBO2 therapy have medical conditions or are taking medications that could contribute to seizures. Previous literature has not extensively reported on these factors in patients experiencing oxygen toxicity seizures. We conducted a chart review at several hyperbaric oxygen centers in the Milwaukee, Wisc., area to explore whether the patients who experienced seizures in the hyperbaric chamber had other medical comorbidities or were on medications which lowered their seizure threshold, thereby contributing to oxygen toxicity seizures. There were a total of seven cases of seizures in five patients. Each patient had risk factors for seizures, including hypercapnia secondary to chronic obstructive pulmonary disease, narcotic withdrawal, alcohol dependence, and antidepressant, tramadol or cephalosporin/ceftriaxone use. We hypothesize that patients who experience oxygen toxicity seizures may have other factors which contribute to the development of these seizures.

  18. A dynamic factor modeling framework for analyzing multiple groundwater head series simultaneously

    NASA Astrophysics Data System (ADS)

    Berendrecht, W. L.; van Geer, F. C.

    2016-05-01

    In this paper we present an approach in which we combine a dynamic factor model (DFM) and predefined response functions to analyze a set of groundwater head series simultaneously. Each groundwater head series is decomposed into: (a) one or more deterministic components as a response to known driving forces, (b) one or more common dynamic factors, representing spatial patterns not related to any of the input series and (c) one specific dynamic factor for each groundwater head series, describing unique variation for that series. The approach reduces the degrees of freedom for each response function, enables the application to irregular observed data, and exploits the correlation between residual series of a set of groundwater head series. The common dynamic factors may be interpreted as spatial patterns due to e.g. limitations in the model specification or concept, spatially correlated errors in input variables, or driving forces which have not been included in the model. In the latter case the model can be applied in the context of an alarming system, e.g. to monitor regional trends. The specific dynamic factor depicts the variation of a particular groundwater head series that cannot be related to any other time series of the set nor to any input series. Therefore the specific dynamic factor is suitable for analyzing local variations and detecting incidental measurement errors, for example in a quality control procedure. The DFM framework is illustrated with a set of 8 groundwater head series and applied for filling gaps in time series, reconstructing high-frequency data, and detecting outliers.

  19. Developing a likely climate scenario from multiple regional climate model simulations with an optimal weighting factor

    NASA Astrophysics Data System (ADS)

    Eum, Hyung-Il; Gachon, Philippe; Laprise, René

    2014-07-01

    This study presents a performance-based comprehensive weighting factor that accounts for the skill of different regional climate models (RCMs), including the effect of the driving lateral boundary condition coming from either atmosphere-ocean global climate models (AOGCMs) or reanalyses. A differential evolution algorithm is employed to identify the optimal relative importance of five performance metrics, and corresponding weighting factors, that include the relative absolute mean error (RAME), annual cycle, spatial pattern, extremes and multi-decadal trend. Based on cumulative density functions built by weighting factors of various RCMs/AOGCMs ensemble simulations, current and future climate projections were then generated to identify the level of uncertainty in the climate scenarios. This study selected the areas of southern Ontario and Québec in Canada as a case study. The main conclusions are as follows: (1) Three performance metrics were found essential, having the greater relative importance: the RAME, annual variability and multi-decadal trend. (2) The choice of driving conditions from the AOGCM had impacts on the comprehensive weighting factor, particularly for the winter season. (3) Combining climate projections based on the weighting factors significantly increased the consistency and reduced the spread among models in the future climate changes. These results imply that the weighting factors play a more important role in reducing the effects of outliers on plausible future climate conditions in regions where there is a higher level of variability in RCM/AOGCM simulations. As a result of weighting, substantial increases in the projected warming were found in the southern part of the study area during summer, and the whole region during winter, compared to the simple equal weighting scheme from RCM runs. This study is an initial step toward developing a likelihood procedure for climate scenarios on a regional scale using equal or different probabilities

  20. Guidelines for management of high-risk African Americans with multiple cardiovascular risk factors: recommendations of an expert consensus panel.

    PubMed

    Williams, Richard Allen; Flack, John M; Gavin, James R; Schneider, Wendy R; Hennekens, Charles H

    2007-01-01

    African Americans have higher rates of cardiovascular disease (CVD) than do Caucasians, which contributes significantly to their reduced life expectancy. Most African American adults have at least one major risk factor for CVD. Nonetheless, African Americans are often underdiagnosed and undertreated, despite presenting to the healthcare system late in their course, often after a CVD event. Patients with multiple risk factors have a CVD risk far greater than the sum of their individual risks. Metabolic syndrome tends to be clustered to a greater degree in African American women. Aggressive management of African Americans is necessary. In this report, we provide guidelines for the management of high-risk African Americans. For each individual risk factor, we address existing data and guidelines in the general population, existing data in African Americans, and proposed guidelines for African Americans based on evidence or extrapolation. In particular, for elevated cholesterol and blood pressure, evidence is emerging that lower is better, so aggressive management strategies are necessary. For dyslipidemia, statins alone will generally reach the goal, but for hypertension, multiple drugs are usually necessary. We conclude that further research in African Americans is necessary to complete the totality of evidence.

  1. Multiple Factors Supporting the Transition to ICT-Rich Learning Environments in India, Turkey, and Chile

    ERIC Educational Resources Information Center

    Light, Daniel

    2010-01-01

    This research project used instrumental case studies of successful schools from the Intel® Teach Essentials Course in Turkey, India and Chile to examine what contextual factors might facilitate teachers' ability to transfer a professional development program about ICT and innovative teaching strategies into their classrooms given the school…

  2. "It Takes a Village" to Support the Vocabulary Development of Children with Multiple Risk Factors

    ERIC Educational Resources Information Center

    Baydar, Nazli; Küntay, Aylin C.; Yagmurlu, Bilge; Aydemir, Nuran; Cankaya, Dilek; Göksen, Fatos; Cemalcilar, Zeynep

    2014-01-01

    Data from a nationally representative sample from Turkey (N = 1,017) were used to investigate the environmental factors that support the receptive vocabulary of 3-year-old children who differ in their developmental risk due to family low economic status and elevated maternal depressive symptoms. Children's vocabulary knowledge was strongly…

  3. Factors Affecting University Entrants' Performance in High-Stakes Tests: A Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Uy, Chin; Manalo, Ronaldo A.; Cabauatan, Ronaldo R.

    2015-01-01

    In the Philippines, students seeking admission to a university are usually required to meet certain entrance requirements, including passing the entrance examinations with questions on IQ and English, mathematics, and science. This paper aims to determine the factors that affect the performance of entrants into business programmes in high-stakes…

  4. Factors Influencing New York Doctoral Graduate Student Satisfaction: A Quantitative Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Nwenyi, Sabina E.

    2013-01-01

    Higher education administrators face challenges in providing a welcoming environment for doctoral students in higher education institutions. Administrators need to identify factors influencing satisfaction of this group of students to provide a supportive environment, reduce attrition rates, and promote persistence. The purpose of this…

  5. Factor Structure of the Revised TOEIC[R] Test: A Multiple-Sample Analysis

    ERIC Educational Resources Information Center

    In'nami, Yo; Koizumi, Rie

    2012-01-01

    This study examined the factor structure of the listening and reading sections of the revised Test of English for International Communication (TOEIC[R]) test. The data from the TOEIC IP (institutional program) test taken by 569 English learners were randomly split into two samples (n = 285 vs. 284). Four models (higher-order, correlated,…

  6. Assessing the Unidimensionality of Psychological Scales: Using Multiple Criteria from Factor Analysis

    ERIC Educational Resources Information Center

    Slocum-Gori, Suzanne L.; Zumbo, Bruno D.

    2011-01-01

    Whenever one uses a composite scale score from item responses, one is tacitly assuming that the scale is dominantly unidimensional. Investigating the unidimensionality of item response data is an essential component of construct validity. Yet, there is no universally accepted technique or set of rules to determine the number of factors to retain…

  7. Evidence for multiple sequences and factors involved in c-myc RNA stability during amphibian oogenesis.

    PubMed

    Lefresne, J; Lemaitre, J M; Selo, M; Goussard, J; Mouton, C; Andeol, Y

    2001-04-01

    To investigate the molecular mechanisms regulating c-myc RNA stability during late amphibian oogenesis, a heterologous system was used in which synthetic Xenopus laevis c-myc transcripts, progressively deleted from their 3' end, were injected into the cytoplasm of two different host axolotl (Ambystoma mexicanum) cells: stage VI oocytes and progesterone-matured oocytes (unfertilized eggs; UFE). This in vivo strategy allowed the behavior of the exogenous c-myc transcripts to be followed and different regions involved in the stability of each intermediate deleted molecule to be identified. Interestingly, these specific regions differ in the two cellular contexts. In oocytes, two stabilizing regions are located in the 3' untranslated region (UTR) and two in the coding sequence (exons II and III) of the RNA. In UFE, the stabilizing regions correspond to the first part of the 3' UTR and to the first part of exon II. However, in UFE, the majority of synthetic transcripts are degraded. This degradation is a consequence of nuclear factors delivered after germinal vesicle breakdown and specifically acting on targeted regions of the RNA. To test the direct implication of these nuclear factors in c-myc RNA degradation, an in vitro system was set up using axolotl germinal vesicle extracts that mimic the in vivo results and confirm the existence of specific destabilizing factors. In vitro analysis revealed that two populations of nuclear molecules are implicated: one of 4.4-5S (50-65 kDa) and the second of 5.4-6S (90-110 kDa). These degrading nuclear factors act preferentially on the coding region of the c-myc RNA and appear to be conserved between axolotl and Xenopus. Thus, this experimental approach has allowed the identification of specific stabilizing sequences in c-myc RNA and the temporal identification of the different factors (cytoplasmic and/or nuclear) involved in post-transcriptional regulation of this RNA during oogenesis. PMID:11284969

  8. Student Government.

    ERIC Educational Resources Information Center

    Morrow, Joyce

    Materials for running a student government program at the junior high school level are provided in three general sections. Section 1 is a description of student government operations. Topics covered include student government responsibilities and activities, student council meeting procedures, parliamentary rules, responsibilities of the…

  9. Factors related to employment status changes in individuals with multiple sclerosis.

    PubMed

    Smith, Megan M; Arnett, Peter A

    2005-10-01

    In a sample of 50 individuals with multiple sclerosis (MS), participants able to work full-time ('W'), those who reduced their hours ('CB') and those who were unemployed ('NW') were compared on demographic and disease variables and symptoms that the participants identified as being responsible for their work status change. The NW group had significantly greater physical disability than the other two groups and significantly more fatigue than the W group. The CB group had significantly more years of education and higher occupational prestige ratings than the NW group. The W group reported significantly greater mood disturbance compared with the NW group. Employment status was unrelated to age, gender, full scale IQ estimate, disease duration, diagnosis duration or cognitive functioning. Ninety per cent of the CB group reported that fatigue was a primary symptom responsible for their work status change, whereas 86% of the NW group reported that broad physical/neurological symptoms were responsible for their change in work status.

  10. Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

    NASA Astrophysics Data System (ADS)

    Huang, Chien-Lin; Hsu, Nien-Sheng

    2016-04-01

    This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

  11. A new method to improve multiplication factor in micro-pixel avalanche photodiodes with high pixel density

    NASA Astrophysics Data System (ADS)

    Sadygov, Z.; Ahmadov, F.; Khorev, S.; Sadigov, A.; Suleymanov, S.; Madatov, R.; Mehdiyeva, R.; Zerrouk, F.

    2016-07-01

    Presented is a new model describing development of the avalanche process in time, taking into account the dynamics of electric field within the depleted region of the diode and the effect of parasitic capacitance shunting individual quenching micro-resistors on device parameters. Simulations show that the effective capacitance of a single pixel, which defines the multiplication factor, is the sum of the pixel capacitance and a parasitic capacitance shunting its quenching micro-resistor. Conclusions obtained as a result of modeling open possibilities of improving the pixel gain in micropixel avalanche photodiodes with high pixel density (or low pixel capacitance).

  12. Factors Affecting Student Success in Distance Learning Courses at a Local California Community College: Joint Governance Perspectives

    ERIC Educational Resources Information Center

    Gonzalez, Luis A.

    2012-01-01

    The purpose of this study was to explore the perspectives of staff and faculty regarding factors affecting student success in distance learning at a California community college (CCC). Participants were members of the leadership group known as the distance learning committee. Data were collected through in-depth interviews using open-ended…

  13. Variation partitioning of diatom species data matrices: Understanding the influence of multiple factors on benthic diatom communities in tropical streams.

    PubMed

    Bere, Taurai; Mangadze, Tinotenda; Mwedzi, Tongai

    2016-10-01

    Elucidating the confounding influence of multiple environmental factors on benthic diatom communities is important in developing water quality predictive models for better guidance of stream management efforts. The objective of this study was to explore the relative impact of metal pollution and hydromorphological alterations in, addition to nutrient enrichment and organic pollution, on diatom taxonomic composition with the view to improve stream diatom-based water quality inference models. Samples were collected twice at 20 sampling stations in the tropical Manyame Catchment, Zimbabwe. Diatom, macroinvertebrate communities and environmental factors were sampled and analysed. The variations in diatom community composition explained by different categories of environmental factors were analysed using canonical correspondence analysis using variance partitioning (partial CCA). The following variations were explained by the different predictor matrices: nutrient levels and organic pollution - 10.4%, metal pollution - 8.3% and hydromorphological factors - 7.9%. Thus, factors other than nutrient levels and organic pollution explain additional significant variation in these diatom communities. Development of diatom-based stream water quality inference models that incorporate metal pollution and hydromorphological alterations, where these are key issues, is thus deemed necessary.

  14. Variation partitioning of diatom species data matrices: Understanding the influence of multiple factors on benthic diatom communities in tropical streams.

    PubMed

    Bere, Taurai; Mangadze, Tinotenda; Mwedzi, Tongai

    2016-10-01

    Elucidating the confounding influence of multiple environmental factors on benthic diatom communities is important in developing water quality predictive models for better guidance of stream management efforts. The objective of this study was to explore the relative impact of metal pollution and hydromorphological alterations in, addition to nutrient enrichment and organic pollution, on diatom taxonomic composition with the view to improve stream diatom-based water quality inference models. Samples were collected twice at 20 sampling stations in the tropical Manyame Catchment, Zimbabwe. Diatom, macroinvertebrate communities and environmental factors were sampled and analysed. The variations in diatom community composition explained by different categories of environmental factors were analysed using canonical correspondence analysis using variance partitioning (partial CCA). The following variations were explained by the different predictor matrices: nutrient levels and organic pollution - 10.4%, metal pollution - 8.3% and hydromorphological factors - 7.9%. Thus, factors other than nutrient levels and organic pollution explain additional significant variation in these diatom communities. Development of diatom-based stream water quality inference models that incorporate metal pollution and hydromorphological alterations, where these are key issues, is thus deemed necessary. PMID:27320742

  15. The Impact of Organizational Factors and Government Policy on Psychiatric Nurses' Family-Focused Practice With Parents Who Have Mental Illness, Their Dependent Children, and Families in Ireland.

    PubMed

    Grant, Anne; Reupert, Andrea

    2016-05-01

    Government policy and organizational factors influence family-focused practice (FFP) in adult mental health services. However, how these aspects shape psychiatric nurses' practice with parents who have mental illness, their dependent children, and families is less well understood. Drawing on the findings of a qualitative study, this article explores the way in which Irish policy and organizational factors might influence psychiatric nurses' FFP, and whether (and how) FFP might be further promoted. A purposive sample of 14 psychiatric nurses from eight mental health services completed semi-structured interviews. The analysis was inductive and presented as thematic networks. Both groups described how policies and organizational culture enabled and/or hindered FFP, with differences between community and acute participants seen. This study indicates a need for policies and organizational supports, including child and family skills training, to promote a whole family approach in adult mental health services.

  16. A case of rhabdomyolysis in the presence of multiple risk factors and dextroamphetamine use.

    PubMed

    Santoro, Jonathan D; Black, Jeanette M; Hamm, L Lee

    2013-06-01

    A 44-year-old Caucasian woman presented to the emergency room with worsening low back pain and loss of cutaneous sensation over the paraspinal muscles from T10 to S1. The patient had ingested the attention-deficit disorder medication dextroamphetamine before engaging in intense physical exercise with subsequent consumption of 3 alcoholic beverages before developing symptoms. The patient's creatine kinase levels remained elevated for 8 days with constant severe pain under standard treatment for rhabdomyolysis. Despite stabilization of pain and laboratory values at discharge, the patient continues to experience low paraspinal back pain. In patients with risk factors for rhabdomyolysis, the use of dextroamphetamine should be monitored closely. Outside our findings, there is no literature linking dextroamphetamine with rhabdomyolysis at nontoxic concentrations or with use of the supplement caffeine containing weight loss supplement, Hydroxycut. The authors believe that further research into the potential role of dextroamphetamine use in the setting of other risk factors for rhabdomyolysis is warranted. PMID:23276898

  17. A case of rhabdomyolysis in the presence of multiple risk factors and dextroamphetamine use.

    PubMed

    Santoro, Jonathan D; Black, Jeanette M; Hamm, L Lee

    2013-06-01

    A 44-year-old Caucasian woman presented to the emergency room with worsening low back pain and loss of cutaneous sensation over the paraspinal muscles from T10 to S1. The patient had ingested the attention-deficit disorder medication dextroamphetamine before engaging in intense physical exercise with subsequent consumption of 3 alcoholic beverages before developing symptoms. The patient's creatine kinase levels remained elevated for 8 days with constant severe pain under standard treatment for rhabdomyolysis. Despite stabilization of pain and laboratory values at discharge, the patient continues to experience low paraspinal back pain. In patients with risk factors for rhabdomyolysis, the use of dextroamphetamine should be monitored closely. Outside our findings, there is no literature linking dextroamphetamine with rhabdomyolysis at nontoxic concentrations or with use of the supplement caffeine containing weight loss supplement, Hydroxycut. The authors believe that further research into the potential role of dextroamphetamine use in the setting of other risk factors for rhabdomyolysis is warranted.

  18. Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression.

    PubMed Central

    Bennett, A M; Hausdorff, S F; O'Reilly, A M; Freeman, R M; Neel, B G

    1996-01-01

    Using transient overexpression and microinjection approaches, we examined SHPTP2's function in growth factor signaling. Overexpression of catalytically inactive SHPTP2 (PTP2CS) but not catalytically inactive SHPTP1, inhibited mitogen-activated protein (MAP) kinase activation and Elk-1 transactivation following epidermal growth factor (EGF) stimulation of 293 cells. An SHPTP2 mutant with both C-terminal tyrosyl phosphorylation sites converted to phenylalanine (PTP2YF) was also without effect; moreover, PTP2YF rescued PTP2CS-induced inhibition of EGF-induced Elk-1 transactivation. PTP2CS did not inhibit transactivation by activated Ras, suggesting that SHPTP2 acts upstream of or parallel to Ras. Neither PTP2CS nor PTP2YF inhibited platelet-derived growth factor (PDGF)-induced Elk-1 transactivation. Thus, protein-tyrosine phosphatase activity, but not tyrosyl phosphorylation of SHPTP2, is required for the immediate-early responses to EGF but not to PDGF. To determine whether SHPTP2 is required later in the cell cycle, we assessed S-phase entry in NIH 3T3 cells microinjected with anti-SHPTP2 antibodies or with a glutathione S-transferase (GST) fusion protein encoding both SH2 domains (GST-SH2). Microinjection of anti-SHPTP2 antibodies prior to stimulation inhibited EGF- but no PDGF- or serum-induced S-phase entry. Anti-SHPTP2 antibodies or GST-SH2 fusion protein could inhibit EGF-induced S-phase entry for up to 8 h after EGF addition. Although MAP kinase activation was detected shortly after EGF stimulation, no MAP kinase activation was detected around the restriction point. Therefore, SHPTP2 is absolutely required for immediate-early and late events induced by some, but not all, growth factors, and the immediate-early and late signal transduction pathways regulated by SHPTP2 are distinguishable. PMID:8622663

  19. Multiple Growth Factors, But Not VEGF, Stimulate Glycosaminoglycan Hyperelongation in Retinal Choroidal Endothelial Cells.

    PubMed

    Al Gwairi, Othman; Osman, Narin; Getachew, Robel; Zheng, Wenhua; Liang, X-L; Kamato, Danielle; Thach, Lyna; Little, Peter J

    2016-01-01

    A major feature of early age-related macular degeneration (AMD) is the thickening of Bruch's membrane in the retina and an alteration in its composition with increased lipid deposition. In certain pathological conditions proteoglycans are responsible for lipid retention in tissues. Growth factors are known to increase the length of glycosaminoglycan chains and this can lead to a large increase in the interaction between proteoglycans and lipids. Using choroidal endothelial cells, we investigated the effects of a number of AMD relevant growth factors TGFβ, thrombin, PDGF, IGF and VEGF on proteoglycan synthesis. Cells were characterized as of endothelial origin using the specific cell markers endothelial nitric oxide synthesis and von Willebrand factor and imaged using confocal microscopy. Cells were treated with growth factors in the presence and absence of the appropriate inhibitors and were radiolabeled with [35S]-SO4. Proteoglycans were isolated by ion exchange chromatography and sized using SDS-PAGE. Radiosulfate incorporation was determined by the cetylpyridinium chloride (CPC) precipitation technique. To measure cellular glycosaminoglycan synthesizing capacity we added xyloside and assessed the xyloside-GAGs by SDS-PAGE. TGFβ, thrombin, PDGF & IGF dose-dependently stimulated radiosulfate incorporation and GAG elongation as well as xyloside-GAG synthesis, however VEGF treatment did not stimulate any changes in proteoglycan synthesis. VEGF did not increase pAKT but caused a large increase in pERK relative to the response to PDGF. Thus, AMD relevant agonists cause glycosaminoglycan hyperelongation of proteoglycans synthesised and secreted by retinal choroidal endothelial cells. The absence of a response to VEGF is intriguing and identifies proteoglycans as a novel potential target in AMD. Future studies will examine the relevance of these changes to enhanced lipid binding and the development of AMD. PMID:27570478

  20. Multiple Growth Factors, But Not VEGF, Stimulate Glycosaminoglycan Hyperelongation in Retinal Choroidal Endothelial Cells

    PubMed Central

    Al Gwairi, Othman; Osman, Narin; Getachew, Robel; Zheng, Wenhua; Liang, X-L.; Kamato, Danielle; Thach, Lyna; Little, Peter J.

    2016-01-01

    A major feature of early age-related macular degeneration (AMD) is the thickening of Bruch's membrane in the retina and an alteration in its composition with increased lipid deposition. In certain pathological conditions proteoglycans are responsible for lipid retention in tissues. Growth factors are known to increase the length of glycosaminoglycan chains and this can lead to a large increase in the interaction between proteoglycans and lipids. Using choroidal endothelial cells, we investigated the effects of a number of AMD relevant growth factors TGFβ, thrombin, PDGF, IGF and VEGF on proteoglycan synthesis. Cells were characterized as of endothelial origin using the specific cell markers endothelial nitric oxide synthesis and von Willebrand factor and imaged using confocal microscopy. Cells were treated with growth factors in the presence and absence of the appropriate inhibitors and were radiolabeled with [35S]-SO4. Proteoglycans were isolated by ion exchange chromatography and sized using SDS-PAGE. Radiosulfate incorporation was determined by the cetylpyridinium chloride (CPC) precipitation technique. To measure cellular glycosaminoglycan synthesizing capacity we added xyloside and assessed the xyloside-GAGs by SDS-PAGE. TGFβ, thrombin, PDGF & IGF dose-dependently stimulated radiosulfate incorporation and GAG elongation as well as xyloside-GAG synthesis, however VEGF treatment did not stimulate any changes in proteoglycan synthesis. VEGF did not increase pAKT but caused a large increase in pERK relative to the response to PDGF. Thus, AMD relevant agonists cause glycosaminoglycan hyperelongation of proteoglycans synthesised and secreted by retinal choroidal endothelial cells. The absence of a response to VEGF is intriguing and identifies proteoglycans as a novel potential target in AMD. Future studies will examine the relevance of these changes to enhanced lipid binding and the development of AMD. PMID:27570478

  1. Energy propagation by transverse waves in multiple flux tube systems using filling factors

    SciTech Connect

    Van Doorsselaere, T.; Gijsen, S. E.; Andries, J.; Verth, G. E-mail: stief.gijsen@wis.kuleuven.be E-mail: g.verth@sheffield.ac.uk

    2014-11-01

    In the last few years, it has been found that transverse waves are present at all times in coronal loops or spicules. Their energy has been estimated with an expression derived for bulk Alfvén waves in homogeneous media, with correspondingly uniform wave energy density and flux. The kink mode, however, is localized in space with the energy density and flux dependent on the position in the cross-sectional plane. The more relevant quantities for the kink mode are the integrals of the energy density and flux over the cross-sectional plane. The present paper provides an approximation to the energy propagated by kink modes in an ensemble of flux tubes by means of combining the analysis of single flux tube kink oscillations with a filling factor for the tube cross-sectional area. This finally allows one to compare the expressions for energy flux of Alfvén waves with an ensemble of kink waves. We find that the correction factor for the energy in kink waves, compared to the bulk Alfvén waves, is between f and 2f, where f is the density filling factor of the ensemble of flux tubes.

  2. Immunological dysfunctions in multiple sclerosis. I. Diminution of 'active' thymus-derived lymphocytes and presence of immunomodulating serum factors.

    PubMed Central

    Kateley, J R; Bazzell, S J

    1979-01-01

    The peripheral blood of twenty-eight patients with multiple sclerosis (MS) was examined for 'active' thymus (TA) derived lymphocytes (PBL) and the presence of serum factors which impair the lymphocyte blastogenic response and the migration of leucocytes from capillary tubes. MS patients exhibited a significant reduction in the level of circulating TA lymphocytes (15.2+/-2.7 vs 22.9+/-2.9, P less than 0.001). Additionally, MS serum markedly impaired the mobility and the mitogen induced blastogenic response of autologous and allogenic (control) PBL. Impairment in the blastogenic response was observed only when serum was added at culture initiation or after 4 hr. The results support the concept of a generalized deficiency in the immune competence of MS patients. The pathophysiological role of a serum suppressive factor is discussed. PMID:312171

  3. Immunological dysfunctions in multiple sclerosis. I. Diminution of 'active' thymus-derived lymphocytes and presence of immunomodulating serum factors.

    PubMed

    Kateley, J R; Bazzell, S J

    1979-02-01

    The peripheral blood of twenty-eight patients with multiple sclerosis (MS) was examined for 'active' thymus (TA) derived lymphocytes (PBL) and the presence of serum factors which impair the lymphocyte blastogenic response and the migration of leucocytes from capillary tubes. MS patients exhibited a significant reduction in the level of circulating TA lymphocytes (15.2+/-2.7 vs 22.9+/-2.9, P less than 0.001). Additionally, MS serum markedly impaired the mobility and the mitogen induced blastogenic response of autologous and allogenic (control) PBL. Impairment in the blastogenic response was observed only when serum was added at culture initiation or after 4 hr. The results support the concept of a generalized deficiency in the immune competence of MS patients. The pathophysiological role of a serum suppressive factor is discussed. PMID:312171

  4. Merging Worlds of Nanomaterials and Biological Environment: Factors Governing Protein Corona Formation on Nanoparticles and Its Biological Consequences

    NASA Astrophysics Data System (ADS)

    Foroozandeh, Parisa; Aziz, Azlan Abdul

    2015-05-01

    Protein corona has became a prevalent subject in the field of nanomedicine owing to its diverse role in determining the efficiency, efficacy, and the ultimate biological fate of the nanomaterials used as a tool to treat and diagnose various diseases. For instance, protein corona formation on the surface of nanoparticles can modify its physicochemical properties and interfere with its intended functionalities in the biological microenvironments. As such, much emphasis should be placed in understanding these complex phenomena that occur at the bio-nano interface. The main aim of this review is to present different factors that are influencing protein-nanoparticle interaction such as physicochemical properties of nanoparticle ( i.e., size and size distribution, shape, composition, surface chemistry, and coatings) and the effect of biological microenvironments. Apart from that, the effect of ignored factors at the bio-nano interface such as temperature, plasma concentration, plasma gradient effect, administration route, and cell observer were also addressed.

  5. Mathematical evaluation of the influence of multiple factors on implant stability quotient values in clinical practice: a retrospective study

    PubMed Central

    Huang, Hairong; Wismeijer, Daniel; Shao, Xianhong; Wu, Gang

    2016-01-01

    Objectives The objective of this study is to mathematically evaluate the influence of multiple factors on implant stability quotient values in clinical practice. Patients and methods Resonance frequency analysis was performed at T1 (measured immediately at the time of implant placement) and at T2 (measured before dental restoration) in 177 patients (329 implants). Using a multivariate linear regression model, we analyzed the influence of the following eleven candidate factors: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting (presence or absence), insertion torque, I-/II-stage healing pattern, implant diameter, implant length, and T1–T2 time interval. Results The following factors were identified to significantly influence the implant stability quotient (ISQ) values at T1: insertion torque, bone grafting, I-/II-stage healing pattern, immediate/delayed implantation, maxillary/mandibular location, implant diameter, and sex. In contrast, the ISQ values at T2 were significantly influenced only by three factors: implant diameter, T1–T2 time interval, and insertion torque. Conclusion Among the eleven candidate factors, seven key factors were found to influence the T1-ISQ values, while only three key factors influenced the T2-ISQ values. Both T1 and T2-ISQ values were found to be influenced by implant diameter and insertion torque. T1 was influenced specifically by the sex of the patient, the location (maxillary or mandibular), the implantation mode (immediate/delayed implantation), the healing stage, and the absence or presence of bone graft materials. PMID:27785040

  6. Sociodemographic Correlates of Modifiable Risk Factors for Hypertension in a Rural Local Government Area of Oyo State South West Nigeria

    PubMed Central

    Abdulsalam, Saliu; Olugbenga-Bello, Adenike; Olarewaju, Olakunle; Abdus-salam, Ismail

    2014-01-01

    Modifiable risk factors of hypertension contribute significantly to all-cause morbidity and mortality worldwide. The study aimed to determine the prevalence of and the association of modifiable risk factors with hypertension in rural community. A cross-sectional study was conducted among 166 male and 201 female adults of 18 years and above using cluster sampling technique. Data were collected using modified WHO STEPS instrument and hypertensive subjects were defined as those with systolic greater than or equal to 140 and diastolic of 90 mmHg. Data were analyzed with SPSS version 17 with level of significance at P < 0.05. The mean age of the subjects was 36.36 (±16.88) years and mean systolic and diastolic pressures were 124 (±16.93) and 76.32 (±11.85) mmHg, respectively. The prevalence of hypertension was high (22.9%) in this rural communities but awareness was low, 10.71%. The prevalence of alcohol consumption, sedentary lifestyle, abnormal weight, inadequate sleep, smoking, significant stress, and female use of hormonal contraceptives was 149 (40.6%), 91 (24.8%), 88 (24.0%), 122 (33.2%), 14 (3.8%), 65 (17.7%), and 53 (26.5%), respectively. Overweight, sex, inadequate sleep, and stress were established as positive predictors of hypertension. The rising prevalence of hypertension and its modifiable risk factors in rural communities require prompt interventions directed at reversing these trends. PMID:25580284

  7. Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia.

    PubMed

    Vital, Marius; Gao, Jiarong; Rizzo, Mike; Harrison, Tara; Tiedje, James M

    2015-03-17

    Butyrate-producing bacteria have an important role in maintaining host health. They are well studied in human and medically associated animal models; however, much less is known for other Vertebrata. We investigated the butyrate-producing community in hindgut-fermenting Mammalia (n = 38), Aves (n = 8) and Reptilia (n = 8) using a gene-targeted pyrosequencing approach of the terminal genes of the main butyrate-synthesis pathways, namely butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). Most animals exhibit high gene abundances, and clear diet-specific signatures were detected with but genes significantly enriched in omnivores and herbivores compared with carnivores. But dominated the butyrate-producing community in these two groups, whereas buk was more abundant in many carnivorous animals. Clustering of protein sequences (5% cutoff) of the combined communities (but and buk) placed carnivores apart from other diet groups, except for noncarnivorous Carnivora, which clustered together with carnivores. The majority of clusters (but: 5141 and buk: 2924) did not show close relation to any reference sequences from public databases (identity <90%) demonstrating a large 'unknown diversity'. Each diet group had abundant signature taxa, where buk genes linked to Clostridium perfringens dominated in carnivores and but genes associated with Ruminococcaceae bacterium D16 were specific for herbivores and omnivores. Whereas 16S rRNA gene analysis showed similar overall patterns, it was unable to reveal communities at the same depth and resolution as the functional gene-targeted approach. This study demonstrates that butyrate producers are abundant across vertebrates exhibiting great functional redundancy and that diet is the primary determinant governing the composition of the butyrate-producing guild.

  8. Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia.

    PubMed

    Vital, Marius; Gao, Jiarong; Rizzo, Mike; Harrison, Tara; Tiedje, James M

    2015-04-01

    Butyrate-producing bacteria have an important role in maintaining host health. They are well studied in human and medically associated animal models; however, much less is known for other Vertebrata. We investigated the butyrate-producing community in hindgut-fermenting Mammalia (n = 38), Aves (n = 8) and Reptilia (n = 8) using a gene-targeted pyrosequencing approach of the terminal genes of the main butyrate-synthesis pathways, namely butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). Most animals exhibit high gene abundances, and clear diet-specific signatures were detected with but genes significantly enriched in omnivores and herbivores compared with carnivores. But dominated the butyrate-producing community in these two groups, whereas buk was more abundant in many carnivorous animals. Clustering of protein sequences (5% cutoff) of the combined communities (but and buk) placed carnivores apart from other diet groups, except for noncarnivorous Carnivora, which clustered together with carnivores. The majority of clusters (but: 5141 and buk: 2924) did not show close relation to any reference sequences from public databases (identity <90%) demonstrating a large 'unknown diversity'. Each diet group had abundant signature taxa, where buk genes linked to Clostridium perfringens dominated in carnivores and but genes associated with Ruminococcaceae bacterium D16 were specific for herbivores and omnivores. Whereas 16S rRNA gene analysis showed similar overall patterns, it was unable to reveal communities at the same depth and resolution as the functional gene-targeted approach. This study demonstrates that butyrate producers are abundant across vertebrates exhibiting great functional redundancy and that diet is the primary determinant governing the composition of the butyrate-producing guild. PMID:25343515

  9. Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia

    PubMed Central

    Vital, Marius; Gao, Jiarong; Rizzo, Mike; Harrison, Tara; Tiedje, James M

    2015-01-01

    Butyrate-producing bacteria have an important role in maintaining host health. They are well studied in human and medically associated animal models; however, much less is known for other Vertebrata. We investigated the butyrate-producing community in hindgut-fermenting Mammalia (n=38), Aves (n=8) and Reptilia (n=8) using a gene-targeted pyrosequencing approach of the terminal genes of the main butyrate-synthesis pathways, namely butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). Most animals exhibit high gene abundances, and clear diet-specific signatures were detected with but genes significantly enriched in omnivores and herbivores compared with carnivores. But dominated the butyrate-producing community in these two groups, whereas buk was more abundant in many carnivorous animals. Clustering of protein sequences (5% cutoff) of the combined communities (but and buk) placed carnivores apart from other diet groups, except for noncarnivorous Carnivora, which clustered together with carnivores. The majority of clusters (but: 5141 and buk: 2924) did not show close relation to any reference sequences from public databases (identity <90%) demonstrating a large ‘unknown diversity'. Each diet group had abundant signature taxa, where buk genes linked to Clostridium perfringens dominated in carnivores and but genes associated with Ruminococcaceae bacterium D16 were specific for herbivores and omnivores. Whereas 16S rRNA gene analysis showed similar overall patterns, it was unable to reveal communities at the same depth and resolution as the functional gene-targeted approach. This study demonstrates that butyrate producers are abundant across vertebrates exhibiting great functional redundancy and that diet is the primary determinant governing the composition of the butyrate-producing guild. PMID:25343515

  10. Multiple factors dictate target selection by Hfq-binding small RNAs

    PubMed Central

    Beisel, Chase L; Updegrove, Taylor B; Janson, Ben J; Storz, Gisela

    2012-01-01

    Hfq-binding small RNAs (sRNAs) in bacteria modulate the stability and translational efficiency of target mRNAs through limited base-pairing interactions. While these sRNAs are known to regulate numerous mRNAs as part of stress responses, what distinguishes targets and non-targets among the mRNAs predicted to base pair with Hfq-binding sRNAs is poorly understood. Using the Hfq-binding sRNA Spot 42 of Escherichia coli as a model, we found that predictions using only the three unstructured regions of Spot 42 substantially improved the identification of previously known and novel Spot 42 targets. Furthermore, increasing the extent of base-pairing in single or multiple base-pairing regions improved the strength of regulation, but only for the unstructured regions of Spot 42. We also found that non-targets predicted to base pair with Spot 42 lacked an Hfq-binding site, folded into a secondary structure that occluded the Spot 42 targeting site, or had overlapping Hfq-binding and targeting sites. By modifying these features, we could impart Spot 42 regulation on non-target mRNAs. Our results thus provide valuable insights into the requirements for target selection by sRNAs. PMID:22388518

  11. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

    PubMed Central

    Lonial, Sagar; Waller, Edmund K.; Richardson, Paul G.; Jagannath, Sundar; Orlowski, Robert Z.; Giver, Cynthia R.; Jaye, David L.; Francis, Dixil; Giusti, Sara; Torre, Claire; Barlogie, Bart; Berenson, James R.; Singhal, Seema; Schenkein, David P.; Esseltine, Dixie-Lee W.; Anderson, Jessica; Xiao, Hugh; Heffner, Leonard T.; Anderson, Kenneth C.

    2005-01-01

    Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production. PMID:16099887

  12. F-theory compactifications with multiple U(1)-factors: constructing elliptic fibrations with rational sections

    NASA Astrophysics Data System (ADS)

    Cvetič, Mirjam; Klevers, Denis; Piragua, Hernan

    2013-06-01

    We study F-theory compactifications with U(1)×U(1) gauge symmetry on elliptically fibered Calabi-Yau manifolds with a rank two Mordell-Weil group. We find that the natural presentation of an elliptic curve {E} with two rational points and a zero point is the generic Calabi-Yau onefold in dP 2. We determine the birational map to its Tate and Weier- strass form and the coordinates of the two rational points in Weierstrass form. We discuss its resolved elliptic fibrations over a general base B and classify them in the case of B = {P} 2. A thorough analysis of the generic codimension two singularities of these elliptic Calabi-Yau manifolds is presented. This determines the general U(1)×U(1)-charges of matter in corresponding F-theory compactifications. The matter multiplicities for the fibration over {P} 2 are determined explicitly and shown to be consistent with anomaly cancellation. Explicit toric examples are constructed, both with U(1)×U(1) and SU(5)×U(1)×U(1) gauge symmetry. As a by-product, we prove the birational equivalence of the two elliptic fibrations with elliptic fibers in the two blow-ups Bl (1,0,0) {P} 2(1, 2, 3) and Bl (0,1,0) {P} 2(1, 1, 2) employing birational maps and extremal transitions.

  13. Involvement of multiple transcription factors for metal-induced spy gene expression in Escherichia coli.

    PubMed

    Yamamoto, Kaneyoshi; Ogasawara, Hiroshi; Ishihama, Akira

    2008-01-20

    Bacteria are directly exposed to metals in environment. To maintain the intracellular metal homeostasis, Escherichia coli contain a number of gene regulation systems, each for response to a specific metal. A periplasmic protein Spy of E. coli was found to be induced upon short-exposure to copper ion in CpxAR-dependent manner. Transcription of the spy gene was also induced by long-exposure to zinc ion. This induction, however, depended on another two-component system BaeSR. Using DNase-I footprinting assay, we identified two BaeR-binding regions on the spy promoter with a direct repeat of the BaeR-box sequence, TCTNCANAA. The zinc-responsive BaeR-binding sites were separated from copper-responsive CpxR-binding site, implying that the spy promoter responds to two species of metal independently through different using sensor-response regulator systems. Since BaeSR-dependent zinc response requires longer time, the induction of spy gene transcription by external zinc may include multiple steps such as through sensing the zinc-induced envelope disorder by BaeSR.

  14. Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease.

    PubMed

    Chen, C J; Wu, M M; Lee, S S; Wang, J D; Cheng, S H; Wu, H Y

    1988-01-01

    The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area.

  15. Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease

    SciTech Connect

    Chen, C.J.; Wu, M.M.; Lee, S.S.; Wang, J.D.; Cheng, S.H.; Wu, H.Y.

    1988-09-01

    The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area.

  16. The multiple complexes formed by the interaction of platelet factor 4 with heparin.

    PubMed Central

    Bock, P E; Luscombe, M; Marshall, S E; Pepper, D S; Holbrook, J J

    1980-01-01

    The anisotropy of the fluorescence of dansyl (5-dimethylaminonaphthalene-1- sulphonyl) groups covalently attached to human platelet factor 4 was used to detect the macromolecular compounds formed when the factor was mixed with heparin. At low heparin/protein ratios a very-high-molecular-weight compound (1) was formed that dissociated to give a smaller compound (2) when excess heparin was added. 2. A large complex was also detected as a precipitate that formed at high protein concentrations in chloride buffer. It contained 15.7% (w/w) polysaccharide, equivalent to four or five heparin tetrasaccharide units per protein tetramer. In this complex, more than one molecule of protein binds to each heparin molecule of molecular weight greater than about 6 X 10(3).3. The stability of these complexes varied with pH, salt concentration and the chain length of the heparin. The limit complexes found in excess of the larger heparins consisted of only one heparin molecule per protein tetramer, and the failure to observe complexes with four heparin molecules/protein tetramer is discussed. PMID:7283972

  17. A retrospective analysis of factors associated with multiple implant failures in maxillae.

    PubMed

    Ekfeldt, A; Christiansson, U; Eriksson, T; Lindén, U; Lundqvist, S; Rundcrantz, T; Johansson, L A; Nilner, K; Billström, C

    2001-10-01

    This retrospective study was designed to verify the factors that influence implant failures. Six prosthodontic clinics in Sweden participated in the study, and together they included a total of 54 patients treated between January 1988 and December 1996. All patients were completely edentulous in the maxilla, and received either a fixed prosthesis or an overdenture supported by at least 4 implants (Brånemark System). Half of the patients belonged to the study group, and an inclusion criterion for this group was that they had lost at least half of their implants. To reduce bias, the patients in the control group were matched to the study group, i.e. they were selected so that both groups were as identical as possible. The results of the study indicate that the control group had a better initial bone support than the study group. Furthermore, the patients in the study group suffered from circumstances that could induce implant failure, such as bruxism, personal grief, depression, as well as addictions to cigarettes, alcohol and/or narcotics. On the study form the clinicians were asked to give their own opinion of the reason for implant failure. The answers given could easily be grouped into 5 different topics, and this experience can be useful to improve patient selection. This study suggests that there are certain factors of importance to consider to prevent a cluster phenomenon of implant failures i.e. lack of bone support, heavy smoking habits and bruxism. PMID:11564105

  18. Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways.

    PubMed

    Yong, Xin; Tang, Bo; Li, Bo-Sheng; Xie, Rui; Hu, Chang-Jiang; Luo, Gang; Qin, Yong; Dong, Hui; Yang, Shi-Ming

    2015-01-01

    Helicobacter pylori (H. pylori) infection is strongly associated with the development of gastric diseases but also with several extragastric diseases. The clinical outcomes caused by H. pylori infection are considered to be associated with a complex combination of host susceptibility, environmental factors and bacterial isolates. Infections involving H. pylori strains that possess the virulence factor CagA have a worse clinical outcome than those involving CagA-negative strains. It is remarkable that CagA-positive H. pylori increase the risk for gastric cancer over the risk associated with H. pylori infection alone. CagA behaves as a bacterial oncoprotein playing a key role in H. pylori-induced gastric cancer. Activation of oncogenic signaling pathways and inactivation of tumor suppressor pathways are two crucial events in the development of gastric cancer. CagA shows the ability to affect the expression or function of vital protein in oncogenic or tumor suppressor signaling pathways via several molecular mechanisms, such as direct binding or interaction, phosphorylation of vital signaling proteins and methylation of tumor suppressor genes. As a result, CagA continuously dysregulates of these signaling pathways and promotes tumorigenesis. Recent research has enriched our understanding of how CagA effects on these signaling pathways. This review summarizes the results of the most relevant studies, discusses the complex molecular mechanism involved and attempts to delineate the entire signaling pathway.

  19. Is a hypothetical melanoma-like neuromelanin the underlying factor essential for the aetiopathogenesis and clinical manifestations of multiple sclerosis?

    PubMed Central

    2013-01-01

    Background Multiple sclerosis (MS) has undergone a significant increase in incidence in the industrialised nations over the last 130 years. Changing environmental factors, possibly infections or a lack of or altered timing of them, determine the prevalence of the disease. Although a plethora of aetiological factors, clearly evident in a group of children with MS, appear relevant, there may nevertheless be a single factor essential for the aetiopathogenesis and clinical manifestation of MS. Description and discussion This hitherto unknown factor is postulated to be a ‘melanoma-like neuromelanin’ (MLN) dependent on the activation of a gene for syncytin-1. An involvement of MLN could explain the diverse findings in the epidemiology, immunology and pathology of MS, requiring a consideration of a complex infectious background, the human leucocyte antigens, as well as cosmic radiation causing geomagnetic disturbances, vitamin D deficiency, smoking, and lower levels of uric acid. Summary In principle, the MLN-based concept is a unifying one, capable of explaining a number of characteristics of the disease. To date, MLN has not been addressed in studies on MS and future work will need to be done on human patients, as there is little or no neuromelanin (the precursor of MLN) in the animals used as experimental models in the study of MS. PMID:23865526

  20. Navigating the “liberation procedure”: a qualitative study of motivating and hesitating factors among people with multiple sclerosis

    PubMed Central

    Ploughman, Michelle; Harris, Chelsea; Hogan, Stephen H; Murray, Cynthia; Murdoch, Michelle; Austin, Mark W; Stefanelli, Mark

    2014-01-01

    Background The debate within the multiple sclerosis (MS) community initiated by the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis and the subsequent liberation procedure placed some people with MS at odds with health care professionals and researchers. Objective This study explored decision making regarding the controversial liberation procedure among people with MS. Subjects and methods Fifteen people with MS (procedure, n=7; no procedure, n=8) participated in audiotaped semistructured interviews exploring their thoughts and experiences related to the liberation procedure. Data were transcribed and analyzed using an iterative, consensus-based, thematic content-analysis approach. Results Participants described an imbalance of motivating factors affirming the procedure compared to hesitating factors that provoked the participant to pause or reconsider when deciding to undergo the procedure. Collegial conversational relationships with trusted sources (eg, MS nurse, neurologist) and ability to critically analyze the CCSVI hypothesis were key hesitating factors. Fundraising, family enthusiasm, and the ease of navigation provided by medical tourism companies helped eliminate barriers to the procedure. Conclusion Knowledge of factors that helped to popularize the liberation procedure in Canada may inform shared decision making concerning this and future controversies in MS. PMID:25228799

  1. The prognostic factors and multiple biomarkers in young patients with colorectal cancer

    PubMed Central

    Wang, Mo-Jin; Ping, Jie; Li, Yuan; Adell, Gunnar; Arbman, Gunnar; Nodin, Bjorn; Meng, Wen-Jian; Zhang, Hong; Yu, Yong-Yang; Wang, Cun; Yang, Lie; Zhou, Zong-Guang; Sun, Xiao-Feng

    2015-01-01

    The incidence of colorectal cancer (CRC) in young patients (≤50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linköping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients. PMID:26013439

  2. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites.

    PubMed

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/.

  3. Multiple factors affect diversity and abundance of ammonia-oxidizing microorganisms in iron mine soil.

    PubMed

    Xing, Yi; Si, Yan-Xiao; Hong, Chen; Li, Yang

    2015-07-01

    Ammonia oxidation by microorganisms is a critical process in the nitrogen cycle. In this study, four soil samples collected from a desert zone in an iron-exploration area and others from farmland and planted forest soil in an iron mine surrounding area. We analyzed the abundance and diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in iron-mining area near the Miyun reservoir using ammonia monooxygenase. A subunit gene (amoA) as molecular biomarker. Quantitative polymerase chain reaction was applied to explore the relationships between the abundance of AOA and AOB and soil physicochemical parameters. The results showed that AOA were more abundant than AOB and may play a more dominant role in the ammonia-oxidizing process in the whole region. PCR-denaturing gradient gel electrophoresis was used to analyze the structural changes of AOA and AOB. The results showed that AOB were much more diverse than AOA. Nitrosospira cluster three constitute the majority of AOB, and AOA were dominated by group 1.1b in the soil. Redundancy analysis was performed to explore the physicochemical parameters potentially important to AOA and AOB. Soil characteristics (i.e. water, ammonia, organic carbon, total nitrogen, available phosphorus, and soil type) were proposed to potentially contribute to the distributions of AOB, whereas Cd was also closely correlated to the distributions of AOB. The community of AOA correlated with ammonium and water contents. These results highlight the importance of multiple drivers in microbial niche formation as well as their affect on ammonia oxidizer composition, both which have significant consequences for ecosystem nitrogen functioning.

  4. Multiple factors affect diversity and abundance of ammonia-oxidizing microorganisms in iron mine soil.

    PubMed

    Xing, Yi; Si, Yan-Xiao; Hong, Chen; Li, Yang

    2015-07-01

    Ammonia oxidation by microorganisms is a critical process in the nitrogen cycle. In this study, four soil samples collected from a desert zone in an iron-exploration area and others from farmland and planted forest soil in an iron mine surrounding area. We analyzed the abundance and diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in iron-mining area near the Miyun reservoir using ammonia monooxygenase. A subunit gene (amoA) as molecular biomarker. Quantitative polymerase chain reaction was applied to explore the relationships between the abundance of AOA and AOB and soil physicochemical parameters. The results showed that AOA were more abundant than AOB and may play a more dominant role in the ammonia-oxidizing process in the whole region. PCR-denaturing gradient gel electrophoresis was used to analyze the structural changes of AOA and AOB. The results showed that AOB were much more diverse than AOA. Nitrosospira cluster three constitute the majority of AOB, and AOA were dominated by group 1.1b in the soil. Redundancy analysis was performed to explore the physicochemical parameters potentially important to AOA and AOB. Soil characteristics (i.e. water, ammonia, organic carbon, total nitrogen, available phosphorus, and soil type) were proposed to potentially contribute to the distributions of AOB, whereas Cd was also closely correlated to the distributions of AOB. The community of AOA correlated with ammonium and water contents. These results highlight the importance of multiple drivers in microbial niche formation as well as their affect on ammonia oxidizer composition, both which have significant consequences for ecosystem nitrogen functioning. PMID:25860433

  5. Factors predicting depression across multiple domains in a national longitudinal sample of Canadian youth.

    PubMed

    Bellamy, Sherry; Hardy, Cindy

    2015-05-01

    This prospective longitudinal study aimed to investigate the strength and relative importance of multiple predictors of depression in youth aged 16 to 20 years. Data were drawn from Statistics Canada's National Longitudinal Survey of Children and Youth (Statistics Canada 2007a, b). Hierarchical regressions were conducted separately by child gender (N = 796 boys; N = 919 girls) for two overlapping samples: mixed parent-child dyads (e.g., biological mothers, fathers and other caregivers; N = 1,715) and a subsample containing only biological mother-child dyads (N = 1,425). Parent-reported data were used from Cycle 1 when the children were aged 4 to 8 years. Parent and child-reported data were used from Cycle 4 when children were aged 10 to 14 years. The outcome measure of depressive symptoms was taken from Cycle 7 when the youth were aged 16 to 20 years. Adolescents reported more depression symptoms than young adults and girls reported more than boys. For boys, higher anxiety/depression scores at ages 4 to 8 years and 10 to 14 years, along with lower self-esteem at 10 to 14 years, predicted higher depression scores. Girls' depression was predicted by loss of a parent by ages 4 to 8 years and higher self-reported anxiety/depression and aggression at ages 10 to 14 years. Among biological mother-child dyads, maternal depression reported by mother when child was aged 4 to 8 years and 10 to 14 years significantly predicted depression for girls. At 10 to 14 years, child-reported lower parental monitoring (girls only) and greater parental rejection (boys and girls) predicted depression at ages 16 to 20 years. PMID:25240908

  6. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion

    SciTech Connect

    Mallick, A.A.; Ishizaka, A.; Stephens, K.E.; Hatherill, J.R.; Tazelaar, H.D.; Raffin, T.A. )

    1989-05-01

    The effect of TNF on nonpulmonary multiple organ damage (MOD) was studied. Since polymorphonuclear leukocytes (PMN) are thought to play an important role in septic or TNF-induced MOD, we investigated both neutrophil sufficient (PMN+) and neutropenic (PMN-) guinea pigs. Sepsis was induced by Escherichia coli administration (2 x 10(9)/kg) or recombinant human TNF (1.4 x 10(6) U/kg) was infused into PMN+ and PMN- guinea pigs. During necropsy, the PMN+/TNF and PMN+/E coli animals exhibited marked damage in the adrenal glands, kidneys and liver as evidenced by hemorrhage, congestion, and PMN sequestration on histopathologic examination. There was also increased tissue albumin accumulation in the adrenal glands, kidneys, spleen, heart, and liver as demonstrated by {sup 125}I-labeled albumin determinations. In contrast, the PMN-/TNF group did not reveal histopathologic damage in any organ system and there was no abnormal organ accumulation of {sup 125}I-albumin. However, in PMN-/E coli animals, marked histopathologic damage in the adrenal glands and liver was evident. Furthermore, there were marked accumulations of {sup 125}I-albumin in the adrenals, heart, kidneys, liver, and spleen. Moreover, the PMN-/E coli guinea pigs had a much greater accumulation (p less than 0.01) of {sup 125}I-albumin in the kidneys than any other group including the PMN+/E coli group. Thus, nonpulmonary MOD in guinea pigs is caused by TNF administration and can be prevented by PMN depletion. However, while E coli administration also caused marked nonpulmonary MOD in neutrophil sufficient guinea pigs, equivalent or greater damage was produced in neutropenic animals. This suggests that while TNF-induced MOD may be primarily mediated by PMN, E coli-induced MOD seems to be mediated by more than PMN.

  7. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites.

    PubMed

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/. PMID:26671811

  8. Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor.

    PubMed

    Liu, Yen-Chin; Liu, Yi-Liang; Su, Jia-Yang; Liu, Guang-Yaw; Hung, Hui-Chih

    2011-01-01

    Both ornithine decarboxylase (ODC) and its regulatory protein, antizyme inhibitor (AZI), can bind with antizyme (AZ), but the latter has a higher AZ-binding affinity. The results of this study clearly identify the critical amino acid residues governing the difference in AZ-binding affinities between human ODC and AZI. Inhibition experiments using a series of ODC mutants suggested that residues 125 and 140 may be the key residues responsible for the differential AZ-binding affinities. The ODC_N125K/M140K double mutant demonstrated a significant inhibition by AZ, and the IC(50) value of this mutant was 0.08 µM, three-fold smaller than that of ODC_WT. Furthermore, the activity of the AZ-inhibited ODC_N125K/M140K enzyme was hardly rescued by AZI. The dissociation constant (K(d)) of the [ODC_N125K/M140K]-AZ heterodimer was approximately 0.02 µM, which is smaller than that of WT_ODC by approximately 10-fold and is very close to the K(d) value of AZI_WT, suggesting that ODC_N125K/M140K has an AZ-binding affinity higher than that of ODC_WT and similar to that of AZI. The efficiency of the AZI_K125N/K140M double mutant in the rescue of AZ-inhibited ODC enzyme activity was less than that of AZI_WT. The K(d) value of [AZI_K125N/K140M]-AZ was 0.18 µM, nine-fold larger than that of AZI_WT and close to the K(d) value of ODC_WT, suggesting that AZI_K125N/K140M has an AZ-binding affinity lower than that of AZI_WT and similar to that of ODC. These data support the hypothesis that the differences in residues 125 and 140 in ODC and AZI are responsible for the differential AZ-binding affinities. PMID:21552531

  9. Governing factors to determine types of submarine fans: Consideration from the model of equilibrium profile of submarine channels

    NASA Astrophysics Data System (ADS)

    Naruse, H.

    2015-12-01

    It has been known that submarine fans are diverse in constitutive architectural elements. Leveed channels are common architectural elements of submarine fans but some of submarine fans lack such self-constructive channels. Also, frontal splays that develops at the end of channels cannot be observed in all of submarine fans. Several researches suggested that this diversity of submarine fans is originated from attributes of sediment supply such as ratio between sand and mud. However, quantitative investigation of these phase changes in types of submarine fans has not been explored yet. Here, this study aims to consider deterministic parameters that govern types of submarine fans, using a theoretical model that assumes submarine channel are in equilibrium condition. The model is based on the 4 equation model of turbidity currents that considers conservation of turbulent kinetic energy. The equilibrium profile is here defined as profiles where turbidity currents are bypassing or depositing uniformly. 1D momentum conservation is considered, and grain-size distribution is approximated to two size classes: channel-forming sands and levee-forming muddy sediments. Widths of channel and levees are calculated from empirical hydraulic geometry. The model predicts length of leveed channels in the equilibrium condition and hydraulic conditions at downstream end of the channels. As a result, depending on boundary condition at upstream end of channels, three possible cases were recognized: (A) submarine channels in which levee-forming muddy sediments are run out at the end of channel, (B) submarine channels in which sandy sediments are run out, and (C) no possible equilibrium profiles that satisfy empirical hydraulic geometry for given boundary conditions. It can be interpreted that these types of results correspond to submarine channels with/without frontal splays and submarine fans without leveed channels. Essentially three parameters are significant to determine types of

  10. Apparatus for measuring the decontamination factor of a multiple filter air-cleaning system

    DOEpatents

    Ortiz, John P.

    1986-01-01

    An apparatus for measuring the overall decontamination factor of first and second filters located in a plenum. The first filter separates the plenum's upstream and intermediate chambers. The second filter separates the plenum's intermediate and downstream chambers. The apparatus comprises an aerosol generator that generates a challenge aerosol. An upstream collector collects unfiltered aerosol which is piped to first and second dilution stages and then to a laser aerosol spectrometer. An intermediate collector collects challenge aerosol that penetrates the first filter. The filtered aerosol is piped to the first dilution stage, diluted, and then piped to the laser aerosol spectrometer which detects single particles. A downstream collector collects challenge aerosol that penetrates both filters. The twice-filtered aerosol is piped to the aerosol spectrometer. A pump and several valves control the movement of aerosol within the apparatus.

  11. Apparatus for measuring the decontamination factor of a multiple filter air-cleaning system

    DOEpatents

    Ortiz, J.P.

    1985-07-03

    An apparatus for measuring the overall decontamination factors of first and second filters located in a plenum. The first filter separates the plenum's upstream and intermediate chambers. The second filter separates the plenum's intermediate and downstream chambers. The apparatus comprises an aerosol generator that generates a challenge aerosol. An upstream collector collects unfiltered aerosol which is piped to first and second dilution stages and then to a laser aerosol spectrometer. An intermediate collector collects challenge aerosol that penetrates the first filter. The filtered aerosol is piped to the first dilution stage, diluted, and then piped to the laser aerosol spectrometer which detects single particles. A downstream collector collects challenge aerosol that penetrates both filters. The twice-filtered aerosol is piped to the aerosol spectrometer. A pump and several valves control the movement of aerosol within the apparatus.

  12. "It takes a village" to support the vocabulary development of children with multiple risk factors.

    PubMed

    Baydar, Nazli; Küntay, Aylin C; Yagmurlu, Bilge; Aydemir, Nuran; Cankaya, Dilek; Göksen, Fatos; Cemalcilar, Zeynep

    2014-04-01

    Data from a nationally representative sample from Turkey (N = 1,017) were used to investigate the environmental factors that support the receptive vocabulary of 3-year-old children who differ in their developmental risk due to family low economic status and elevated maternal depressive symptoms. Children's vocabulary knowledge was strongly associated with language stimulation and learning materials in all families regardless of risk status. Maternal warmth and responsiveness supported vocabulary competence in families of low economic status only when maternal depressive symptoms were low. In families with the highest levels of risk, that is, with depression and economic distress jointly present, support by the extended family and neighbors for caring for the child protected children's vocabulary development against these adverse conditions. The empirical evidence on the positive contribution of extrafamilial support to young children's receptive vocabulary under adverse conditions allows an expansion of our current theorizing about influences on language development.

  13. Relative importance of multiple factors on terrestrial loading of DOC to Arctic river networks

    SciTech Connect

    Kicklighter, David W.; Hayes, Daniel J; Mcclelland, James W; Peterson, Bruce; Mcguire, David; Melillo, Jerry

    2014-01-01

    Terrestrial carbon dynamics influence the contribution of dissolved organic carbon (DOC) to river networks in addition to controlling carbon fluxes between the land surface and the atmosphere. In this study, we use a biogeochemical process model to simulate the lateral transfer of DOC from land to the Arctic Ocean via riverine transport. We estimate that the pan-arctic watershed has contributed, on average, 32 Tg C/yr of DOC to the Arctic Ocean over the 20th century with most coming from the extensive area of boreal deciduous needle-leaved forests and forested wetlands in Eurasian watersheds. We also estimate that the rate of terrestrial DOC loading has been increasing by 0.037 Tg C/yr2 over the 20th century primarily as a result of increases in air temperatures and precipitation. These increases have been partially compensated by decreases in terrestrial DOC loading caused by wildfires. Other environmental factors (CO2 fertilization, ozone pollution, atmospheric nitrogen deposition, timber harvest, agriculture) are estimated to have relatively small effects on terrestrial DOC loading to arctic rivers. The effects of the various environmental factors on terrestrial carbon dynamics have both compensated and enhanced concurrent effects on hydrology to influence terrestrial DOC loading. Future increases in riverine DOC concentrations and export may occur from warming-induced increases in terrestrial DOC production associated with enhanced microbial metabolism and the exposure of additional organic matter from permafrost degradation along with decreases in water yield associated with warming-induced increases in evapotranspiration. Improvements in simulating terrestrial DOC loading to pan-arctic rivers in the future will require better information on the spatial distribution of precipitation and its temporal trends, carbon dynamics of larch-dominated ecosystems in eastern Siberia, and the role of industrial organic effluents on carbon budgets of rivers in western

  14. Multiple Identification and Risks: Examination of Peer Factors Across Multiracial and Single-Race Youth

    PubMed Central

    Choi, Yoonsun; He, Michael; Herrenkohl, Todd I.; Catalano, Richard F.; Toumbourou, John W.

    2012-01-01

    Multiracial youth are thought to be more vulnerable to peer-related risk factors than are single-race youth. However, there have been surprisingly few well-designed studies on this topic. This study empirically investigated the extent to which multiracial youth are at higher risk for peer influenced problem behavior. Data are from a representative and longitudinal sample of youth from Washington State (N = 1,760, mean age = 14.13, 50.9% girls). Of those in the sample, 225 youth self-identified as multiracial (12.8%), 1,259 as White (71.5%), 152 as Latino (8.6%), and 124 as Asian American (7.1%). Results show that multiracial youth have higher rates of violence and alcohol use than Whites and more marijuana use than Asian Americans. Higher levels of socioeconomic disadvantage and single-parent family status partly explained the higher rates of problem behaviors among multiracial youth. Peer risk factors of substance-using or antisocial friends were higher for multiracial youth than Whites, even after socioeconomic variables were accounted for, demonstrating a higher rate of peer risks among multiracial youth. The number of substance-using friends was the most consistently significant correlate and predictor of problems and was highest among multiracial youth. However, interaction tests did not provide consistent evidence of a stronger influence of peer risks among multiracial youth. Findings underscore the importance of a differentiated understanding of vulnerability in order to better target prevention and intervention efforts as well as the need for further research that can help identify and explain the unique experiences and vulnerabilities of multiracial youth. PMID:22395776

  15. Vascular Factors and Multiple Measures of Early Brain Health: CARDIA Brain MRI Study

    PubMed Central

    Launer, Lenore J.; Lewis, Cora E.; Schreiner, Pamela J.; Sidney, Steve; Battapady, Harsha; Jacobs, David R.; Lim, Kelvin O.; D’Esposito, Mark; Zhang, Qian; Reis, Jared; Davatzikos, Christos; Bryan, R. Nick

    2015-01-01

    Objective To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF). Design Cross-sectional brain Magnetic Resonance I (MRI) study. Setting Community based cohort in three U.S. sites. Participants A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study. Primary and Secondary Outcomes 3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function. Results Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01). Conclusion In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia. PMID:25812012

  16. Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

    PubMed Central

    Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

    2014-01-01

    A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

  17. Tunable interplay between epidermal growth factor and cell–cell contact governs the spatial dynamics of epithelial growth

    PubMed Central

    Kim, Jin-Hong; Kushiro, Keiichiro; Graham, Nicholas A.; Asthagiri, Anand R.

    2009-01-01

    Contact-inhibition of proliferation constrains epithelial tissue growth, and the loss of contact-inhibition is a hallmark of cancer cells. In most physiological scenarios, cell–cell contact inhibits proliferation in the presence of other growth-promoting cues, such as soluble growth factors (GFs). How cells quantitatively reconcile the opposing effects of cell–cell contact and GFs, such as epidermal growth factor (EGF), remains unclear. Here, using quantitative analysis of single cells within multicellular clusters, we show that contact is not a “master switch” that overrides EGF. Only when EGF recedes below a threshold level, contact inhibits proliferation, causing spatial patterns in cell cycle activity within epithelial cell clusters. Furthermore, we demonstrate that the onset of contact-inhibition and the timing of spatial patterns in proliferation may be reengineered. Using micropatterned surfaces to amplify cell–cell interactions, we induce contact-inhibition at a higher threshold level of EGF. Using a complementary molecular genetics approach to enhance cell–cell interactions by overexpressing E-cadherin also increases the threshold level of EGF at which contact-inhibition is triggered. These results lead us to propose a state diagram in which epithelial cells transition from a contact-uninhibited state to a contact-inhibited state at a critical threshold level of EGF, a property that may be tuned by modulating the extent of cell–cell contacts. This quantitative model of contact-inhibition has direct implications for how tissue size may be determined and deregulated during development and tumor formation, respectively, and provides design principles for engineering epithelial tissue growth in applications such as tissue engineering. PMID:19549816

  18. Heritabilities of ego strength (factor C), super ego strength (factor G), and self-sentiment (factor Q3) by multiple abstract variance analysis.

    PubMed

    Cattell, R B; Schuerger, J M; Klein, T W

    1982-10-01

    Tested over 3,000 boys (identical and fraternal twins, ordinary sibs, general population) aged 12-18 on Ego Strength, Super Ego Strength, and Self Sentiment. The Multiple Abstract Variance Analysis (MAVA) method was used to obtain estimates of abstract (hereditary, environmental) variances and covariances that contribute to total variation in the three traits. Within-family heritabilities for these traits were about .30, .05, and .65. Between-family heritabilities were .60, .08, and .45. Within-family correlations of genetic and environmental deviations were trivial, unusually so among personality variables, but between-family values showed the usual high negative values, consistent with the law of coercion to the biosocial mean.

  19. The soybean GmbZIP1 transcription factor enhances multiple abiotic stress tolerances in transgenic plants.

    PubMed

    Gao, Shi-Qing; Chen, Ming; Xu, Zhao-Shi; Zhao, Chang-Ping; Li, Liancheng; Xu, Hui-jun; Tang, Yi-miao; Zhao, Xin; Ma, You-Zhi

    2011-04-01

    Abscisic acid (ABA)-responsive element binding proteins (AREBs) are basic domain/leucine zipper transcription factors that bind to the ABA-responsive element (ABRE) in the promoter regions of ABA-inducible genes in plants. A novel bZIP transcription factor gene, GmbZIP1, encoding 438 amino acids with a conserved bZIP domain composed of 60 amino acids was isolated from salt-tolerant soybean cv. Tiefeng 8. Southern blotting showed that only one copy was present in the soybean genome. Phylogenetic analyses showed that GmbZIP1 belonged to the AREB subfamily of the bZIP family and was most closely related to AtABF2 and OsTRAB1. The expression of GmbZIP1 was highly induced by ABA, drought, high salt and low temperature; and GmbZIP1 was expressed in soybean roots, stems and leaves under different stress conditions. GmbZIP1 was localized inside the nuclei of transformed onion epidermal cells. Overexpression of GmbZIP1 enhanced the responses of transgenic plants to ABA and triggered stomatal closure under stresses, potentially leading to improved tolerances to several abiotic stresses such as high salt, low temperature and drought in transgenic plants. Furthermore, overexpression of GmbZIP1 affected the expression of some ABA or stress-related genes involved in regulating stomatal closure in Arabidopsis under ABA, drought and high salt stress conditions. A few AREB elements were detected in the promoter region of those ABA or stress-related genes, suggesting that GmbZIP1 regulates the ABA response or stomatal closure mediated by those downstream genes in transgenic Arabidopsis. Moreover, GmbZIP1 was used to improve the drought tolerance trait of Chinese wheat varieties BS93. Functional analysis showed that overexpression of GmbZIP1 enhanced the drought tolerance of transgenic wheat, and transcripts of GmbZIP1 were detected in transgenic wheat using RT-PCR. In addition, GmbZIP1 overexpression did not result in growth retardation in all transgenic plants, suggesting that Gmb

  20. The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.

    PubMed

    Ingraham, H A; Lala, D S; Ikeda, Y; Luo, X; Shen, W H; Nachtigal, M W; Abbud, R; Nilson, J H; Parker, K L

    1994-10-01

    Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF-1 at other levels of the hypothalamic/pituitary/gonadal axis. In Ftz-F1-disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss of gonadotrope-specific markers, supporting the role of SF-1 in gonadotrope function. In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1-disrupted mice lacked transcripts for three gonadotrope-specific markers (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-subunit of glycoprotein hormones. SF-1 transcripts in the developing mouse pituitary, which first became detectable at embryonic day 13.5-14.5, preceded the appearance of FSH beta and LH beta transcripts. In adult rat pituitary cells, SF-1 transcripts colocalized with immunoreactivity for the gonadotrope-specific LH. Finally, SF-1 interacted with a previously defined promoter element in the glycoprotein hormone alpha-subunit gene, providing a possible mechanism for the impaired gonadotropin expression in Ftz-F1-disrupted mice. These studies establish novel roles of this orphan nuclear receptor in reproductive function.

  1. Microfluidic channel structures speed up mixing of multiple emulsions by a factor of ten

    PubMed Central

    Mbanjwa, Mesuli; Korvink, Jan G.

    2014-01-01

    We present a novel use for channel structures in microfluidic devices, whereby two two-phase emulsions, one created on-chip, the other off-chip, are rapidly mixed with each other in order to allow for the coalescence of one emulsion with the other. This approach has been motivated by the difficulty in introducing aqueous cross linking agents into droplets by utilising conventional approaches. These conventional approaches include continuous introduction of the different aqueous reagents before droplet formation or alternatively formation of individual droplets of each reagent and subsequent droplet merging later in the microfluidic device. We show that our approach can decrease the mixing time for these fluidic systems by a factor greater than 10 times when compared to a standard microfluidic channel without structures, thereby also allowing for additional reaction time within the microfluidic device. This method shows an application for microfluidic channel structures not before demonstrated, also demonstrating an alternative method for introducing reagents such as cross linkers which link polymer chains to form particles, and provides an example where enzymes are immobilized in monodisperse particles. PMID:25332738

  2. Microfluidic channel structures speed up mixing of multiple emulsions by a factor of ten.

    PubMed

    Land, Kevin J; Mbanjwa, Mesuli; Korvink, Jan G

    2014-09-01

    We present a novel use for channel structures in microfluidic devices, whereby two two-phase emulsions, one created on-chip, the other off-chip, are rapidly mixed with each other in order to allow for the coalescence of one emulsion with the other. This approach has been motivated by the difficulty in introducing aqueous cross linking agents into droplets by utilising conventional approaches. These conventional approaches include continuous introduction of the different aqueous reagents before droplet formation or alternatively formation of individual droplets of each reagent and subsequent droplet merging later in the microfluidic device. We show that our approach can decrease the mixing time for these fluidic systems by a factor greater than 10 times when compared to a standard microfluidic channel without structures, thereby also allowing for additional reaction time within the microfluidic device. This method shows an application for microfluidic channel structures not before demonstrated, also demonstrating an alternative method for introducing reagents such as cross linkers which link polymer chains to form particles, and provides an example where enzymes are immobilized in monodisperse particles. PMID:25332738

  3. The intronic splicing code: multiple factors involved in ATM pseudoexon definition.

    PubMed

    Dhir, Ashish; Buratti, Emanuele; van Santen, Maria A; Lührmann, Reinhard; Baralle, Francisco E

    2010-02-17

    Abundance of pseudo splice sites in introns can potentially give rise to innumerable pseudoexons, outnumbering the real ones. Nonetheless, these are efficiently ignored by the splicing machinery, a process yet to be understood completely. Although numerous 5' splice site-like sequences functioning as splicing silencers have been found to be enriched in predicted human pseudoexons, the lack of active pseudoexons pose a fundamental challenge to how these U1snRNP-binding sites function in splicing inhibition. Here, we address this issue by focusing on a previously described pathological ATM pseudoexon whose inhibition is mediated by U1snRNP binding at intronic splicing processing element (ISPE), composed of a consensus donor splice site. Spliceosomal complex assembly demonstrates inefficient A complex formation when ISPE is intact, implying U1snRNP-mediated unproductive U2snRNP recruitment. Furthermore, interaction of SF2/ASF with its motif seems to be dependent on RNA structure and U1snRNP interaction. Our results suggest a complex combinatorial interplay of RNA structure and trans-acting factors in determining the splicing outcome and contribute to understanding the intronic splicing code for the ATM pseudoexon.

  4. Maintenance of Tissue Pluripotency by Epigenetic Factors Acting at Multiple Levels.

    PubMed

    Sadasivam, Devendran A; Huang, Der-Hwa

    2016-02-01

    Pluripotent stem cells often adopt a unique developmental program while retaining certain flexibility. The molecular basis of such properties remains unclear. Using differentiation of pluripotent Drosophila imaginal tissues as assays, we examined the contribution of epigenetic factors in ectopic activation of Hox genes. We found that over-expression of Trithorax H3K4 methyltransferase can induce ectopic adult appendages by selectively activating the Hox genes Ultrabithorax and Sex comb reduced in wing and leg discs, respectively. This tissue-specific inducibility correlates with the presence of paused RNA polymerase II in the promoter-proximal region of these genes. Although the Antennapedia promoter is paused in eye-antenna discs, it cannot be induced by Trx without a reduction in histone variants or their chaperones, suggesting additional control by the nucleosomal architecture. Lineage tracing and pulse-chase experiments revealed that the active state of Hox genes is maintained substantially longer in mutants deficient for HIRA, a chaperone for the H3.3 variant. In addition, both HIRA and H3.3 appeared to act cooperatively with the Polycomb group of epigenetic repressors. These results support the involvement of H3.3-mediated nucleosome turnover in restoring the repressed state. We propose a regulatory framework integrating transcriptional pausing, histone modification, nucleosome architecture and turnover for cell lineage maintenance. PMID:26926299

  5. Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles.

    PubMed

    Udagawa, Osamu; Ishihara, Takaya; Maeda, Maki; Matsunaga, Yui; Tsukamoto, Satoshi; Kawano, Natsuko; Miyado, Kenji; Shitara, Hiroshi; Yokota, Sadaki; Nomura, Masatoshi; Mihara, Katsuyoshi; Mizushima, Noboru; Ishihara, Naotada

    2014-10-20

    Mitochondria are dynamic organelles that change their morphology by active fusion and fission in response to cellular signaling and differentiation. The in vivo role of mitochondrial fission in mammals has been examined by using tissue-specific knockout (KO) mice of the mitochondria fission-regulating GTPase Drp1, as well as analyzing a human patient harboring a point mutation in Drp1, showing that Drp1 is essential for embryonic and neonatal development and neuronal function. During oocyte maturation and aging, structures of various membrane organelles including mitochondria and the endoplasmic reticulum (ER) are changed dynamically, and their organelle aggregation is related to germ cell formation and epigenetic regulation. However, the underlying molecular mechanisms of organelle dynamics during the development and aging of oocytes have not been well understood. Here, we analyzed oocyte-specific mitochondrial fission factor Drp1-deficient mice and found that mitochondrial fission is essential for follicular maturation and ovulation in an age-dependent manner. Mitochondria were highly aggregated with other organelles, such as the ER and secretory vesicles, in KO oocyte, which resulted in impaired Ca(2+) signaling, intercellular communication via secretion, and meiotic resumption. We further found that oocytes from aged mice displayed reduced Drp1-dependent mitochondrial fission and defective organelle morphogenesis, similar to Drp1 KO oocytes. On the basis of these findings, it appears that mitochondrial fission maintains the competency of oocytes via multiorganelle rearrangement. PMID:25264261

  6. Patterns in foliar nutrient resorption stoichiometry at multiple scales: controlling factors and ecosystem consequences (Invited)

    NASA Astrophysics Data System (ADS)

    Reed, S.; Cleveland, C. C.; Davidson, E. A.; Townsend, A. R.

    2013-12-01

    During leaf senescence, nutrient rich compounds are transported to other parts of the plant and this 'resorption' recycles nutrients for future growth, reducing losses of potentially limiting nutrients. Variations in leaf chemistry resulting from nutrient resorption also directly affect litter quality, in turn, regulating decomposition rates and soil nutrient availability. Here we investigated stoichiometric patterns of nitrogen (N) and phosphorus (P) resorption efficiency at multiple spatial scales. First, we assembled a global database to explore nutrient resorption among and within biomes and to examine potential relationships between resorption stoichiometry and ecosystem nutrient status. Next, we used a forest regeneration chronosequence in Brazil to assess how resorption stoichiometry linked with a suite of other nutrient cycling measures and with ideas of how nutrient limitation may change over secondary forest regrowth. Finally, we measured N:P resorption ratios of six canopy tree species in a Costa Rican tropical forest. We calculated species-specific resorption ratios and compared them with patterns in leaf litter and topsoil nutrient concentrations. At the global scale, N:P resorption ratios increased with latitude and decreased with mean annual temperature (MAT) and precipitation (MAP; P<0.001 for each). In particular, we observed a notable switch across latitudes: N:P resorption ratios were generally <1 in latitudes <23° and >1 in latitudes >23°. Focusing on tropical sites in our global dataset we found that, despite fewer data and a restricted latitudinal range, a significant relationship between latitude and N:P resorption ratios persisted (P<0.001). In contrast, tropical N:P resorption ratios did not vary with MAT (P=0.965) and the relationship with MAP was only marginally significant (P=0.089). Data suggest that soil type, at least in part, helps explain N:P resorption patterns across tropical latitudes: plants on more weathered soils (Oxisols

  7. Land use as an explanatory factor for potential phosphorus loss risk, assessed by P indices and their governing parameters.

    PubMed

    Zhou, Bin; Vogt, Rolf D; Lu, Xueqiang; Yang, Xiaoguang; Lü, Changwei; Mohr, Christian W; Zhu, Liang

    2015-08-01

    The total level of phosphorus (P) and the distribution of P pools in the topsoil are significantly affected by the excessive application of mineral and organic fertilizers connected with intensive agriculture. This leads to an increased potential risk for P loss, and then contributes to freshwater eutrophication. Soil test P (STP), P sorption index (PSI) and degree of P saturation (DPS) are commonly applied as proxies for assessing the risk of P loss. Although conceptually based, the empirical relationships between these operationally defined proxies and the actual P flux exhibit large spatial variations. Herein, a comprehensive synoptic study and monitoring of soil has been conducted in a watershed in north-eastern China. A set of conventional indicators for soil P loss risk were measured along with the main P pools, P sorption indices, texture, organic matter, as well as Fe and Al oxides and other mineral compositions. Moreover, detailed soil P speciation was conducted using phosphorus nuclear magnetic resonance ((31)P NMR) spectroscopy. In addition, phosphatase activities in the soils were determined for each land use soil category. The results reflected that the soil content of total P, total inorganic P and STP increased significantly following the order of increasing management intensity. STP, being strongly coupled to the application of P fertilizers, was a strong explanatory factor for the spatial differences in DPS - both between and within different land uses. The dominant inorganic and organic P species in the soils were orthophosphate and monoester-P, respectively. Their contents were oppositely correlated with the degree of management influence, with the amount of orthophosphate positively related. Alkaline phosphomonoesterase (AlP) represented the highest activities among the four representative phosphatases, i.e. enzymes that hydrolyze organic P - releasing labile orthophosphate. Orchard soils were found to contain the highest levels of monoester P

  8. On the factors governing water vapor turbulence mixing in the convective boundary layer over land: Concept and data analysis technique using ground-based lidar measurements.

    PubMed

    Pal, Sandip

    2016-06-01

    The convective boundary layer (CBL) turbulence is the key process for exchanging heat, momentum, moisture and trace gases between the earth's surface and the lower part of the troposphere. The turbulence parameterization of the CBL is a challenging but important component in numerical models. In particular, correct estimation of CBL turbulence features, parameterization, and the determination of the contribution of eddy diffusivity are important for simulating convection initiation, and the dispersion of health hazardous air pollutants and Greenhouse gases. In general, measurements of higher-order moments of water vapor mixing ratio (q) variability yield unique estimates of turbulence in the CBL. Using the high-resolution lidar-derived profiles of q variance, third-order moment, and skewness and analyzing concurrent profiles of vertical velocity, potential temperature, horizontal wind and time series of near-surface measurements of surface flux and meteorological parameters, a conceptual framework based on bottom up approach is proposed here for the first time for a robust characterization of the turbulent structure of CBL over land so that our understanding on the processes governing CBL q turbulence could be improved. Finally, principal component analyses will be applied on the lidar-derived long-term data sets of q turbulence statistics to identify the meteorological factors and the dominant physical mechanisms governing the CBL turbulence features.

  9. On the factors governing water vapor turbulence mixing in the convective boundary layer over land: Concept and data analysis technique using ground-based lidar measurements.

    PubMed

    Pal, Sandip

    2016-06-01

    The convective boundary layer (CBL) turbulence is the key process for exchanging heat, momentum, moisture and trace gases between the earth's surface and the lower part of the troposphere. The turbulence parameterization of the CBL is a challenging but important component in numerical models. In particular, correct estimation of CBL turbulence features, parameterization, and the determination of the contribution of eddy diffusivity are important for simulating convection initiation, and the dispersion of health hazardous air pollutants and Greenhouse gases. In general, measurements of higher-order moments of water vapor mixing ratio (q) variability yield unique estimates of turbulence in the CBL. Using the high-resolution lidar-derived profiles of q variance, third-order moment, and skewness and analyzing concurrent profiles of vertical velocity, potential temperature, horizontal wind and time series of near-surface measurements of surface flux and meteorological parameters, a conceptual framework based on bottom up approach is proposed here for the first time for a robust characterization of the turbulent structure of CBL over land so that our understanding on the processes governing CBL q turbulence could be improved. Finally, principal component analyses will be applied on the lidar-derived long-term data sets of q turbulence statistics to identify the meteorological factors and the dominant physical mechanisms governing the CBL turbulence features. PMID:26950615

  10. Multiple Risk Factors of Alcoholic and Non-Alcoholic Myocardial Infarction Patients

    PubMed Central

    Harisharan; Singh, Awnish Kumar; Dangal, Nidhu Ram; Surapaneni, Krishna Mohan; Joshi, Ashish

    2016-01-01

    Background: Myocardial infarction (MI) is one of the most critical medical emergency and contributor to morbidity and mortality worldwide. Myocardial infarction is the most common form of coronary heart disease and leading cause of premature death. Past century has seen substantial advancement in the field of medical sciences but still mortality trends due to myocardial infarction is increasing in developing countries including India. We have conducted this study to compare the Sociodemographic characteristics of alcoholic and non alcoholic MI patients admitted in coronary care unit of Saveetha Medical College, Chennai, India. Methods: An exploratory cross sectional study was performed by enrolling a convenient sample of 100 Myocardial Infarction patients. Information about Sociodemographic characteristics, past medical history, alcohol and tobacco intake, physical activity, psychological stress and biochemical measurements was gathered. Results: The mean age of the respondents was 46 (SD=6) years and majority of them were male i.e. 82%. 100% married and 89% literate, there were 24% past and 22% present alcoholics. Consumption of alcohol on a monthly, weekly and daily basis was 8%, 11% and 5% respectively. Preference to brandy was 67%, rum was 21% and that the beer was 12%. Current smoker were 20% and former were 11%. 93% and 52% respondents were under medication of beta blocker and angiotensin-converting-enzyme (ACE) inhibitors respectively. Conclusion: Worldwide, MI is the most common cause of mortality and morbidity and hence early diagnosis and management is most essential. Results from our study revealed that, participants had sedentary lifestyles where risk factors of MI such as alcohol consumption, and smoking does existed. PMID:26234988

  11. Hypoxia converts the myogenic action of insulin-like growth factors into mitogenic action by differentially regulating multiple signaling pathways

    PubMed Central

    Ren, Hongxia; Accili, Domenico; Duan, Cunming

    2010-01-01

    Insulin-like growth factors (IGFs) stimulate myoblast proliferation and differentiation. It remains elusive how these mutually exclusive cellular responses are elicited by the same growth factor. Here we report that whereas IGF promotes myoblast differentiation under normoxia, it stimulates proliferation under hypoxia. Hypoxia activates the HIF-1 transcriptional program and knockdown of HIF-1α changes the mitogenic action of IGF into myogenic action under hypoxia. Conversely, overexpression of HIF-1α abolishes the myogenic effect of IGF under normoxia. Under normoxia, IGF activates the Akt-mTOR, p38, and Erk1/2 MAPK pathways. Hypoxia suppresses basal and IGF-induced Akt-mTOR and p38 activity, whereas it enhances and prolongs IGF-induced Erk1/2 activation in a HIF-1–dependent fashion. Activation of Akt-mTOR and p38 promotes myogenesis, and p38 also inhibits proliferation. Activation of Erk stimulates myoblast proliferation but inhibits differentiation. These results suggest that hypoxia converts the myogenic action of IGFs into mitogenic action by differentially regulating multiple signaling pathways via HIF-1-dependent mechanisms. Our findings provide a mechanistic explanation for the paradoxical actions of IGFs during myogenesis and reveal a novel mechanism by which cells sense and integrate growth factor signals and oxygen availability in their microenvironments. PMID:20231451

  12. ABI-like transcription factor gene TaABL1 from wheat improves multiple abiotic stress tolerances in transgenic plants.

    PubMed

    Xu, Dong-Bei; Gao, Shi-Qing; Ma, You-Zhi; Xu, Zhao-Shi; Zhao, Chang-Ping; Tang, Yi-Miao; Li, Xue-Yin; Li, Lian-Cheng; Chen, Yao-Feng; Chen, Ming

    2014-12-01

    The phytohormone abscisic acid (ABA) plays crucial roles in adaptive responses of plants to abiotic stresses. ABA-responsive element binding proteins (AREBs) are basic leucine zipper transcription factors that regulate the expression of downstream genes containing ABA-responsive elements (ABREs) in promoter regions. A novel ABI-like (ABA-insensitive) transcription factor gene, named TaABL1, containing a conserved basic leucine zipper (bZIP) domain was cloned from wheat. Southern blotting showed that three copies were present in the wheat genome. Phylogenetic analyses indicated that TaABL1 belonged to the AREB subfamily of the bZIP transcription factor family and was most closely related to ZmABI5 in maize and OsAREB2 in rice. Expression of TaABL1 was highly induced in wheat roots, stems, and leaves by ABA, drought, high salt, and low temperature stresses. TaABL1 was localized inside the nuclei of transformed wheat mesophyll protoplast. Overexpression of TaABL1 enhanced responses of transgenic plants to ABA and hastened stomatal closure under stress, thereby improving tolerance to multiple abiotic stresses. Furthermore, overexpression of TaABL1 upregulated or downregulated the expression of some stress-related genes controlling stomatal closure in transgenic plants under ABA and drought stress conditions, suggesting that TaABL1 might be a valuable genetic resource for transgenic molecular breeding.

  13. Evidence for multiple bone resorption-stimulating factors produced by normal human keratinocytes in culture.

    PubMed

    Fried, R M; Voelkel, E F; Rice, R H; Levine, L; Tashjian, A H

    1988-06-01

    Conditioned medium from cultured normal human foreskin keratinocytes enhanced the release of calcium from neonatal mouse calvaria in organ culture. Unfractionated keratinocyte-conditioned medium (KCM) stimulated bone resorption in a dose-dependent manner, but it did not increase the concentration of prostaglandin E2 (PGE2) in the bone culture medium until a maximal dose of KCM for resorption was used. Furthermore, inhibitors of PGE2 synthesis, indomethacin, ibuprofen, and piroxicam, did not inhibit KCM-induced calcium release. High concentrations of KCM increased cAMP production by calvaria in the presence of isobutylmethylxanthine, but the increase was small compared with that produced by a dose of bovine PTH that caused a similar level of bone resorption. The bone resorption-stimulating activity of KCM was not lost after incubation at 56 C for 60 min, but it was lost after heating at 100 C for 10 min. Fractionation of KCM by gel filtration chromatography revealed two distinct peaks of bone resorption-stimulating activity. One peak, KCMI, caused a significant increase in bone resorption at 2 micrograms protein/ml. KCMI did not increase medium PGE2, and inhibition of PGE2 synthesis in bone had no effect on KCMI-induced bone resorption. KCMI failed to increase cAMP production by human osteosarcoma SaOS-2 cells. Another peak, KCMII, caused a dose-dependent increase in bone resorption, and a significant increase in medium calcium was noted at a 20-fold lower concentration (0.1 microgram protein/ml) than with KCMI. In contrast to KCMI, the increase in bone resorption stimulated by KCMII was accompanied by a parallel increase in the production of PGE2, and inhibition of PGE2 synthesis completely inhibited the bone resorption-stimulating activity of KCMII. KCMII also caused an increase in cAMP production by SaOS-2 cells. We conclude that KCM contains at least two distinct bone resorption-stimulating factors, one of which acts via a PG-mediated mechanism and the other by

  14. The Master Transcription Factor mtfA Governs Aflatoxin Production, Morphological Development and Pathogenicity in the Fungus Aspergillus flavus

    PubMed Central

    Zhuang, Zhenhong; Lohmar, Jessica M.; Satterlee, Timothy; Cary, Jeffrey W.; Calvo, Ana M.

    2016-01-01

    Aspergillus flavus produces a variety of toxic secondary metabolites; among them, the aflatoxins (AFs) are the most well known. These compounds are highly mutagenic and carcinogenic, particularly AFB1. A. flavus is capable of colonizing a number of economically-important crops, such as corn, cotton, peanut and tree nuts, and contaminating them with AFs. Molecular genetic studies in A. flavus could identify novel gene targets for use in strategies to reduce AF contamination and its adverse impact on food and feed supplies worldwide. In the current study, we investigated the role of the master transcription factor gene mtfA in A. flavus. Our results revealed that forced overexpression of mtfA results in a drastic decrease or elimination of several secondary metabolites, among them AFB1. The reduction in AFB1 was accompanied by a decrease in aflR expression. Furthermore, mtfA also regulates development; conidiation was influenced differently by this gene depending on the type of colonized substrate. In addition to its effect on conidiation, mtfA is necessary for the normal maturation of sclerotia. Importantly, mtfA positively affects the pathogenicity of A. flavus when colonizing peanut seeds. AF production in colonized seeds was decreased in the deletion mtfA strain and particularly in the overexpression strain, where only trace amounts were detected. Interestingly, a more rapid colonization of the seed tissue occurred when mtfA was overexpressed, coinciding with an increase in lipase activity and faster maceration of the oily part of the seed. PMID:26805883

  15. Reinventing Government.

    ERIC Educational Resources Information Center

    Osborne, David T.

    1993-01-01

    Throughout all levels of American government, a shift is taking place from the rigid, wasteful, centralized bureaucracies of the industrial era to the more flexible, entrepreneurial, decentralized government needed to succeed in today's world. This shift has been brought about by an unprecedented, ongoing fiscal crisis that has created a sudden…

  16. Remaking Governance.

    ERIC Educational Resources Information Center

    Carver, John

    2000-01-01

    The Policy Governance model's philosophical foundations lie in Rousseau's social contract, Greenleaf's servant-leadership, and modern management theory. Policy Governance stresses primacy of the owner-representative role; full-board authority; superintendents as chief executive officers; authoritative prescription of "ends," bounded freedom for…

  17. Policing Governance.

    ERIC Educational Resources Information Center

    Schuster, Jack H.

    1991-01-01

    The American Association of University Professors' (AAUP) new policy authorizing sanctions against colleges when investigation discloses serious departures from accepted governance norms is examined. Issues discussed include the existence and general relevance of governance norms, evidence of violation of those standards, and the AAUP's right to…

  18. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor.

    PubMed

    Haugen, Morten; Frederiksen, Jette L; Degn, Matilda

    2014-08-15

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells, helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death. In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13).

  19. Factors influencing the survival of outmigrating juvenile salmonids through multiple dam passages: an individual-based approach.

    PubMed

    Elder, Timothy; Woodley, Christa M; Weiland, Mark A; Strecker, Angela L

    2016-08-01

    Substantial declines of Pacific salmon populations have occurred over the past several decades related to large-scale anthropogenic and climatic changes in freshwater and marine environments. In the Columbia River Basin, migrating juvenile salmonids may pass as many as eight large-scale hydropower projects before reaching the ocean; however, the cumulative effects of multiple dam passages are largely unknown. Using acoustic transmitters and an extensive system of hydrophone arrays in the Lower Columbia River, we calculated the survival of yearling Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss) passing one, two, or three dams. We applied a unique index of biological characteristics and environmental exposures, experienced by each fish individually as it migrated downstream, in order to examine which factors most influence salmonid survival. High outflow volumes led to involuntary spill in 2011 and created an environment of supersaturated dissolved gas concentrations. In this environment, migrating smolt survival was strongly influenced by barometric pressure, fish velocity, and water temperature. The effect of these variables on survival was compounded by multiple dam passages compared to fish passing a single dam. Despite spatial isolation between dams in the Lower Columbia River hydrosystem, migrating smolt appear to experience cumulative effects akin to a press disturbance. In general, Chinook salmon and steelhead respond similarly in terms of survival rates and responses to altered environmental conditions. Management actions that limit dissolved gas concentrations in years of high flow will benefit migrating salmonids at this life stage. PMID:27547362

  20. Multiple human papillomavirus infections and HIV seropositivity as risk factors for abnormal cervical cytology among female sex workers in Nairobi.

    PubMed

    Patel, S J; Mugo, N R; Cohen, C R; Ting, J; Nguti, R; Kwatampora, J; Waweru, W; Patnaik, P; Donders, G G; Kimani, J; Kenney, D L; Kiviat, N B; Smith, J S

    2013-03-01

    We estimated type-specific prevalence of human papillomavirus (HPV) and examined risk factors for abnormal cervical cytology among 296 female sex workers from Nairobi, Kenya. Over half (54%) were infected with a high-risk (HR) HPV type, of which HPV16 and 52 were the most common types. HIV-1 prevalence was 23% and HIV-1 sero-positivity was associated with high-grade cervical lesions, particularly among women with CD4 count less than 500 cells/mm(3) (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 1.7-24.9). Among women who had normal cytology at the time of entry into the study, the risk of having an abnormal Pap smear within one year was significantly elevated for women with multiple HPV types at study entry (adjusted odds ratio [aOR] = 6.0; 95% CI: 2.3-15.7) and with a subset of HR HPV types (aOR = 4.2; 95% CI: 1.6-11.2). Detection of multiple concurrent HPV infections may be a useful marker to identify women at risk of developing precancerous lesions in populations of high HPV prevalence.

  1. Adaptation of a Counseling Intervention to Address Multiple Cancer Risk Factors Among Overweight/Obese Latino Smokers

    PubMed Central

    Castro, Yessenia; Fernández, Maria E.; Strong, Larkin L.; Stewart, Diana W.; Krasny, Sarah; Robles, Eden Hernandez; Heredia, Natalia; Spears, Claire A.; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W.

    2015-01-01

    More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social cognitive theory and principles of motivational interviewing originally developed for smoking cessation to also address physical activity and fruit/vegetable consumption among Latinos exhibiting multiple health risk behaviors. Literature reviews, focus groups, expert consultation, pretesting, and pilot testing were used to inform adaptation decisions. We identified common mechanisms underlying change in smoking, physical activity, and diet used as treatment targets; identified practical models of patient-centered cross-cultural service provision; and identified that family preferences and support as particularly strong concerns among the priority population. Adaptations made to the original intervention are described. The current study is a practical example of how an intervention can be adapted to maximize relevance and acceptability and also maintain the core elements of the original evidence-based intervention. The intervention has significant potential to influence cancer prevention efforts among Latinos in the United States and is being evaluated in a sample of 400 Latino overweight/obese smokers. PMID:25527143

  2. Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations

    PubMed Central

    Kristjansdottir, G; Sandling, J K; Bonetti, A; Roos, I M; Milani, L; Wang, C; Gustafsdottir, S M; Sigurdsson, S; Lundmark, A; Tienari, P J; Koivisto, K; Elovaara, I; Pirttilä, T; Reunanen, M; Peltonen, L; Saarela, J; Hillert, J; Olsson, T; Landegren, U; Alcina, A; Fernández, O; Leyva, L; Guerrero, M; Lucas, M; Izquierdo, G; Matesanz, F; Syvänen, A-C

    2008-01-01

    Background: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case–control cohorts from Spain and Sweden, and a set of MS trio families from Finland. Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases. PMID:18285424

  3. Sociocultural and Demographic Risk Factors for the Development of Multiple Sclerosis in Kuwait: A Case - Control Study

    PubMed Central

    Al-Shammri, Suhail N.; Hanna, Magdy G.; Chattopadhyay, Arpita; Akanji, Abayomi O.

    2015-01-01

    Introduction Immunological, genetic and environmental factors are believed to play important roles in the pathogenesis of Multiple Sclerosis (MS). There have been many studies on risk factors for MS but these have been mainly in Caucasian populations; robust studies in Arab populations remain relatively uncommon. This study therefore aimed to identify behavioral, socio-cultural, and demographic factors associated with development of MS in Kuwait, a high income Arab country, currently undergoing a demographic transition. Subjects and methods In this case- control study, 195 Kuwaiti MS patients and 146 healthy age and sex-matched controls were recruited. Both groups of subjects were interviewed using a structured questionnaire, in relation to anthropometric, socio-cultural and demographic data, residence during the 1990/91 Gulf War and current and past medical history, including medications. We also clinically evaluated, and retrospectively reviewed medical records of patients to derive appropriate clinical information, including associated chronic medical illness requiring long-term treatment. Results On multiple logistic regression analysis after adjustment for potential confounders including age, gender and BMI, in all the subjects, a positive associations prevail with presence of MS and some sociocultural and demographic factors, which included non-Bedouin ethnicity (AOR 2, 95% CI 1.0-3.9, p 0.049), positive family history of MS (AOR 10.6, 95% CI 3.0-36.9), p < 0.001), and low daily sunlight exposure of < 15min/day (AOR 5.3, 95% CI 2.7-10.5 p < 0.001). In addition, while 41.8% of MS patients indicated at least one comorbidity, only 26.8% of the controls reported any associated physical illness, with the suggestion that presence of certain comorbidities might increase MS risk (AOR 2.4, 95% CI 1.3-4.7, p < 0.001). Other risk variables such as smoking status and mode of routine outdoor dressing were not significant in all the MS subjects taken as a whole, but

  4. Patient-Identified Factors That Influence Spasticity in People with Stroke and Multiple Sclerosis Receiving Botulinum Toxin Injection Treatments

    PubMed Central

    Cheung, Janice; Rancourt, Amanda; Di Poce, Stephanie; Levine, Amy; Hoang, Jessica; Ismail, Farooq; Boulias, Chris

    2015-01-01

    ABSTRACT Purpose: To describe the nature, extent, and impact of spasticity; determine factors that are perceived to influence its severity; and examine the relationship between time since diagnosis and impact of spasticity on daily activities in people with stroke and multiple sclerosis (MS) who are receiving botulinum toxin injection treatments. Methods: After a cross-sectional telephone survey, descriptive statistics and correlations were analyzed separately for the stroke and MS groups. Results: A total of 29 people with stroke and 10 with MS were surveyed. Both groups perceived increased spasticity with outdoor cold (69% stroke, 60% MS), muscle fatigue (59% stroke, 80% MS), and mental stress (59% stroke, 90% MS). No statistically significant correlations were found between time since diagnosis and perceived impact of spasticity on function in the stroke (r=0.07, p=0.37) or MS (r=0.16, p=0.33) groups. The MS group experienced bilateral and more severe perception of spasticity in the legs than the stroke group and identified more factors as worsening their spasticity (p<0.05). Severity of leg (but not arm) spasticity was significantly correlated with severity of impact of the following factors in the MS group only: lying on the back (r=0.70, p<0.05), outdoor heat (r=0.61, p<0.05), and morning (r=0.59, p<0.05). Conclusion: Intrinsic and extrinsic triggers can influence the perception of spasticity differently depending on individual factors, severity, location (arm vs. leg), and distribution of spasticity (unilateral vs. bilateral). Clinicians can use the findings to better understand, educate, and treat people with stroke and MS. PMID:25931667

  5. Renewing governance.

    PubMed

    Loos, Gregory P

    2003-01-01

    Globalization's profound influence on social and political institutions need not be negative. Critics of globalization have often referred to the "Impossible Trinity" because decision-making must 1. respect national sovereignty, 2. develop and implement firm regulation, and 3. allow capital markets to be as free as possible. To many, such goals are mutually exclusive because history conditions us to view policy-making and governance in traditional molds. Thus, transnational governance merely appears impossible because current forms of governance were not designed to provide it. The world needs new tools for governing, and its citizens must seize the opportunity to help develop them. The rise of a global society requires a greater level of generality and inclusion than is found in most policy bodies today. Politicians need to re-examine key assumptions about government. States must develop ways to discharge their regulatory responsibilities across borders and collaborate with neighboring jurisdictions, multilateral bodies, and business. Concepts such as multilateralism and tripartism show great promise. Governments must engage civil society in the spirit of shared responsibility and democratic decision-making. Such changes will result in a renewal of the state's purpose and better use of international resources and expertise in governance. PMID:17208717

  6. Choosing the best treatment for multiple sclerosis: comparative effectiveness, safety, and other factors involved in disease-modifying therapy choice.

    PubMed

    Happe, Laura E

    2013-11-01

    Comparative effectiveness research (CER) has emerged as a priority for outlining the advantages and disadvantages of disease-modifying therapies (DMTs) for multiple sclerosis (MS). CER can provide physicians with valuable information to assist them in selecting the most appropriate therapeutics for their patients with MS. For payers, data from CER could inform decisions regarding the level of coverage for current and developing MS therapeutics, and drive the use of the most effective treatments for patients with MS. The base of CER data for DMTs has been expanding, and findings from a number of CER studies for currently available DMTs have been published, while further CER studies are planned to evaluate currently available and new DMTs or DMTs in development. While CER can be used to guide DMT selection for physicians and payers, the safety and tolerability of these treatments must be considered as well. Other emerging factors (eg, biomarkers and patient-specific factors) may also serve as important determinants of DMT choice in the future.

  7. Measuring bioconcentration factors in fish using exposure to multiple chemicals and internal benchmarking to correct for growth dilution.

    PubMed

    Adolfsson-Erici, Margaretha; Åkerman, Gun; McLachlan, Michael S

    2012-08-01

    Modern chemical legislation requires measuring the bioconcentration factor (BCF) of large numbers of chemicals in fish. The BCF must be corrected for growth dilution, because fish growth rates vary between laboratories. Two hypotheses were tested: (1) that BCFs of multiple chemicals can be measured simultaneously in one experiment, and (2) that internal benchmarking using a conservative test substance in the chemical mixture can be used to correct for growth dilution. Bioconcentration experiments were conducted following major elements of the OECD 305 guideline. Fish were simultaneously exposed to 11 chemicals selected to cover a range of BCFs and susceptibility to biotransformation. A method was developed to calculate the growth-corrected elimination rate constant from the concentration ratio of the analyte and a benchmarking chemical for which growth dilution dominated other elimination mechanisms. This method was applied to the experimental data using hexachlorobenzene as the benchmarking chemical. The growth dilution correction lowered the apparent elimination rate constants by between 5% and a factor of four for eight chemicals, while for two chemicals the growth-corrected elimination rate constant was not significantly different from zero. The benchmarking method reduced the uncertainty in the elimination rate constant compared to the existing method for growth dilution correction. The BCFs from exposing fish to 10 chemicals at once were consistent with BCF values from single-chemical exposures from the literature, supporting hypothesis 1.

  8. Prevalence of Antenatal Depression and Associated Risk Factors among Pregnant Women Attending Antenatal Clinics in Abeokuta North Local Government Area, Nigeria.

    PubMed

    Thompson, Okechukwu; Ajayi, IkeOluwapo

    2016-01-01

    Objective. The prevalence of antenatal depression (AD) and associated risk factors among pregnant women attending antenatal clinics in Abeokuta North Local Government Area, Nigeria, was determined. Methods. A descriptive cross-sectional survey was conducted, interviewing 314 pregnant women selected by multistage sampling technique from among those attending antenatal clinics. Information was collected using structured questionnaire and a screening tool, Edinburgh Postnatal Depression Scale (EPDS), to assess probable depression. Results. The prevalence of antenatal depression was 24.5%. There were significant associations between antenatal depression and attending public health facility (P = 0.000), young maternal age (P = 0.012), single marital status (P = 0.010), not having formal education (P = 0.022), large family size (P = 0.029), planned pregnancy (P = 0.014), coexisting medical conditions (P = 0.034), history of previous caesarian section (P = 0.032), drinking alcohol during pregnancy (P = 0.004), and gender based abuse (P = 0.001). On health seeking behaviour for antenatal depression among depressed pregnant women, most, 68.9%, consulted their husbands about their symptoms; 57.3% took the decision to get treatment from doctors, and 52% sought prayer in the church. Conclusion. Antenatal depression is prevalent in this study population. Interventions to address its risk factors should be carried out and physicians should suspect depression in pregnant women reporting alcohol use and gender abuse. PMID:27635258

  9. Prevalence of Antenatal Depression and Associated Risk Factors among Pregnant Women Attending Antenatal Clinics in Abeokuta North Local Government Area, Nigeria

    PubMed Central

    Ajayi, IkeOluwapo

    2016-01-01

    Objective. The prevalence of antenatal depression (AD) and associated risk factors among pregnant women attending antenatal clinics in Abeokuta North Local Government Area, Nigeria, was determined. Methods. A descriptive cross-sectional survey was conducted, interviewing 314 pregnant women selected by multistage sampling technique from among those attending antenatal clinics. Information was collected using structured questionnaire and a screening tool, Edinburgh Postnatal Depression Scale (EPDS), to assess probable depression. Results. The prevalence of antenatal depression was 24.5%. There were significant associations between antenatal depression and attending public health facility (P = 0.000), young maternal age (P = 0.012), single marital status (P = 0.010), not having formal education (P = 0.022), large family size (P = 0.029), planned pregnancy (P = 0.014), coexisting medical conditions (P = 0.034), history of previous caesarian section (P = 0.032), drinking alcohol during pregnancy (P = 0.004), and gender based abuse (P = 0.001). On health seeking behaviour for antenatal depression among depressed pregnant women, most, 68.9%, consulted their husbands about their symptoms; 57.3% took the decision to get treatment from doctors, and 52% sought prayer in the church. Conclusion. Antenatal depression is prevalent in this study population. Interventions to address its risk factors should be carried out and physicians should suspect depression in pregnant women reporting alcohol use and gender abuse.

  10. Prevalence of Antenatal Depression and Associated Risk Factors among Pregnant Women Attending Antenatal Clinics in Abeokuta North Local Government Area, Nigeria.

    PubMed

    Thompson, Okechukwu; Ajayi, IkeOluwapo

    2016-01-01

    Objective. The prevalence of antenatal depression (AD) and associated risk factors among pregnant women attending antenatal clinics in Abeokuta North Local Government Area, Nigeria, was determined. Methods. A descriptive cross-sectional survey was conducted, interviewing 314 pregnant women selected by multistage sampling technique from among those attending antenatal clinics. Information was collected using structured questionnaire and a screening tool, Edinburgh Postnatal Depression Scale (EPDS), to assess probable depression. Results. The prevalence of antenatal depression was 24.5%. There were significant associations between antenatal depression and attending public health facility (P = 0.000), young maternal age (P = 0.012), single marital status (P = 0.010), not having formal education (P = 0.022), large family size (P = 0.029), planned pregnancy (P = 0.014), coexisting medical conditions (P = 0.034), history of previous caesarian section (P = 0.032), drinking alcohol during pregnancy (P = 0.004), and gender based abuse (P = 0.001). On health seeking behaviour for antenatal depression among depressed pregnant women, most, 68.9%, consulted their husbands about their symptoms; 57.3% took the decision to get treatment from doctors, and 52% sought prayer in the church. Conclusion. Antenatal depression is prevalent in this study population. Interventions to address its risk factors should be carried out and physicians should suspect depression in pregnant women reporting alcohol use and gender abuse.

  11. Prevalence of Antenatal Depression and Associated Risk Factors among Pregnant Women Attending Antenatal Clinics in Abeokuta North Local Government Area, Nigeria

    PubMed Central

    Ajayi, IkeOluwapo

    2016-01-01

    Objective. The prevalence of antenatal depression (AD) and associated risk factors among pregnant women attending antenatal clinics in Abeokuta North Local Government Area, Nigeria, was determined. Methods. A descriptive cross-sectional survey was conducted, interviewing 314 pregnant women selected by multistage sampling technique from among those attending antenatal clinics. Information was collected using structured questionnaire and a screening tool, Edinburgh Postnatal Depression Scale (EPDS), to assess probable depression. Results. The prevalence of antenatal depression was 24.5%. There were significant associations between antenatal depression and attending public health facility (P = 0.000), young maternal age (P = 0.012), single marital status (P = 0.010), not having formal education (P = 0.022), large family size (P = 0.029), planned pregnancy (P = 0.014), coexisting medical conditions (P = 0.034), history of previous caesarian section (P = 0.032), drinking alcohol during pregnancy (P = 0.004), and gender based abuse (P = 0.001). On health seeking behaviour for antenatal depression among depressed pregnant women, most, 68.9%, consulted their husbands about their symptoms; 57.3% took the decision to get treatment from doctors, and 52% sought prayer in the church. Conclusion. Antenatal depression is prevalent in this study population. Interventions to address its risk factors should be carried out and physicians should suspect depression in pregnant women reporting alcohol use and gender abuse. PMID:27635258

  12. Understanding Horizontal Governance. Research Brief

    ERIC Educational Resources Information Center

    Ferguson, Daniel

    2009-01-01

    Horizontal governance is an umbrella term that covers a range of approaches to policy development, service delivery issues, and management practices. A horizontal initiative may take place across levels of government, across boundaries between units of a single department or agency or among multiple departments or agencies, or across public,…

  13. Prediction of the processing factor for pesticides in apple juice by principal component analysis and multiple linear regression.

    PubMed

    Martin, L; Mezcua, M; Ferrer, C; Gil Garcia, M D; Malato, O; Fernandez-Alba, A R

    2013-01-01

    The main objective of this work was to establish a mathematical function that correlates pesticide residue levels in apple juice with the levels of the pesticides applied on the raw fruit, taking into account some of their physicochemical properties such as water solubility, the octanol/water partition coefficient, the organic carbon partition coefficient, vapour pressure and density. A mixture of 12 pesticides was applied to an apple tree; apples were collected after 10 days of application. After harvest, apples were treated with a mixture of three post-harvest pesticides and the fruits were then processed in order to obtain apple juice following a routine industrial process. The pesticide residue levels in the apple samples were analysed using two multi-residue methods based on LC-MS/MS and GC-MS/MS. The concentration of pesticides was determined in samples derived from the different steps of processing. The processing factors (the coefficient between residue level in the processed commodity and the residue level in the commodity to be processed) obtained for the full juicing process were found to vary among the different pesticides studied. In order to investigate the relationships between the levels of pesticide residue found in apple juice samples and their physicochemical properties, principal component analysis (PCA) was performed using two sets of samples (one of them using experimental data obtained in this work and the other including the data taken from the literature). In both cases the correlation was found between processing factors of pesticides in the apple juice and the negative logarithms (base 10) of the water solubility, octanol/water partition coefficient and organic carbon partition coefficient. The linear correlation between these physicochemical properties and the processing factor were established using a multiple linear regression technique.

  14. MicroRNA miR-8 regulates multiple growth factor hormones produced from Drosophila fat cells.

    PubMed

    Lee, G J; Jun, J W; Hyun, S

    2015-06-01

    Metabolic organs such as the liver and adipose tissue produce several peptide hormones that influence metabolic homeostasis. Fat bodies, the Drosophila counterpart of liver and adipose tissues, have been thought to analogously secrete several hormones that affect organismal physiology, but their identity and regulation remain poorly understood. Previous studies have indicated that microRNA miR-8, functions in the fat body to non-autonomously regulate organismal growth, suggesting that fat body-derived humoral factors are regulated by miR-8. Here, we found that several putative peptide hormones known to have mitogenic effects are regulated by miR-8 in the fat body. Most members of the imaginal disc growth factors and two members of the adenosine deaminase-related growth factors are up-regulated in the absence of miR-8. Drosophila insulin-like peptide 6 (Dilp6) and imaginal morphogenesis protein-late 2 (Imp-L2), a binding partner of Dilp, are also up-regulated in the fat body of miR-8 null mutant larvae. The fat body-specific reintroduction of miR-8 into the miR-8 null mutants revealed six peptides that showed fat-body organ-autonomous regulation by miR-8. Amongst them, only Imp-L2 was found to be regulated by U-shaped, the miR-8 target for body growth. However, a rescue experiment by knockdown of Imp-L2 indicated that Imp-L2 alone does not account for miR-8's control over the insect's growth. Our findings suggest that multiple peptide hormones regulated by miR-8 in the fat body may collectively contribute to Drosophila growth.

  15. Continuum of Care in a Maternal, Newborn and Child Health Program in Ghana: Low Completion Rate and Multiple Obstacle Factors

    PubMed Central

    Yeji, Francis; Shibanuma, Akira; Oduro, Abraham; Debpuur, Cornelius; Kikuchi, Kimiyo; Owusu-Agei, Seth; Gyapong, Margaret; Okawa, Sumiyo; Ansah, Evelyn; Asare, Gloria Quansah; Nanishi, Keiko; Williams, John; Addei, Sheila; Tawiah, Charlotte; Yasuoka, Junko; Enuameh, Yeetey; Sakeah, Evelyn; Wontuo, Peter; Jimba, Masamine; Hodgson, Abraham

    2015-01-01

    Background Slow progress has been made in achieving the Millennium Development Goals 4 and 5 in Ghana. Ensuring continuum of care (at least four antenatal visits; skilled birth attendance; postnatal care within 48 hours, at two weeks, and six weeks) for mother and newborn is crucial in helping Ghana achieve these goals and beyond. This study examined the levels and factors associated with continuum of care (CoC) completion among Ghanaian women aged 15–49. Methods A retrospective cross-sectional survey was conducted among women who experienced live births between January 2011 and April 2013 in three regions of Ghana. In a two-stage random sampling method, 1,500 women with infants were selected and interviewed about maternal and newborn service usage in line with CoC. Multiple logistic regression models were used to assess factors associated with CoC completion. Results Only 8.0% had CoC completion; the greatest gap and contributor to the low CoC was detected between delivery and postnatal care within 48 hours postpartum. About 95% of women had a minimum of four antenatal visits and postnatal care at six weeks postpartum. A total of 75% had skilled assisted delivery and 25% received postnatal care within 48 hours. Factors associated with CoC completion at 95% CI were geographical location (OR = 0.35, CI 0.13–0.39), marital status (OR = 0.45; CI 0.22–0.95), education (OR = 2.71; CI 1.11–6.57), transportation (OR = 1.97; CI 1.07–3.62), and beliefs about childhood illnesses (OR = 0.34; CI0.21–0.61). Conclusion The continuum of care completion rate is low in the study site. Efforts should focus on increasing postnatal care within 48 hours and overcoming the known obstacles to increasing the continuum of care completion rate. PMID:26650388

  16. Identification of key factors governing chemistry in groundwater near the water course recharged by reclaimed water at Miyun County, Northern China.

    PubMed

    Yu, Yilei; Song, Xianfang; Zhang, Yinghua; Zheng, Fandong; Liang, Ji; Han, Dongmei; Ma, Ying; Bu, Hongmei

    2013-09-01

    Reclaimed water was successfully used to recover the dry Chaobai River in Northern China, but groundwater may be polluted. To ensure groundwater protection, it is therefore critical to identify the governing factors of groundwater chemistry. Samples of reclaimed water, river and groundwater were collected monthly at Chaobai River from January to September in 2010. Fifteen water parameters were analyzed. Two kinds of reclaimed water were different in type (Na-Ca-Mg-Cl-HCO3 or Na-Ca-Cl-HCO3) and concentration of nitrogen. The ionic concentration and type in river were similar to reclaimed water. Some shallow wells near the river bed had the same type (Na-Ca-Mg-Cl-HCO3) and high concentration as reclaimed water, but others were consistent with the deep wells (Ca-Mg-HCO3). Using cluster analysis, the 9 months were divided into two periods (dry and wet seasons), and all samples were grouped into several spatial clusters, indicating different controlling mechanisms. Principal component analysis and conventional ionic plots showed that calcium, magnesium and bicarbonate were controlled by water-rock interaction in all deep and some shallow wells. This included the dissolution of calcite and carbonate weathering. Sodium, potassium, chloride and sulfate in river and some shallow wells recharged by river were governed by evaporation crystallization and mixing of reclaimed water. But groundwater chemistry was not controlled by precipitation. During the infiltration of reclaimed water, cation exchange took place between (sodium, potassium) and (calcium, magnesium). Nitrification and denitrification both happened in most shallow groundwater, but only denitrification in deep groundwater. PMID:24520717

  17. Identification of key factors governing chemistry in groundwater near the water course recharged by reclaimed water at Miyun County, Northern China.

    PubMed

    Yu, Yilei; Song, Xianfang; Zhang, Yinghua; Zheng, Fandong; Liang, Ji; Han, Dongmei; Ma, Ying; Bu, Hongmei

    2013-09-01

    Reclaimed water was successfully used to recover the dry Chaobai River in Northern China, but groundwater may be polluted. To ensure groundwater protection, it is therefore critical to identify the governing factors of groundwater chemistry. Samples of reclaimed water, river and groundwater were collected monthly at Chaobai River from January to September in 2010. Fifteen water parameters were analyzed. Two kinds of reclaimed water were different in type (Na-Ca-Mg-Cl-HCO3 or Na-Ca-Cl-HCO3) and concentration of nitrogen. The ionic concentration and type in river were similar to reclaimed water. Some shallow wells near the river bed had the same type (Na-Ca-Mg-Cl-HCO3) and high concentration as reclaimed water, but others were consistent with the deep wells (Ca-Mg-HCO3). Using cluster analysis, the 9 months were divided into two periods (dry and wet seasons), and all samples were grouped into several spatial clusters, indicating different controlling mechanisms. Principal component analysis and conventional ionic plots showed that calcium, magnesium and bicarbonate were controlled by water-rock interaction in all deep and some shallow wells. This included the dissolution of calcite and carbonate weathering. Sodium, potassium, chloride and sulfate in river and some shallow wells recharged by river were governed by evaporation crystallization and mixing of reclaimed water. But groundwater chemistry was not controlled by precipitation. During the infiltration of reclaimed water, cation exchange took place between (sodium, potassium) and (calcium, magnesium). Nitrification and denitrification both happened in most shallow groundwater, but only denitrification in deep groundwater.

  18. Plasticity in above- and belowground resource acquisition traits in response to single and multiple environmental factors in three tree species.

    PubMed

    Freschet, Grégoire T; Bellingham, Peter J; Lyver, Philip O'B; Bonner, Karen I; Wardle, David A

    2013-04-01

    Functional trait plasticity is a major component of plant adjustment to environmental stresses. Here, we explore how multiple local environmental gradients in resources required by plants (light, water, and nutrients) and soil disturbance together influence the direction and amplitude of intraspecific changes in leaf and fine root traits that facilitate capture of these resources. We measured population-level analogous above- and belowground traits related to resource acquisition, i.e. "specific leaf area"-"specific root length" (SLA-SRL), and leaf and root N, P, and dry matter content (DMC), on three dominant understory tree species with contrasting carbon and nutrient economics across 15 plots in a temperate forest influenced by burrowing seabirds. We observed similar responses of the three species to the same single environmental influences, but partially species-specific responses to combinations of influences. The strength of intraspecific above- and belowground trait responses appeared unrelated to species resource acquisition strategy. Finally, most analogous leaf and root traits (SLA vs. SRL, and leaf versus root P and DMC) were controlled by contrasting environmental influences. The decoupled responses of above- and belowground traits to these multiple environmental factors together with partially species-specific adjustments suggest complex responses of plant communities to environmental changes, and potentially contrasting feedbacks of plant traits with ecosystem properties. We demonstrate that despite the growing evidence for broadly consistent resource-acquisition strategies at the whole plant level among species, plants also show partially decoupled, finely tuned strategies between above- and belowground parts at the intraspecific level in response to their environment. This decoupling within species suggests a need for many species-centred ecological theories on how plants respond to their environments (e.g. competitive/stress-tolerant/ruderal and

  19. Vascular endothelial growth factor A: just one of multiple mechanisms for sex-specific vascular development within the testis?

    PubMed

    Sargent, Kevin M; McFee, Renee M; Spuri Gomes, Renata; Cupp, Andrea S

    2015-11-01

    Testis development from an indifferent gonad is a critical step in embryogenesis. A hallmark of testis differentiation is sex-specific vascularization that occurs as endothelial cells migrate from the adjacent mesonephros into the testis to surround Sertoli-germ cell aggregates and induce seminiferous cord formation. Many in vitro experiments have demonstrated that vascular endothelial growth factor A (VEGFA) is a critical regulator of this process. Both inhibitors to VEGFA signal transduction and excess VEGFA isoforms in testis organ cultures impaired vascular development and seminiferous cord formation. However, in vivo models using mice which selectively eliminated all VEGFA isoforms: in Sertoli and germ cells (pDmrt1-Cre;Vegfa(-/-)); Sertoli and Leydig cells (Amhr2-Cre;Vegfa(-/-)) or Sertoli cells (Amh-Cre;Vegfa(-/-) and Sry-Cre;Vegfa(-/-)) displayed testes with observably normal cords and vasculature at postnatal day 0 and onwards. Embryonic testis development may be delayed in these mice; however, the postnatal data indicate that VEGFA isoforms secreted from Sertoli, Leydig or germ cells are not required for testis morphogenesis within the mouse. A Vegfa signal transduction array was employed on postnatal testes from Sry-Cre;Vegfa(-/-) versus controls. Ptgs1 (Cox1) was the only upregulated gene (fivefold). COX1 stimulates angiogenesis and upregulates, VEGFA, Prostaglandin E2 (PGE2) and PGD2. Thus, other gene pathways may compensate for VEGFA loss, similar to multiple independent mechanisms to maintain SOX9 expression. Multiple independent mechanism that induce vascular development in the testis may contribute to and safeguard the sex-specific vasculature development responsible for inducing seminiferous cord formation, thus ensuring appropriate testis morphogenesis in the male.

  20. Plasticity in above- and belowground resource acquisition traits in response to single and multiple environmental factors in three tree species

    PubMed Central

    Freschet, Grégoire T; Bellingham, Peter J; Lyver, Philip O'B; Bonner, Karen I; Wardle, David A

    2013-01-01

    Functional trait plasticity is a major component of plant adjustment to environmental stresses. Here, we explore how multiple local environmental gradients in resources required by plants (light, water, and nutrients) and soil disturbance together influence the direction and amplitude of intraspecific changes in leaf and fine root traits that facilitate capture of these resources. We measured population-level analogous above- and belowground traits related to resource acquisition, i.e. “specific leaf area”–“specific root length” (SLA–SRL), and leaf and root N, P, and dry matter content (DMC), on three dominant understory tree species with contrasting carbon and nutrient economics across 15 plots in a temperate forest influenced by burrowing seabirds. We observed similar responses of the three species to the same single environmental influences, but partially species-specific responses to combinations of influences. The strength of intraspecific above- and belowground trait responses appeared unrelated to species resource acquisition strategy. Finally, most analogous leaf and root traits (SLA vs. SRL, and leaf versus root P and DMC) were controlled by contrasting environmental influences. The decoupled responses of above- and belowground traits to these multiple environmental factors together with partially species-specific adjustments suggest complex responses of plant communities to environmental changes, and potentially contrasting feedbacks of plant traits with ecosystem properties. We demonstrate that despite the growing evidence for broadly consistent resource-acquisition strategies at the whole plant level among species, plants also show partially decoupled, finely tuned strategies between above- and belowground parts at the intraspecific level in response to their environment. This decoupling within species suggests a need for many species-centred ecological theories on how plants respond to their environments (e.g. competitive

  1. Classification and Clustering Methods for Multiple Environmental Factors in Gene-Environment Interaction: Application to the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Ko, Yi-An; Mukherjee, Bhramar; Smith, Jennifer A; Kardia, Sharon L R; Allison, Matthew; Diez Roux, Ana V

    2016-11-01

    There has been an increased interest in identifying gene-environment interaction (G × E) in the context of multiple environmental exposures. Most G × E studies analyze one exposure at a time, but we are exposed to multiple exposures in reality. Efficient analysis strategies for complex G × E with multiple environmental factors in a single model are still lacking. Using the data from the Multiethnic Study of Atherosclerosis, we illustrate a two-step approach for modeling G × E with multiple environmental factors. First, we utilize common clustering and classification strategies (e.g., k-means, latent class analysis, classification and regression trees, Bayesian clustering using Dirichlet Process) to define subgroups corresponding to distinct environmental exposure profiles. Second, we illustrate the use of an additive main effects and multiplicative interaction model, instead of the conventional saturated interaction model using product terms of factors, to study G × E with the data-driven exposure subgroups defined in the first step. We demonstrate useful analytical approaches to translate multiple environmental exposures into one summary class. These tools not only allow researchers to consider several environmental exposures in G × E analysis but also provide some insight into how genes modify the effect of a comprehensive exposure profile instead of examining effect modification for each exposure in isolation.

  2. Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study

    PubMed Central

    Ehling, Rainer; Lutterotti, Andreas; Hegen, Harald; Di Pauli, Franziska; Auer, Michael; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

    2016-01-01

    Background Multiple sclerosis (MS) has a highly heterogenic course making prediction of long term outcome very difficult. Objective The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset. Methods This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5), moderate (EDSS 3.0–5.5) or severe (EDSS ≥6.0) disability were calculated to correct for confounders. Results Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0–1580.1); p<0.001). Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23–0.77; p = 0.005), while depression (HR 3.59; CI 1.14–11.24; p = 0.028) and cognitive dysfunction (HR 4.64; CI 1.11–19.50; p = 0.036) 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability. Conclusion We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms. PMID:27391947

  3. The effect of a joint communication campaign on multiple sex partners in Mozambique: the role of psychosocial/ideational factors.

    PubMed

    Figueroa, Maria Elena; Kincaid, D Lawrence; Hurley, Emily A

    2014-01-01

    Mozambique is one of the countries in sub-Saharan Africa most affected by the HIV epidemic. Multiple and concurrent sexual partnerships (MSP/CP) have been recognized as one of the key drivers in the rapid spread of HIV in the region. Though HIV prevention programs have been successful in increasing condom use and HIV testing, reducing the practice of MSP/CP has been more difficult. Grounding their interventions in social and behavior change theory, four organizations in Mozambique joined efforts to implement a year-long, multimedia national campaign for HIV prevention with emphasis on the reduction of MSP/CP. Evaluating its impact and identifying the factors that hinder or contribute to its success are critical to building effective programs in the future. With data from a 2011 population-based survey of 1427 sexually active women and men, multivariate causal attribution (MCA) analysis was used to estimate the impact of the campaign in the four regions of Mozambique with the highest levels of HIV prevalence. The analysis tested the psychosocial pathways through which the campaign was expected to affect MSP. The results indicate that exposure (recall) was high; 81.2% of the respondents could recall one or more of the communication campaign components. The campaign had a significant indirect impact on MSP through its negative effect on attitudes that favor MSP, and its positive effect on knowledge and discussion of MSP risk with sex partner. This study demonstrates the value of identifying appropriate psychosocial factors and using them to design the campaign communication strategy, and evaluate the causal pathways by which it has an impact. The campaign was successful in changing MSP behavior by working through two psychosocial variables.

  4. Government Regulatory

    NASA Astrophysics Data System (ADS)

    Becker, Katie

    Government regulation of food products, food processing, and food preparation is imperative in bringing an unadulterated, nonmisleading, and safe food product to market and is relevant to all areas of food science, including engineering, processing, chemistry, and microbiology. The liability associated with providing consumers with an adulterated or substandard product cannot only tarnish a company's name and reputation, but also impose substantial financial repercussions on the company and those individuals who play an active role in the violation. In order for a company to fully comply with the relevant food laws (both federal and state), an intimate knowledge of food science is required. Individuals knowledgeable in food science play an integral role not only in implementing and counseling food companies/processors to ensure compliance with government regulations, but these individuals are also necessary to the state and federal governments that make and enforce the relevant laws and regulators.

  5. A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation

    PubMed Central

    Ruehle, Marisa D; Zhang, Haibo; Sheridan, Ryan M; Mitra, Somdeb; Chen, Yuanwei; Gonzalez, Ruben L; Cooperman, Barry S; Kieft, Jeffrey S

    2015-01-01

    Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs. DOI: http://dx.doi.org/10.7554/eLife.08146.001 PMID:26523395

  6. The Three Sisters of Fate in Multiple Sclerosis: Klotho (Clotho), Fibroblast Growth Factor-23 (Lachesis), and Vitamin D (Atropos)

    PubMed Central

    Ellidag, Hamit Yasar; Yilmaz, Necat; Kurtulus, Fatma; Aydin, Ozgur; Eren, Esin; Inci, Ayca; Dolu, Suleyman; Ince, Fatma Demet Arslan; Giray, Özlem; Yaman, Aylin

    2016-01-01

    Background The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP). Purpose This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients. Methods Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38.3 years) and 31 age-sex matched healthy controls (12 males and 19 females; median age 38.5 years) were included in this study. All patients were diagnosed with MS according to the criteria of McDonald. Results Serum sKlt, FGF-23, and P levels were significantly higher in MS patients compared to the control group (p < 0.01, p < 0.01, and p = 0.02, respectively). Serum 25-(OH)-vitamin D and Ca levels were significantly lower in MS patients (p < 0.01 and p = 0.04, respectively). Conclusion Klt, which is secreted from CP, could be a response to the inflammatory condition in MS. Elevated FGF-23 levels suppress 1α-hydroxylase and upregulates 24α-hydroxylase, which results in a decrease in 1,25-(OH)2D3 levels. Thus, the neuroprotective and immunomodulatory effects of vitamin D might not be seen in MS patients. PMID:27721584

  7. Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor.

    PubMed

    Varma Penmetsa, R; Carrasquilla-Garcia, Noelia; Bergmann, Emily M; Vance, Lisa; Castro, Brenna; Kassa, Mulualem T; Sarma, Birinchi K; Datta, Subhojit; Farmer, Andrew D; Baek, Jong-Min; Coyne, Clarice J; Varshney, Rajeev K; von Wettberg, Eric J B; Cook, Douglas R

    2016-09-01

    Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea's B locus that conditions flower and seed colors, orthologous to Mendel's A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea.

  8. Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma.

    PubMed

    Kuhn, Deborah J; Berkova, Zuzana; Jones, Richard J; Woessner, Richard; Bjorklund, Chad C; Ma, Wencai; Davis, R Eric; Lin, Pei; Wang, Hua; Madden, Timothy L; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Wang, Michael; Thomas, Sheeba K; Shah, Jatin J; Weber, Donna M; Orlowski, Robert Z

    2012-10-18

    Proteasome inhibition with bortezomib is a validated approach to the treatment of multiple myeloma, but drug resistance often emerges and limits its utility in the retreatment setting. To begin to identify some of the mechanisms involved, we developed bortezomib-resistant myeloma cell lines that, unlike previously reported models, showed no β5 subunit mutations. Instead, up-regulation of the insulin-like growth factor (IGF)-1 axis was identified, with increased autocrine and paracrine secretion of IGF-1, leading to increased activation of the IGF-1 receptor (IGF-1R). Exogenous IGF-1 reduced cellular sensitivity to bortezomib, whereas pharmacologic or small hairpin RNA-mediated IGF-1R suppression enhanced bortezomib sensitivity in cell lines and patient samples. In vitro studies with OSI-906, a clinically relevant dual IGF-1R and insulin receptor inhibitor, showed it acted synergistically with bortezomib, and potently resensitized bortezomib-resistant cell lines and patient samples to bortezomib. Importantly, OSI-906 in combination with bortezomib also overcame bortezomib resistance in an in vivo model of myeloma. Taken together, these data support the hypothesis that signaling through the IGF-1/IGF-1R axis contributes to acquired bortezomib resistance, and provide a rationale for combining bortezomib with IGF-1R inhibitors like OSI-906 to overcome or possibly prevent the emergence of bortezomib-refractory disease in the clinic. PMID:22932796

  9. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures.

    PubMed

    Kaufman, Brett A; Durisic, Nela; Mativetsky, Jeffrey M; Costantino, Santiago; Hancock, Mark A; Grutter, Peter; Shoubridge, Eric A

    2007-09-01

    Packaging DNA into condensed structures is integral to the transmission of genomes. The mammalian mitochondrial genome (mtDNA) is a high copy, maternally inherited genome in which mutations cause a variety of multisystem disorders. In all eukaryotic cells, multiple mtDNAs are packaged with protein into spheroid bodies called nucleoids, which are the fundamental units of mtDNA segregation. The mechanism of nucleoid formation, however, remains unknown. Here, we show that the mitochondrial transcription factor TFAM, an abundant and highly conserved High Mobility Group box protein, binds DNA cooperatively with nanomolar affinity as a homodimer and that it is capable of coordinating and fully compacting several DNA molecules together to form spheroid structures. We use noncontact atomic force microscopy, which achieves near cryo-electron microscope resolution, to reveal the structural details of protein-DNA compaction intermediates. The formation of these complexes involves the bending of the DNA backbone, and DNA loop formation, followed by the filling in of proximal available DNA sites until the DNA is compacted. These results indicate that TFAM alone is sufficient to organize mitochondrial chromatin and provide a mechanism for nucleoid formation.

  10. More than just one: multiplicity of Hirudins and Hirudin-like Factors in the Medicinal Leech, Hirudo medicinalis.

    PubMed

    Müller, Christian; Mescke, Katharina; Liebig, Stephanie; Mahfoud, Hala; Lemke, Sarah; Hildebrandt, Jan-Peter

    2016-02-01

    Blood-sucking leeches like the medicinal leech, Hirudo medicinalis, have been used for medical purposes since ancient times. During feeding, medicinal leeches transfer a broad range of bioactive substances into the host's wound to prevent premature hemostasis and blood coagulation. Hirudin is probably the best known of these substances. Despite its long history of investigation, recombinant production and clinical use, there still exist conflicting data regarding the primary structure of hirudin. Entirely unclear is the potential biological significance of three different subtypes and many isoforms of hirudins that have been characterized so far. Furthermore, there is only incomplete information on their cDNA sequences and no information at all on gene structures and DNA sequences are available in the databases. Our efforts to fill these gaps revealed the presence of multiple hirudin-encoding genes in the genome of Hirudo medicinalis. We have strong evidence for the expression of all three subtypes of hirudin within individual leeches and for the expression of additional hirudins or hirudin-like factors that may have different biological functions and may be promising candidates for new drugs.

  11. Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor.

    PubMed

    Varma Penmetsa, R; Carrasquilla-Garcia, Noelia; Bergmann, Emily M; Vance, Lisa; Castro, Brenna; Kassa, Mulualem T; Sarma, Birinchi K; Datta, Subhojit; Farmer, Andrew D; Baek, Jong-Min; Coyne, Clarice J; Varshney, Rajeev K; von Wettberg, Eric J B; Cook, Douglas R

    2016-09-01

    Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea's B locus that conditions flower and seed colors, orthologous to Mendel's A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea. PMID:27193699

  12. The town of Cabar, Croatia, a high risk area for multiple sclerosis--analytic epidemiology of dietary factors.

    PubMed

    Perković, Olivio; Jurjević, Ante; Rudez, Josip; Antoncić, Igor; Bralić, Marina; Kapović, Miljenko

    2010-04-01

    Multiple sclerosis (MS) is demyelization disease of central nervous system of unidentified causes. Analytic epidemiological research of 19 patients, clinically approved cases of MS and 25 controls, autochthonic inhabitants of town of Cabar, Croatia, the high-risk zone for the disease, was made. The research plan included case-control investigation--the "door to door" questionnaire--about nutrition habits. An odds ratio (OR) was calculated for all the factors which were more frequently found in the patients than in the controls, and vice versa. The variables that were connected with significant risk for MS in the town of Cabar included: alcohol consumption (p = 0.05), animal fats/dried meat products consumption (p = 0.007), nitrate salting (p = 0.03), strong spices (p = 0.007), mixed bread (p = 0.002), oat and oat products consumption (p = 0.0075). No connection was found with regular consumption of vegetables and fruit (p = 0.009), blue fresh fish (p = 0.028), other fresh fish (p = 0.03), freshwater fish (p = 0.002), canned fish (p = 0.004), dormouse meat (p = 0.007), air-dried meat products (p = 0.004) and using the water from water supply (p = 0.011). In the town of Cabar nutritional customs, primarily food rich in animal fats, alcohol-abuse, and oat consumption could have an influence on MS pathogenesis in genetically inclined individuals.

  13. MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth by integrating multiple hormonal pathways.

    PubMed

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Obata, Toshihiro; Fernie, Alisdair R; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2013-10-01

    Growth regulation is an important aspect of plant adaptation during environmental perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB transcription factor of rice, was explored. OsMPS is induced by salt stress and expressed in vegetative and reproductive tissues. Over-expression of OsMPS reduces growth under non-stress conditions, while knockdown plants display increased biomass. OsMPS expression is induced by abscisic acid and cytokinin, but is repressed by auxin, gibberellin and brassinolide. Growth retardation caused by OsMPS over-expression is partially restored by auxin application. Expression profiling revealed that OsMPS negatively regulates the expression of EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling genes. Furthermore, the expression of OsMPS-dependent genes is regulated by auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its target genes to various hormones suggest an integrative function of OsMPS in the cross-talk between phytohormones and the environment to regulate adaptive growth.

  14. Determination of the multiplication factor and its bias by the {sup 252}Cf-source technique: A method for code benchmarking with subcritical configurations

    SciTech Connect

    Perez, R.B.; Valentine, T.E.; Mihalczo, J.T.; Mattingly, J.K.

    1997-08-01

    A brief discussion of the Cf-252 source driven method for subcritical measurements serves as an introduction to the concept and use of the spectral ratio, {Gamma}. It has also been shown that the Monte Carlo calculation of spectral densities and effective multiplication factors have as a common denominator the transport propagator. This commonality follows from the fact that the Neumann series expansion of the propagator lends itself to the Monte Carlo method. On this basis a linear relationship between the spectral ratio and the effective multiplication factor has been shown. This relationship demonstrates the ability of subcritical measurements of the ratio of spectral densities to validate transport theory methods and cross sections.

  15. Single-molecule studies of the stringency factors and rates governing the polymerization of RecA on double-stranded DNA

    PubMed Central

    Feinstein, Efraim; Danilowicz, Claudia; Conover, Alyson; Gunaratne, Ruwan; Kleckner, Nancy; Prentiss, Mara

    2011-01-01

    RecA is a key protein in homologous recombination. During recombination, one single-stranded DNA (ssDNA) bound to site I in RecA exchanges Watson–Crick pairing with a sequence-matched ssDNA that was part of a double-stranded DNA molecule (dsDNA) bound to site II in RecA. After strand exchange, heteroduplex dsDNA is bound to site I. In vivo, direct polymerization of RecA on dsDNA through site I does not occur, though it does in vitro. The mechanisms underlying the difference have been unclear. We use single-molecule experiments to decouple the two steps involved in polymerization: nucleation and elongation. We find that elongation is governed by a fundamental clock that is insensitive to force and RecA concentration from 0.2 and 6 µM, though rates depend on ionic conditions. Thus, we can probe nucleation site stability by creating nucleation sites at high force and then measuring elongation as a function of applied force. We find that in the presence of ATP hydrolysis a minimum force is required for polymerization. The minimum force decreases with increasing RecA or ATP concentrations. We propose that force reduces the off-rate for nucleation site binding and that nucleation site stability is the stringency factor that prevents in vivo polymerization. PMID:21245047

  16. A comparative study of factors influencing decisions on desired family size among married men and women in Bokkos, a rural local government area in Plateau state.

    PubMed

    Kahansim, Makshwar L; Hadejia, Idris S; Sambo, Mohammed N

    2013-03-01

    The total fertility rate of Nigerian women has remained high at 5.7. This is even higher for women in rural areas. Men and women in rural areas desire more children than those in urban areas. This study was aimed at describing and comparing the factors that influence family size decisions among men and women in Bokkos, a rural Local Government Area in Plateau state, Nigeria. A cross sectional descriptive comparative study was used. Data was collected using structured interviewer administered questionnaires. Seventy two percent of women and 83.6% of men who desire to have 1-4 children had at least a secondary school education. Close to seventy percent of both men and women would have fewer children if they are certain of their survival to adulthood. Over 50% of the respondents believe that the husbands should have the final say on family size decisions. Preference for male children influences decisions on family size among men and women in the study population.

  17. Neurons and astroglia govern microglial endotoxin tolerance through macrophage colony-stimulating factor receptor-mediated ERK1/2 signals.

    PubMed

    Chu, Chun-Hsien; Wang, Shijun; Li, Chia-Ling; Chen, Shih-Heng; Hu, Chih-Fen; Chung, Yi-Lun; Chen, Shiou-Lan; Wang, Qingshan; Lu, Ru-Band; Gao, Hui-Ming; Hong, Jau-Shyong

    2016-07-01

    Endotoxin tolerance (ET) is a reduced responsiveness of innate immune cells like macrophages/monocytes to an endotoxin challenge following a previous encounter with the endotoxin. Although ET in peripheral systems has been well studied, little is known about ET in the brain. The present study showed that brain immune cells, microglia, being different from peripheral macrophages, displayed non-cell autonomous mechanisms in ET formation. Specifically, neurons and astroglia were indispensable for microglial ET. Macrophage colony-stimulating factor (M-CSF) secreted from these non-immune cells was essential for governing microglial ET. Neutralization of M-CSF deprived the neuron-glia conditioned medium of its ability to enable microglia to form ET when microglia encountered two lipopolysaccharide (LPS) treatments. Recombinant M-CSF protein rendered enriched microglia refractory to the second LPS challenge leading to microglial ET. Activation of microglial M-CSF receptor (M-CSFR; also known as CSF1R) and the downstream ERK1/2 signals was responsible for M-CSF-mediated microglial ET. Endotoxin-tolerant microglia in neuron-glia cultures displayed M2-like polarized phenotypes, as shown by upregulation of M2 marker Arg-1, elevated production of anti-inflammatory cytokine interleukin 10, and decreased secretion of pro-inflammatory mediators (tumor necrosis factor α, nitric oxide, prostaglandin E2 and interleukin 1β). Endotoxin-tolerant microglia protected neurons against LPS-elicited inflammatory insults, as shown by reduced neuronal damages in LPS pre-treatment group compared with the group without LPS pre-treatment. Moreover, while neurons and astroglia became injured during chronic neuroinflammation, microglia failed to form ET. Thus, this study identified a distinct non-cell autonomous mechanism of microglial ET. Interactions of M-CSF secreted by neurons and astroglia with microglial M-CSFR programed microglial ET. Loss of microglial ET could be an important

  18. Simulation of soil loss processes based on rainfall runoff and the time factor of governance in the Jialing River Watershed, China.

    PubMed

    Wu, Lei; Long, Tian-Yu; Liu, Xia; Mmereki, Daniel

    2012-06-01

    Jialing River is the largest tributary in the catchment area of Three Gorges Reservoir, and it is also one of the important areas of sediment yield in the upper reaches of the Yangtze River. In recent years, significant changes of water and sediment characteristics have taken place. The "Long Control" Project implemented since 1989 had greatly changed the surface appearance of the Jialing River Watershed (JRW), and it had made the environments of the watershed sediment yield and sediment transport change significantly. In this research, the Revised Universal Soil Loss Equation was selected and used to predict the annual average amount of soil erosion for the special water and sediment environments in the JRW after the implementation of the "Long Control" Project, and then the rainfall-runoff modulus and the time factor of governance were both considered as dynamic factors, the dynamic sediment transport model was built for soil erosion monitoring and forecasting based on the average sediment yield model. According to the dynamic model, the spatial and temporal distribution of soil erosion amount and sediment transport amount of the JRW from 1990 to 2007 was simulated using geographic information system (GIS) technology and space-grid algorithm. Simulation results showed that the average relative error of sediment transport was less than 10% except for the extreme hydrological year. The relationship between water and sediment from 1990 to 2007 showed that sediment interception effects of the soil and water conservation projects were obvious: the annual average sediment discharge reduced from 145.3 to 35 million tons, the decrement of sediment amount was about 111 million tons, and decreasing amplitude was 76%; the sediment concentration was also decreased from 2.01 to 0.578 kg/m(3). These data are of great significance for the prediction and estimation of the future changing trends of sediment storage in the Three Gorges Reservoir and the particulate non

  19. Ybp1 and Gpx3 Signaling in Candida albicans Govern Hydrogen Peroxide-Induced Oxidation of the Cap1 Transcription Factor and Macrophage Escape

    PubMed Central

    Patterson, Miranda J.; McKenzie, Christopher G.; Smith, Deborah A.; da Silva Dantas, Alessandra; Sherston, Sam; Veal, Elizabeth A.; Morgan, Brian A.; MacCallum, Donna M.

    2013-01-01

    Abstract Aims: As Candida albicans is the major fungal pathogen of humans, there is an urgent need to understand how this pathogen evades toxic reactive oxygen species (ROS) generated by the host immune system. A key regulator of antioxidant gene expression, and thus ROS resistance, in C. albicans is the AP-1-like transcription factor Cap1. Despite this, little is known regarding the intracellular signaling mechanisms that underlie the oxidation and activation of Cap1. Therefore, the aims of this study were; (i) to identify the regulatory proteins that govern Cap1 oxidation, and (ii) to investigate the importance of Cap1 oxidation in C. albicans pathogenesis. Results: In response to hydrogen peroxide (H2O2), but not glutathione-depleting/modifying oxidants, Cap1 oxidation, nuclear accumulation, phosphorylation, and Cap1-dependent gene expression, is mediated by a glutathione peroxidase-like enzyme, which we name Gpx3, and an orthologue of the Saccharomyces cerevisiae Yap1 binding protein, Ybp1. In addition, Ybp1 also functions to stabilise Cap1 and this novel function is conserved in S. cerevisiae. C. albicans cells lacking Cap1, Ybp1, or Gpx3, are unable to filament and thus, escape from murine macrophages after phagocytosis, and also display defective virulence in the Galleria mellonella infection model. Innovation: Ybp1 is required to promote the stability of fungal AP-1-like transcription factors, and Ybp1 and Gpx3 mediated Cap1-dependent oxidative stress responses are essential for the effective killing of macrophages by C. albicans. Conclusion: Activation of Cap1, specifically by H2O2, is a prerequisite for the subsequent filamentation and escape of this fungal pathogen from the macrophage. Antioxid. Redox Signal. 19, 2244–2260. PMID:23706023

  20. Neurons and astroglia govern microglial endotoxin tolerance through macrophage colony-stimulating factor receptor-mediated ERK1/2 signals

    PubMed Central

    Chu, Chun-Hsien; Wang, Shijun; Li, Chia-Ling; Chen, Shih-Heng; Hu, Chih-Fen; Chung, Yi-Lun; Chen, Shiou-Lan; Wang, Qingshan; Lu, Ru-Band; Gao, Hui-Ming; Hong, Jau-Shyong

    2016-01-01

    Endotoxin tolerance (ET) is a reduced responsiveness of innate immune cells like macrophages/monocytes to an endotoxin challenge following a previous encounter with the endotoxin. Although ET in peripheral systems has been well studied, little is known about ET in the brain. The present study showed that brain immune cells, microglia, being different from peripheral macrophages, displayed non-cell autonomous mechanisms in ET formation. Specifically, neurons and astroglia were indispensable for microglial ET. Macrophage colony-stimulating factor (M-CSF) secreted from these non-immune cells was essential for governing microglial ET. Neutralization of M-CSF deprived the neuron-glia conditioned medium of its ability to enable microglia to form ET when microglia encountered two lipopolysaccharide (LPS) treatments. Recombinant M-CSF protein rendered enriched microglia refractory to the second LPS challenge leading to microglial ET. Activation of microglial M-CSF receptor (M-CSFR; also known as CSF1R) and the downstream ERK1/2 signals was responsible for M-CSF-mediated microglial ET. Endotoxin-tolerant microglia in neuron-glia cultures displayed M2-like polarized phenotypes, as shown by upregulation of M2 marker Arg-1, elevated production of anti-inflammatory cytokine interleukin 10, and decreased secretion of pro-inflammatory mediators (tumor necrosis factor α, nitric oxide, prostaglandin E2 and interleukin 1β). Endotoxin-tolerant microglia protected neurons against LPS-elicited inflammatory insults, as shown by reduced neuronal damages in LPS pre-treatment group compared with the group without LPS pre-treatment. Moreover, while neurons and astroglia became injured during chronic neuroinflammation, microglia failed to form ET. Thus, this study identified a distinct non-cell autonomous mechanism of microglial ET. Interactions of M-CSF secreted by neurons and astroglia with microglial M-CSFR programed microglial ET. Loss of microglial ET could be an important

  1. Neurons and astroglia govern microglial endotoxin tolerance through macrophage colony-stimulating factor receptor-mediated ERK1/2 signals.

    PubMed

    Chu, Chun-Hsien; Wang, Shijun; Li, Chia-Ling; Chen, Shih-Heng; Hu, Chih-Fen; Chung, Yi-Lun; Chen, Shiou-Lan; Wang, Qingshan; Lu, Ru-Band; Gao, Hui-Ming; Hong, Jau-Shyong

    2016-07-01

    Endotoxin tolerance (ET) is a reduced responsiveness of innate immune cells like macrophages/monocytes to an endotoxin challenge following a previous encounter with the endotoxin. Although ET in peripheral systems has been well studied, little is known about ET in the brain. The present study showed that brain immune cells, microglia, being different from peripheral macrophages, displayed non-cell autonomous mechanisms in ET formation. Specifically, neurons and astroglia were indispensable for microglial ET. Macrophage colony-stimulating factor (M-CSF) secreted from these non-immune cells was essential for governing microglial ET. Neutralization of M-CSF deprived the neuron-glia conditioned medium of its ability to enable microglia to form ET when microglia encountered two lipopolysaccharide (LPS) treatments. Recombinant M-CSF protein rendered enriched microglia refractory to the second LPS challenge leading to microglial ET. Activation of microglial M-CSF receptor (M-CSFR; also known as CSF1R) and the downstream ERK1/2 signals was responsible for M-CSF-mediated microglial ET. Endotoxin-tolerant microglia in neuron-glia cultures displayed M2-like polarized phenotypes, as shown by upregulation of M2 marker Arg-1, elevated production of anti-inflammatory cytokine interleukin 10, and decreased secretion of pro-inflammatory mediators (tumor necrosis factor α, nitric oxide, prostaglandin E2 and interleukin 1β). Endotoxin-tolerant microglia protected neurons against LPS-elicited inflammatory insults, as shown by reduced neuronal damages in LPS pre-treatment group compared with the group without LPS pre-treatment. Moreover, while neurons and astroglia became injured during chronic neuroinflammation, microglia failed to form ET. Thus, this study identified a distinct non-cell autonomous mechanism of microglial ET. Interactions of M-CSF secreted by neurons and astroglia with microglial M-CSFR programed microglial ET. Loss of microglial ET could be an important

  2. KAP Surveys and Dengue Control in Colombia: Disentangling the Effect of Sociodemographic Factors Using Multiple Correspondence Analysis

    PubMed Central

    Quintero, Juliana

    2016-01-01

    During the last few decades, several studies have analyzed and described knowledge, attitudes, and practices (KAP) of populations regarding dengue. However, few studies have applied geometric data analytic techniques to generate indices from KAP domains. Results of such analyses have not been used to determine the potential effects of sociodemographic variables on the levels of KAP. The objective was to determine the sociodemographic factors related to different levels of KAP regarding dengue in two hyper-endemic cities of Colombia, using a multiple correspondence analysis (MCA) technique. In the context of a cluster randomized trial, 3,998 households were surveyed in Arauca and Armenia between 2012 and 2013. To generate KAP indexes, we performed a MCA followed by a hierarchical cluster analysis to classify each score in different groups. A quantile regression for each of the score groups was conducted. KAP indexes explained 56.1%, 79.7%, and 83.2% of the variance, with means of 4.2, 1.4, and 3.2 and values that ranged from 1 to 7, 7 and 11, respectively. The highest values of the index denoted higher levels of knowledge and practices. The attitudes index did not show the same relationship and was excluded from the analysis. In the quantile regression, age (0.06; IC: 0.03, 0.09), years of education (0.14; IC: 0.06, 0.22), and history of dengue in the family (0.21; IC: 0.12, 0.31) were positively related to lower levels of knowledge regarding dengue. The effect of such factors gradually decreased or disappeared when knowledge was higher. The practices indexes did not evidence a correlation with sociodemographic variables. These results suggest that the transformation of categorical variables into a single index by the use of MCA is possible when analyzing knowledge and practices regarding dengue from KAP questionnaires. Additionally, the magnitude of the effect of socioeconomic variables on the knowledge scores varies according to the levels of knowledge, suggesting

  3. Hepatitis B virus infection status is an independent risk factor for multiple myeloma patients after autologous hematopoietic stem cell transplantation.

    PubMed

    Li, Juan; Liu, Junru; Huang, Beihui; Zheng, Dong; Chen, Mei; Zhou, Zhenhai; Xu, Duorong; Zou, Waiyi

    2013-06-01

    The purposes of this study were to evaluate the infection by hepatitis B virus (HBV) and its impact on survival and to provide a clinical reference for monitoring and treating HBV during and after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A retrospective analysis of HBV infections was performed in 70 MM patients who received a sequential bortezomib-containing induction therapy and ASCT in our department from June 2006 to February 2012. Among the 70 patients in our study, 11 cases (15.7 %) were hepatitis B surface antigen positive (HBsAg+), and 23 cases (33.3 %) were hepatitis B core antibody positive (HBcAb+). Eight cases were HBsAg, hepatitis B e antibody (HBeAb), and HBcAb positive, while one case was HBsAg, hepatitis B e antigen (HBeAg), and HBcAb positive. The median follow-up times for the HBsAg+ group and the HBsAg-negative (HBsAg-) group were 27.0 (7.6-85.2) months and 28.7 (7.1-111.0) months, respectively. The 1-year, 2-year, and 3-year overall survival rates of the HBsAg+ group were 90.9, 80.8, and 34.6 %, respectively, and the median survival time was 31.2 months (95 % CI, 24.8-37.6). The 1-year, 2-year, and 3-year overall survival rates of the HBsAg- group were 98.2, 94, and 84.6 %, respectively, while the median survival time was not yet available. There was a statistically significant difference (p=0.008) in the overall survival rate between the two groups. By Cox regression analysis, we found that the HBsAg+ status was a prognostic factor, which could independently influence the overall survival rate for ASCT. In conclusion, the HBsAg+ status is an independent risk factor for patients with MM receiving ASCT. The application of standard antiviral treatment might help to overcome this risk factor. PMID:23436046

  4. Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus.

    PubMed

    He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

    2016-01-01

    WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions

  5. Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus.

    PubMed

    He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

    2016-01-01

    WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions

  6. Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus

    PubMed Central

    He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

    2016-01-01

    WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions

  7. Health governance: principal-agent linkages and health system strengthening.

    PubMed

    Brinkerhoff, Derick W; Bossert, Thomas J

    2014-09-01

    Governance is increasingly recognized as an important factor in health system performance, yet conceptually and practically it remains poorly understood and subject to often vague and competing notions of both what its role is and how to address its weaknesses. This overview article for the symposium on health governance presents a model of health governance that focuses on the multiplicity of societal actors in health systems, the distribution of roles and responsibilities among them and their ability and willingness to fulfil these roles and responsibilities. This focus highlights the principal-agent linkages among actors and the resulting incentives for good governance and health system performance. The discussion identifies three disconnects that constitute challenges for health system strengthening interventions that target improving governance: (1) the gap between the good governance agenda and existing capacities, (2) the discrepancy between formal and informal governance and (3) the inattention to sociopolitical power dynamics. The article summarizes the three country cases in the symposium and highlights their governance findings: health sector reform in China, financial management of health resources in Brazilian municipalities and budget reform in hospitals in Lesotho. The concluding sections clarify how the three cases apply the model's principal-agent linkages and highlight the importance of filling the gaps remaining between problem diagnosis and the development of practical guidance that supports 'best fit' solutions and accommodates political realities in health systems strengthening.

  8. Treatment Results of Postoperative Radiotherapy on Squamous Cell Carcinoma of the Oral Cavity: Coexistence of Multiple Minor Risk Factors Results in Higher Recurrence Rates

    SciTech Connect

    Fan, Kang-Hsing; Wang, Hung-Ming; Kang, Chung-Jan

    2010-07-15

    Purpose: The aim of this study was to investigate the treatment results of postoperative radiotherapy (PORT) on squamous cell carcinoma of the oral cavity (OSCC). Materials and Methods: This study included 302 OSCC patients who were treated by radical surgery and PORT. Indications for PORT include Stage III or IV OSCC according to the 2002 criteria of the American Joint Committee on Cancer, the presence of perineural invasion or lymphatic invasion, the depth of tumor invasion, or a close surgical margin. Patients with major risk factors, such as multiple nodal metastases, a positive surgical margin, or extracapsular spreading, were excluded. The prescribed dose of PORT ranged from 59.4 to 66.6Gy (median, 63Gy). Results: The 3-year overall and recurrence-free survival rates were 73% and 70%, respectively. Univariate analysis revealed that differentiation, perineural invasion, lymphatic invasion, bone invasion, location (hard palate and retromolar trigone), invasion depths {>=}10mm, and margin distances {<=}4mm were significant prognostic factors. The presence of multiple significant factors of univariate analysis correlated with disease recurrence. The 3-year recurrence-free survival rates were 82%, 76%, and 45% for patients with no risk factors, one or two risk factors, and three or more risk factors, respectively. After multivariate analysis, the number of risk factors and lymphatic invasion were significant prognostic factors. Conclusion: PORT may be an adequate adjuvant therapy for OSCC patients with one or two risk factors of recurrence. The presence of multiple risk factors and lymphatic invasion correlated with poor prognosis, and more aggressive treatment may need to be considered.

  9. Phosphorylation and Dephosphorylation of the Presequence of Precursor MULTIPLE ORGANELLAR RNA EDITING FACTOR3 during Import into Mitochondria from Arabidopsis.

    PubMed

    Law, Yee-Song; Zhang, Renshan; Guan, Xiaoqian; Cheng, Shifeng; Sun, Feng; Duncan, Owen; Murcha, Monika W; Whelan, James; Lim, Boon Leong

    2015-10-01

    The nucleus-encoded mitochondria-targeted proteins, multiple organellar RNA editing factors (MORF3, MORF5, and MORF6), interact with Arabidopsis (Arabidopsis thaliana) PURPLE ACID PHOSPHATASE2 (AtPAP2) located on the chloroplast and mitochondrial outer membranes in a presequence-dependent manner. Phosphorylation of the presequence of the precursor MORF3 (pMORF3) by endogenous kinases in wheat germ translation lysate, leaf extracts, or STY kinases, but not in rabbit reticulocyte translation lysate, resulted in the inhibition of protein import into mitochondria. This inhibition of import could be overcome by altering threonine/serine residues to alanine on the presequence, thus preventing phosphorylation. Phosphorylated pMORF3, but not the phosphorylation-deficient pMORF3, can form a complex with 14-3-3 proteins and HEAT SHOCK PROTEIN70. The phosphorylation-deficient mutant of pMORF3 also displayed faster rates of import when translated in wheat germ lysates. Mitochondria isolated from plants with altered amounts of AtPAP2 displayed altered protein import kinetics. The import rate of pMORF3 synthesized in wheat germ translation lysate into pap2 mitochondria was slower than that into wild-type mitochondria, and this rate disparity was not seen for pMORF3 synthesized in rabbit reticulocyte translation lysate, the latter translation lysate largely deficient in kinase activity. Taken together, these results support a role for the phosphorylation and dephosphorylation of pMORF3 during the import into plant mitochondria. These results suggest that kinases, possibly STY kinases, and AtPAP2 are involved in the import of protein into both mitochondria and chloroplasts and provide a mechanism by which the import of proteins into both organelles may be coordinated.

  10. A High-Throughput Photodynamic Therapy Screening Platform with On-Chip Control of Multiple Microenvironmental Factors

    PubMed Central

    Lou, Xia; Kim, Gwangseong; Yoon, Hyung Ki; Lee, Yong-Eun Koo; Kopelman, Raoul

    2014-01-01

    We present a novel high-throughput microfluidic platform that enables the evaluation of the anticancer efficacy of photodynamic therapy (PDT) drugs over multiple microenvironmental factors. PDT is uniquely complex, originating from its dependence on three separate but essential elements: drug (or also called photosensitizer), oxygen, and light. Thus, obtaining a reliable evaluation of PDT efficacy is highly challenging, requiring considerable effort and time to evaluate all three interdependent parameters. In this paper, we report a high-throughput efficacy screening platform that we implemented by developing microfluidic components that individually control basic PDT elements (photosensitizer concentrations, oxygen levels, and light fluence), and then integrating them into a single triple-layer device. The integrated microfluidic chip consists of an array of small compartment, each corresponding to a specific combination of these three variables. This allows for more than 1,000 different conditions being tested in parallel. Cancer cells are cultured within the device, exposed to different PDT conditions, and then monitored for their viability using live/dead fluorescence staining. The entire screening assay takes only 1 hour, and the collected PDT outcomes (cell viability) for combinatorial screening are analysed and reported as traditional dose-response curves or 3D bubble charts using a custom software. As a proof of concept, methylene blue is adopted as a photosensitizer and its drug efficacy on C6 glioma cells has been successfully evaluated for total 324 PDT conditions using the fabricated chip. This platform can facilitate not only the development of new photosensitizers but also the optimization of current PDT protocols. PMID:24394779

  11. Global Effect of Indole-3-Acetic Acid Biosynthesis on Multiple Virulence Factors of Erwinia chrysanthemi 3937▿

    PubMed Central

    Yang, Shihui; Zhang, Qiu; Guo, Jianhua; Charkowski, Amy O.; Glick, Bernard R.; Ibekwe, A. Mark; Cooksey, Donald A.; Yang, Ching-Hong

    2007-01-01

    Production of the plant hormone indole-3-acetic acid (IAA) is widespread among plant-associated microorganisms. The non-gall-forming phytopathogen Erwinia chrysanthemi 3937 (strain Ech3937) possesses iaaM (ASAP16562) and iaaH (ASAP16563) gene homologues. In this work, the null knockout iaaM mutant strain Ech138 was constructed. The IAA production by Ech138 was reduced in M9 minimal medium supplemented with l-tryptophan. Compared with wild-type Ech3937, Ech138 exhibited reduced ability to produce local maceration, but its multiplication in Saintpaulia ionantha was unaffected. The pectate lyase production of Ech138 was diminished. Compared with wild-type Ech3937, the expression levels of an oligogalacturonate lyase gene, ogl, and three endopectate lyase genes, pelD, pelI, and pelL, were reduced in Ech138 as determined by a green fluorescent protein-based fluorescence-activated cell sorting promoter activity assay. In addition, the transcription of type III secretion system (T3SS) genes, dspE (a putative T3SS effector) and hrpN (T3SS harpin), was found to be diminished in the iaaM mutant Ech138. Compared with Ech3937, reduced expression of hrpL (a T3SS alternative sigma factor) and gacA but increased expression of rsmA in Ech138 was also observed, suggesting that the regulation of T3SS and pectate lyase genes by IAA biosynthesis might be partially due to the posttranscriptional regulation of the Gac-Rsm regulatory pathway. PMID:17189441

  12. Phosphorylation and Dephosphorylation of the Presequence of Precursor MULTIPLE ORGANELLAR RNA EDITING FACTOR3 during Import into Mitochondria from Arabidopsis.

    PubMed

    Law, Yee-Song; Zhang, Renshan; Guan, Xiaoqian; Cheng, Shifeng; Sun, Feng; Duncan, Owen; Murcha, Monika W; Whelan, James; Lim, Boon Leong

    2015-10-01

    The nucleus-encoded mitochondria-targeted proteins, multiple organellar RNA editing factors (MORF3, MORF5, and MORF6), interact with Arabidopsis (Arabidopsis thaliana) PURPLE ACID PHOSPHATASE2 (AtPAP2) located on the chloroplast and mitochondrial outer membranes in a presequence-dependent manner. Phosphorylation of the presequence of the precursor MORF3 (pMORF3) by endogenous kinases in wheat germ translation lysate, leaf extracts, or STY kinases, but not in rabbit reticulocyte translation lysate, resulted in the inhibition of protein import into mitochondria. This inhibition of import could be overcome by altering threonine/serine residues to alanine on the presequence, thus preventing phosphorylation. Phosphorylated pMORF3, but not the phosphorylation-deficient pMORF3, can form a complex with 14-3-3 proteins and HEAT SHOCK PROTEIN70. The phosphorylation-deficient mutant of pMORF3 also displayed faster rates of import when translated in wheat germ lysates. Mitochondria isolated from plants with altered amounts of AtPAP2 displayed altered protein import kinetics. The import rate of pMORF3 synthesized in wheat germ translation lysate into pap2 mitochondria was slower than that into wild-type mitochondria, and this rate disparity was not seen for pMORF3 synthesized in rabbit reticulocyte translation lysate, the latter translation lysate largely deficient in kinase activity. Taken together, these results support a role for the phosphorylation and dephosphorylation of pMORF3 during the import into plant mitochondria. These results suggest that kinases, possibly STY kinases, and AtPAP2 are involved in the import of protein into both mitochondria and chloroplasts and provide a mechanism by which the import of proteins into both organelles may be coordinated. PMID:26304849

  13. Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain following neuronal activation.

    PubMed Central

    Metsis, M; Timmusk, T; Arenas, E; Persson, H

    1993-01-01

    The rat brain-derived neurotropic factor (BDNF) gene consists of four 5' exons linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. To gain insights into the regulation of BDNF mRNA expression, probes specific for the different 5' exons were used to study the expression of BDNF mRNA in the brain. Following a systemic injection of the glutamate analog kainic acid, exon I, II, and III mRNAs increased transiently in hippocampus and cerebral cortex. A modest increase was seen for exon IV, where a new transcription initiation site was induced by this treatment. Pretreatments with the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3-dihydroxy-6-nitrosulfanoylbenzo(f)quinoxaline revealed two region-specific patterns of glutamate receptor-mediated regulation. The first pattern found in neocortex, piriform cortex, and amygdala involves regulation of BDNF exon I, II, and III mRNAs through NMDA and AMPA/kainate receptors. The second pattern found in the hippocampus involves regulation of BDNF exon I, II, and III mRNAs by high-affinity kainate or metabotropic receptors. Treatment with the gamma-aminobutyric acid subtype A (GABAA) receptor antagonist bicuculline increased exon I and III mRNAs in the denate gyrus, and the muscarinic receptor agonist pilocarpine increased exon I mRNA mainly in the neocortex. These data show that the four BDNF promoters allow multiple points of BDNF mRNA regulation and suggest that the activation of different subtypes of glutamate receptors differentially regulates the expression of BDNF exon-specific mRNAs in the brain. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8415610

  14. Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis

    PubMed Central

    Naghashpour, Mahshid; Amani, Reza; Sarkaki, Alireza; Ghadiri, Ata; Samarbafzadeh, Alireza; Jafarirad, Sima; Malehi, Amal Saki

    2016-01-01

    Objective(s): In the present study, C57BL/6 female mice (n=56) were used to explore the neuroprotective effects of riboflavin in motor disability of experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis. Materials and Methods: The animals were assigned into 7 groups: sham-operated 1 (SO1), healthy mice receiving PBS (phosphate buffer saline); sham-operated 2 (SO2), healthy mice receiving PBS and riboflavin; sham treatment 1 (ST1), EAE mice receiving water; sham treatment 2 (ST2), EAE mice receiving sodium acetate buffer; treatment 1 (T1), EAE mice receiving interferon beta-1a (INFβ-1a); treatment 2 (T2), EAE mice receiving riboflavin; treatment 3 (T3), EAE mice receiving INFβ-1a and riboflavin. After EAE induction, scoring was performed based on clinical signs. Upon detecting score 0.5, riboflavin at 10 mg/kg of body weight and/or INFβ-1a at 150 IU/g of body weight administration was started for two weeks. The brain and spinal cord levels of brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-17A (IL-17A) were studied using real-time PCR and ELISA methods. Results: BDNF expression and protein levels were increased in the brain and spinal cord of the T3 group compared with the other groups (P<0.01). IL-6 and IL-17A expressions were increased in the brains of the T3 and T1 groups, respectively, compared to the other groups (P<0.01). The daily clinical score was reduced significantly by riboflavin in both effector and chronic phases of the disease compared with that of the controls (P<0.05). Conclusion: Our findings showed that riboflavin is capable of suppressing the neurological disability mediated by BDNF and IL-6. PMID:27279989

  15. The Drosophila Transcription Factor Dimmed Affects Neuronal Growth and Differentiation in Multiple Ways Depending on Neuron Type and Developmental Stage

    PubMed Central

    Liu, Yiting; Luo, Jiangnan; Nässel, Dick R.

    2016-01-01

    Growth of postmitotic neurons occurs during different stages of development, including metamorphosis, and may also be part of neuronal plasticity and regeneration. Recently we showed that growth of post-mitotic neuroendocrine cells expressing the basic helix loop helix (bHLH) transcription factor Dimmed (Dimm) in Drosophila could be regulated by insulin/IGF signaling and the insulin receptor (dInR). Dimm is also known to confer a secretory phenotype to neuroendocrine cells and can be part of a combinatorial code specifying terminal differentiation in peptidergic neurons. To further understand the mechanisms of Dimm function we ectopically expressed Dimm or Dimm together with dInR in a wide range of Dimm positive and Dimm negative peptidergic neurons, sensory neurons, interneurons, motor neurons, and gut endocrine cells. We provide further evidence that dInR mediated cell growth occurs in a Dimm dependent manner and that one source of insulin-like peptide (DILP) for dInR mediated cell growth in the CNS is DILP6 from glial cells. Expressing both Dimm and dInR in Dimm negative neurons induced growth of cell bodies, whereas dInR alone did not. We also found that Dimm alone can regulate cell growth depending on specific cell type. This may be explained by the finding that the dInR is a direct target of Dimm. Conditional gene targeting experiments showed that Dimm alone could affect cell growth in certain neuron types during metamorphosis or in the adult stage. Another important finding was that ectopic Dimm inhibits apoptosis of several types of neurons normally destined for programmed cell death (PCD). Taken together our results suggest that Dimm plays multiple transcriptional roles at different developmental stages in a cell type-specific manner. In some cell types ectopic Dimm may act together with resident combinatorial code transcription factors and affect terminal differentiation, as well as act in transcriptional networks that participate in long term maintenance

  16. Hand washing behavior and associated factors in Vietnam based on the Multiple Indicator Cluster Survey, 2010–2011

    PubMed Central

    To, Kien Gia; Lee, Jong-Koo; Nam, You-Seon; Trinh, Oanh Thi Hoang; Van Do, Dung

    2016-01-01

    Background Handwashing is a cost-effective way of preventing communicable diseases such as respiratory and food-borne illnesses. However, handwashing rates are low in developing countries. Target 7C of the seventh Millennium Development Goals was to increase by half the proportion of people with sustainable access to safe drinking water and basic sanitation by 2015. Studies have found that better access to improved water sources and sanitation is associated with higher rates of handwashing. Objective Our goal was to describe handwashing behaviour and identify the associated factors in Vietnamese households. Design Data from 12,000 households participating in the Vietnam Multiple Indicator Cluster Survey 2011 were used. The survey used a multistage sampling method to randomly select 100 clusters and 20 households per cluster. Self-administered questionnaires were used to collect data from a household representative. Demographic variables, the presence of a specific place for handwashing, soap and water, access to improved sanitation, and access to improved water sources were tested for association with handwashing behaviour in logistic regression. Results Almost 98% of households had a specific place for handwashing, and 85% had cleansing materials and water at such a place. The prevalence of handwashing in the sample was almost 85%. Educational level, ethnicity of the household head, and household wealth were factors associated with handwashing practice (p<0.05). Those having access to an improved sanitation facility were more likely to practise handwashing [odds ratio (OR)=1.69, 95% confidence interval (CI): 1.37–2.09, p<0.001], as were those with access to improved water sources (OR=1.74, 95% CI: 1.37–2.21, p<0.001). Conclusions Households with low education, low wealth, belonging to ethnic minorities, and with low access to improved sanitation facilities and water sources should be targeted for interventions implementing handwashing practice. In addition

  17. Total joint replacement: A multiple risk factor analysis of physical activity level 1–2 years postoperatively

    PubMed Central

    Torres, Andy; Love, Rebecca M; Barber, Thomas C; Sheth, Dhiren S; Inacio, Maria C S

    2016-01-01

    Background and purpose — The effect of total joint arthroplasty (TJA) on physical activity is not fully understood. We investigated the change in physical activity after TJA and patient factors associated with change. Patients and methods — Using a total joint replacement registry, primary total hip arthroplasty (THA) patients (n = 5,678) and knee arthroplasty (TKA) patients (n = 11,084) between January 1, 2010 and December 31, 2012 were identified. Median age at THA was 68 and median age at TKA was 67. Change in self-reported physical activity (minutes per week) from before TJA (within 1 year of surgery) to after TJA (1–2 years) was the outcome of interest. Patient demographics and comorbidities were evaluated as risk factors. Multiple linear regression was used. Results — Median physical activity before surgery was 50 min/week (IQR: 0–140) for THA patients and 58 (IQR: 3–143) for TKA patients. Median physical activity after surgery was 150 min/week (IQR: 60–280) for both THA patients and TKA patients. Following TJA, 50% of patients met CDC/WHO physical activity guideline criteria. Higher body mass index was associated with lower change in physical activity (THA: −7.1 min/week; TKA: −5.9 min/week). Females had lower change than males (THA: −11 min/week; TKA: −9.1 min/week). In TKA patients, renal failure was associated with lower change (−17 min/week), as were neurological disorders (−30 min/week). Interpretation — Self-reported minutes of physical activity increased from before to after TJA, but 50% of TJA patients did not meet recommended physical activity guideline criteria. Higher body mass index, female sex, and specific comorbidities were found to be associated with low change in physical activity. Patient education on the benefits of physical activity should concentrate on these subgroups of patients. PMID:27299567

  18. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

    PubMed Central

    Santo, Vítor E.; Mano, João F.; Reis, Rui L.

    2013-01-01

    The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

  19. Impact of multiple cardiovascular risk factors on femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa Heart Study).

    PubMed

    Paul, Timir K; Srinivasan, Sathanur R; Chen, Wei; Li, Shengxu; Bond, M Gene; Tang, Rong; Berenson, Gerald S

    2005-02-15

    Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification.

  20. Important factors governing exposure of the population and countermeasure application in rural settlements of the Russian Federation in the long-term after the Chernobyl accident.

    PubMed

    Fesenko, S; Jacob, P; Alexakhin, R; Sanzharova, N I; Panov, A; Fesenko, G; Cecille, L

    2001-01-01

    Rural settlements located in areas of the Russian Federation contaminated after the Chernobyl accident and exceeding an annual dose of 1 mSv a-1 have been classified according to 137Cs contamination density, internal dose and the neighbourhood of forests. It has been shown that, with the exception of the most contaminated areas, the internal doses decreased in accordance with a decline in 137Cs availability for plant root uptake. An inverse tendency was observed in areas with 137Cs contamination above 555 kBq m-2 which can be explained by a reduction or even termination of countermeasure application and by an increasing consumption of forest products in areas where restrictive countermeasures are still implemented. Twenty-seven settlements have been studied to estimate the effectiveness of countermeasures applied previously and to identify the most important factors governing the radiation exposure to the population and its change with time. It has been shown that the effectiveness of countermeasures which resulted in a decrease of up to 40% of doses has a tendency to decline in the long term. The need for continuation of remediation in rural settlements was evaluated both for selected settlements and extrapolated to the whole contaminated area and it has been shown that the application of countermeasures will be of importance at least up to the year 2045. Rather high effectiveness in terms of internal dose reduction (factor of 2-2.5) of radical improvement (disking, ploughing and reseeding) and administration of Cs binders to animals (Ferrocyn) was demonstrated for the selected settlements. It could be demonstrated that for forest-remote settlements there is a linear dependence between internal dose normalised to the density of contamination and the proportion of peat soils around settlements. For near-forest settlements, this dependence was less pronounced which can be explained by the high contribution of forest food products to the internal dose. Milk is still

  1. Genetic association studies of tumour necrosis factor alpha and beta and tumour necrosis factor receptor 1 and 2 polymorphisms across the clinical spectrum of multiple sclerosis.

    PubMed

    McDonnell, G V; Kirk, C W; Middleton, D; Droogan, A G; Hawkins, S A; Patterson, C C; Graham, C A

    1999-11-01

    Allelic association studies with microsatellite markers around the tumour-necrosis factor (TNF) genes have demonstrated significantly different allele distributions of TNF markers (a and b) between relapsing-remitting/secondary progressive multiple sclerosis (MS) (RR/SPMS) patients and normal controls. Considering the suspected genetic and immunological heterogeneity in MS, we tested this association in primary progressive MS (PPMS) patients. Elevated levels of serum soluble TNF receptors (sTNF-R) are reported in patients with gadolinium enhancing lesions, and animal models suggest a possible therapeutic role of sTNF-RI in MS. Thus we performed similar association studies using markers for the TNF-R genes. Gene association studies were carried out on 199-216 normal controls, 174 RR/SPMS patients and 102 PPMS patients using polymorphic dinucleotide repeat TNF markers (a, b and d), and separate markers for TNF-RI and TNF-RII. Forward primers were fluorescently labelled, polymerase chain reaction (PCR) products were analysed on a fluorescent fragment analyser, and Genescan 672 software was used for allele sizing. Samples were typed for HLA-DR antigens using PCR technology and sequence-specific oligonucleotide probes. TNFa marker allele distributions differed significantly between PPMS patients and controls (P = 0.028), largely attributable to an increase in the 118-bp TNFa allele in PPMS patients (P = 0.00024). Allele distributions were similar in PPMS and RR/SPMS patients (P = 0.91). Logistic regression analysis, however, indicated that these associations were not independent of that with HLA-DRB1*15. For the TNFb marker, the 127-bp allele showed association with both patient categories (PPMS vs. controls, P = 0.010; RR/SPMS vs. controls, P = 0.027), whilst the 128-bp allele occurred more frequently in controls (PPMS vs. controls, P = 0.036: RR/SPMS vs. controls, P = 0.0009). As with the TNFa 118 bp allele, the association with TNFb was not independent of the HLA

  2. Characterization of concentration, particle size distribution, and contributing factors to ambient hexavalent chromium in an area with multiple emission sources

    NASA Astrophysics Data System (ADS)

    Yu, Chang Ho; Huang, Lihui; Shin, Jin Young; Artigas, Francisco; Fan, Zhi-hua (Tina)

    2014-09-01

    Airborne hexavalent chromium (Cr(VI)) is a known pulmonary carcinogen and can be emitted from both natural and anthropogenic sources, including diesel emissions. However, there is limited knowledge about ambient Cr(VI) concentration levels and its particle size distribution. This pilot study characterized ambient Cr(VI) concentrations in the New Jersey Meadowlands (NJ ML) district, which is close to the heavily trafficked New Jersey Turnpike (NJTPK) as well as Chromium Ore Processing Residue (COPR) waste sites. Monitoring was simultaneously conducted at two sites, William site (∼50 m from NJTPK) and MERI site (∼700 m from NJTPK). The distance between the two sites is approximately 6.2 km. Ambient Cr(VI) concentrations and PM2.5 mass concentrations were concurrently measured at both sites during summer and winter. The summer concentrations (mean ± S.D. [median]), 0.13 ± 0.06 [0.12] ng/m3 at the MERI site and 0.08 ± 0.05 [0.07] ng/m3 at the William site, were all significantly higher than the winter concentrations, 0.02 ± 0.01 [0.02] ng/m3 and 0.03 ± 0.01 [0.03] ng/m3 at the MERI and William sites, respectively. The site difference (i.e., MERI > William) was observed for summer Cr(VI) concentrations; however, no differences for winter and pooled datasets. These results suggest higher Cr(VI) concentrations may be attributed from stronger atmospheric reactions such as photo-oxidation of Cr(III) to Cr(VI) in the summer. The Cr(VI) distribution as a function of particle size, ranging from 0.18 to 18 μm, was determined at the William site. It was found that Cr(VI) was enriched in the particles less than 2.5 μm in diameter (PM2.5). This finding suggested potential health concerns, because PM2.5 are easily inhaled and deposited in the alveoli. A multiple linear regression analysis confirmed ambient Cr(VI) concentrations were significantly affected by meteorological factors (i.e., temperature and humidity) and reactive gases/particles (i.e., O3, Fe and Mn).

  3. The role of the multiple banded antigen of Ureaplasma parvum in intra-amniotic infection: major virulence factor or decoy?

    PubMed

    Dando, Samantha J; Nitsos, Ilias; Kallapur, Suhas G; Newnham, John P; Polglase, Graeme R; Pillow, J Jane; Jobe, Alan H; Timms, Peter; Knox, Christine L

    2012-01-01

    The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×10⁴ CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32-170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a

  4. The Role of the Multiple Banded Antigen of Ureaplasma parvum in Intra-Amniotic Infection: Major Virulence Factor or Decoy?

    PubMed Central

    Dando, Samantha J.; Nitsos, Ilias; Kallapur, Suhas G.; Newnham, John P.; Polglase, Graeme R.; Pillow, J. Jane; Jobe, Alan H.; Timms, Peter; Knox, Christine L.

    2012-01-01

    The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×104 CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32–170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a

  5. Geomagnetic disturbances may be environmental risk factor for multiple sclerosis: an ecological study of 111 locations in 24 countries

    PubMed Central

    2012-01-01

    Background We noticed that a hypothesis based on the effect of geomagnetic disturbances (GMD) has the ability to explain special features of multiple sclerosis (MS). Areas around geomagnetic 60 degree latitude (GM60L) experience the greatest amount of GMD. The easiest way to evaluate our hypothesis was to test the association of MS prevalence (MSP) with angular distance to geomagnetic 60 degree latitude (AMAG60) and compare it with the known association of MS with geographical latitude (GL). We did the same with angular distance to geographic 60 degree latitude (AGRAPH60) as a control. Methods English written papers with MSP keywords, done in Europe (EUR), North America (NA) or Australasia (AUS) were retrieved from the PubMed. Geomagnetic coordinates were determined for each location and AMAG60 was calculated as absolute value of numerical difference between its geomagnetic latitude from GM60L. By an ecological study with using meta-regression analyses, the relationship of MSP with GL, AMAG60 and AGRAPH60 were evaluated separately. MSP data were weighted by square root of number of prevalent cases. Models were compared by their adjusted R square (AR2) and standard error of estimate (SEE). Results 111 MSP data were entered in the study. In each continent, AMAG60 had the best correlation with MSP, the largest AR2 (0.47, 0.42 and 0.84 for EUR, NA and AUS, respectively) and the least SEE. Merging both hemispheres data, AMAG60 explained 56% of MSP variations with the least SEE (R = 0.75, AR2 = 0.56, SEE = 57), while GL explained 17% (R = 0.41, AR2 = 0.17, SEE = 78.5) and AGRAPH60 explained 12% of that variations with the highest SEE (R = 0.35, AR2 = 0.12, SEE = 80.5). Conclusions Our results confirmed that AMAG60 is the best describer of MSP variations and has the strongest association with MSP distribution. They clarified that the well-known latitudinal gradient of MSP may be actually a gradient related to GM60L. Moreover, the

  6. The CCND1 870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma

    PubMed Central

    Chen, Bowang; Försti, Asta; Hosking, Fay J; Broderick, Peter; Ma, Yussanne P; Dobbins, Sara E; Hose, Dirk; Walker, Brian A; Davies, Faith E; Kaiser, Martin F; Li, Ni L; Gregory, Walter A; Jackson, Graham H; Witzens-Harig, Mathias; Neben, Kai; Hoffmann, Per; Nöthen, Markus M; Mühleisen, Thomas W; Eisele, Lewin; Ross, Fiona M; Jauch, Anna; Goldschmidt, Hartmut; Houlston, Richard S; Morgan, Gareth J; Hemminki, Kari

    2016-01-01

    A number of specific chromosomal abnormalities define the subgroups of multiple myeloma. In a meta-analysis of two genomewide association studies of multiple myeloma totaling 1,661 patients we investigated risk for developing a specific tumor karyotype. The t(11;14) (q13;q32) translocation in which CCDN1 is placed under the control of the immunoglobin heavy chain enhancer was strongly associated with the CCDN1 870G>A polymorphism (P =7.96 x10-11). These results provide for a model in which a constitutional genetic factor is associated with risk of a specific chromosomal translocation. PMID:23502783

  7. Evaluation in the Government Marketplace.

    ERIC Educational Resources Information Center

    House, Ernest R.

    1997-01-01

    The large government market in evaluation that has developed in recent years does not follow the idealized image of open markets because of the contracting process, which means that a few firms conduct most evaluations. To produce honest, unbiased evaluations, evaluation ethics must take government market factors into consideration. (SLD)

  8. Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish.

    PubMed

    Pelster, Bernd; Egg, Margit

    2015-01-01

    In zebrafish, as in most vertebrates, three different isoforms of the hypoxia-inducible transcription factor, Hif-1α, Hif-2α, and Hif-3α, have been identified. The expression data of genes encoding these three proteins, as analyzed so far, show distinct expression patterns for all three isoforms during early development, under hypoxic conditions, and during exercise, suggesting differential roles for all three proteins under these different conditions. While isoform-specific functions for Hif-1α and Hif-2α have been identified in recent years, the role of Hif-3α remains somewhat elusive. Several studies mostly using mammalian cells or tissues discussed Hif-3α as a competitive inhibitor of Hif-1α and Hif-2α. In zebrafish, the expression changes for Hif-1α and Hif-3α observed during development and under environmental stress conditions do not support this hypothesis, and recent studies indicate that Hif-3α is also able to directly control transcriptional activity of certain genes. The Hif signaling pathway is tightly connected to cell circuitries such as glucose and lipid metabolism, and only very recently a further linkage to the circadian clock has been described. In this context a detailed analysis of the mRNA concentrations of hif-1α, hif-2α, and hif-3α also revealed a circadian expression pattern for hif-3α mRNA under normoxic conditions in zebrafish larvae. In addition, accumulation of Hif-1α protein during short-term hypoxia was found to depend on the time within the daily light and dark cycle at which hypoxia was encountered, suggesting that the hypoxia signaling pathway may be regulated by the circadian clock. This is supported by the fact that some of the downstream genes of the Hif signaling pathway, namely, erythropoietin and vascular endothelial growth factor, are known to be clock controlled as well. Furthermore, in developing zebrafish, the disruption of the circadian rhythm was shown to result in a diminished hypoxic response with a

  9. Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats.

    PubMed

    Lai, Lina; Chen, Yunxia; Tian, Xiaoxia; Li, Xujiong; Zhang, Xiaojing; Lei, Jingwen; Bi, Yanghui; Fang, Buwu; Song, Xiaoliang

    2015-10-15

    The current study was performed in order to explore the effect of artesunate (Art) on experimental hepatic fibrosis and the potential mechanism involved. Art, a water-soluble hemisuccinate derivative of artemisinin extracted from the Chinese herb Artemisia Annua, is a safe and effective antimalarial drug. Hepatic fibrosis was induced in SD rats by multiple pathogenic factors. Rats were treated concurrently with Art (28.8 mg/kg) given daily by oral gavage for 6 or 8 weeks to evaluate its protective effects. Our data demonstrated that Art treatment obviously attenuated hepatic fibrosis, characterized by less inflammatory infiltration and accumulation of extracellular matrix (ECM). Art remarkably decreased endotoxin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels as well. Art significantly downregulated protein and mRNA expression of α-smooth muscle actin (α-SMA), toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88) and transforming growth factor beta 1 (TGF-β1). Art also significantly inhibited the nuclear transcription factor kappa B p65 (NF-κB p65) translocation into the nucleus. In addition, there were no remarkable differences between the N group and the NA group. In conclusion, we found that Art could alleviate hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats, suggesting that Art may be a potential candidate for the therapy of hepatic fibrosis. PMID:26318197

  10. Predicting Prostate Cancer Mortality Among Men With Intermediate to High-Risk Disease and Multiple Unfavorable Risk Factors

    SciTech Connect

    Nguyen, Paul L. Chen Minghui; Catalona, William J.; Moul, Judd W.; Sun, Leon; D'Amico, Anthony V.

    2009-03-01

    Purpose: To determine whether the number of unfavorable risk factors could be used to predict the risk of prostate cancer-specific mortality (PCSM) among men with intermediate- to high-risk prostate cancer. Methods and Materials: We studied 1,063 men who underwent radical prostatectomy (n = 559), external beam radiotherapy (n = 288), or radiotherapy plus androgen suppression therapy (n = 116) for prostate cancer between 1965 and 2002. Fine and Gray's regression analysis was used to determine whether an increasing number of unfavorable risk factors (prostate-specific antigen level >10 ng/mL, Gleason score of {>=}7, clinical Stage T2b or greater, or pretreatment prostate-specific antigen velocity >2.0 ng/mL/y) was associated with the interval to PCSM and all-cause mortality. Results: Median follow-up was 5.6 years. Compared with those with one risk factor, the adjusted hazard ratio for PCSM was 2.3 (95% confidence interval 1.1-4.8; p = 0.03) for two risk factors, 5.4 (95% confidence interval 2.7-10.7; p < 0.0001) for three risk factors, and 13.6 (95% confidence interval 6.3-29.2; p < 0.0001) for all four risk factors. The 5-year cumulative incidence of PCSM was 2.4% for one factor, 2.4% for two factors, 7.0% for three factors, and 14.7% for all four factors. Prostate cancer deaths as a proportion of all deaths was 19% for one factor, 33% for two factors, 53% for three factors, and 80% for four factors. Conclusion: The number of unfavorable risk factors was significantly associated with PCSM. Prostate cancer was the major cause of death in men with at least three risk factors. Therefore, these men should be considered for clinical trials designed to assess whether survival is prolonged with the addition of novel agents to current standards of practice.

  11. Stationary spiraling eddies in presence of polar amplification of global warming as a governing factor of ecology of Greenland seals White Sea population: results of verification study

    NASA Astrophysics Data System (ADS)

    Melentyev, K.; Chernook, V.; Melentyev, V.

    2003-04-01

    Ice-associated forms of marine mammals are representatives of a high level of fodder chains in the ocean and taxation of population number for different group, as assessment of ecology and animal welfare are the important tasks for marine biology, ecology, fishery and other application uses. Many problems create a global warming and antropogenical impact on marine and coastal ecosystem. In order to investigate ice covered Arctic Ocean and charting the number of seals were performed annual inspections onboard research aircraft PINRO "Arktika". Multi-spectral airborne and satellite observations were fulfilled regularly from Barents and White Sea to the Bering and Okhotsk Sea (1996-2002). A contemporary status of different group of sea mammals was evaluated, where number of adults and pups were checked separately. In situ observations were provided with using helicopter and icebreaker for gathering a water samples and ice cores (with following biochemical and toxicological analysis). A prevailing part of life cycle of Greenland seals (harp seal) is strongly depended from winter hydrology (water masses, stable currents, meandering fronts, stationary eddies) and closely connected with type of ice (pack, fast ice) and other parameters of ice (age, origin, salinity, ice edge.). First-year ice floes which has a specific properties and distinctive features are used by harp seals for pupping, lactation, molting, pairing and resting. Ringed seals, inversely, use for corresponding purposes only fast-ice. Different aspects of ecology, and migration features of harp seals were analyzed in frame of verification study. It was revealed a scale of influence of winter severity and wind regime, but stationary eddies in the White Sea is most effective governing factor (novelty). Following relationship " eddies - ecology of Greenland seal White Sea population " will be discussed: A) regularities of eddies formation and their spatial arrangement, temporal (seasonal and annual

  12. Identification of the factors that govern the ability of therapeutic antibodies to provide postchallenge protection against botulinum toxin: a model for assessing postchallenge efficacy of medical countermeasures against agents of bioterrorism and biological warfare.

    PubMed

    Al-Saleem, Fetweh H; Nasser, Zidoon; Olson, Rebecca M; Cao, Linsen; Simpson, Lance L

    2011-08-01

    Therapeutic antibodies are one of the major classes of medical countermeasures that can provide protection against potential bioweapons such as botulinum toxin. Although a broad array of antibodies are being evaluated for their ability to neutralize the toxin, there is little information that defines the circumstances under which these antibodies can be used. In the present study, an effort was made to quantify the temporal factors that govern therapeutic antibody use in a postchallenge scenario. Experiments were done involving inhalation administration of toxin to mice, intravenous administration to mice, and direct application to murine phrenic nerve-hemidiaphragm preparations. As part of this study, several pharmacokinetic characteristics of botulinum toxin and neutralizing antibodies were measured. The core observation that emerged from the work was that the window of opportunity within which postchallenge administration of antibodies exerted a beneficial effect increased as the challenge dose of toxin decreased. The critical factor in establishing the window of opportunity was the amount of time needed for fractional redistribution of a neuroparalytic quantum of toxin from the extraneuronal space to the intraneuronal space. This redistribution event was a dose-dependent phenomenon. It is likely that the approach used to identify the factors that govern postchallenge efficacy of antibodies against botulinum toxin can be used to assess the factors that govern postchallenge efficacy of medical countermeasures against any agent of bioterrorism or biological warfare.

  13. Governance matters: an ecological association between governance and child mortality

    PubMed Central

    Lin, Ro-Ting; Chien, Lung-Chang; Chen, Ya-Mei; Chan, Chang-Chuan

    2014-01-01

    Background Governance of a country may have widespread effects on the health of its population, yet little is known about the effect of governance on child mortality in a country that is undergoing urbanization, economic development, and disease control. Methods We obtained indicators of six dimensions of governance (perceptions of voice and accountability, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and control of corruption) and national under-5 mortality rates for 149 countries between 1996 and 2010. We applied a semi-parametric generalized additive mixed model to examine associations after controlling for the effects of development factors (urbanization level and economy), disease control factors (hygienic conditions and vaccination rates), health expenditures, air quality, and time. Results Governance, development, and disease control showed clear inverse relations with the under-5 mortality rate (p<0.001). Per unit increases in governance, development, and disease control factors, the child mortality rate had a 0.901-, 0.823-, and 0.922-fold decrease, respectively, at fixed levels of the other two factors. Conclusions In the effort to reduce the global under-5 mortality rate, addressing a country's need for better governance is as important as improvements in development and disease control. PMID:24711600

  14. Is Tobacco Use Associated with Academic Failure among Government School Students in Urban India?

    ERIC Educational Resources Information Center

    Dhavan, Poonam; Stigler, Melissa H.; Perry, Cheryl L.; Arora, Monika; Reddy, K. Srinath

    2010-01-01

    Background: Not much is known about the academic correlates of tobacco use among students in developing countries. This study investigated associations between multiple forms of tobacco use, psychosocial risk factors, and academic failure among 10- to 16-year-old government school students in Delhi and Chennai, India. Methods: This study was a…

  15. Effect of treatment with a colloidal oatmeal lotion on the acneform eruption induced by epidermal growth factor receptor and multiple tyrosine-kinase inhibitors.

    PubMed

    Alexandrescu, D T; Vaillant, J G; Dasanu, C A

    2007-01-01

    Current treatment modalities for epidermal growth factor (EGFR)-positive cancers have recently included the use of antibodies and small-molecule tyrosine-kinase inhibitors (TKI). A significant limiting step in the use of these agents is dermatological toxicity, frequently in the form of an acneiform eruption. Present management modalities for this toxicity are largely ineffective. Colloidal oatmeal lotion demonstrates multiple anti-inflammatory properties with known effects on arachidonic acid, cytosolic phospholipase A2 and tumour necrosis factor-alpha pathways, along with an excellent side-effect profile. Treatment with colloidal oatmeal was applied to 11 patients with a rash induced by cetuximab, erlotinib, panitumumab and sorafenib. Of the 10 assessable patients, 6 had complete response and 4 partial response, giving a response rate of 100% with no associated toxicities. Treatment with colloidal oatmeal lotion is efficient in controlling the rash associated with EGFR and multiple TKI, and allows continuation of the antineoplastic treatment.

  16. Risk factors for development of multiple-class resistance to Streptococcus pneumoniae Strains in Belgium over a 10-year period: antimicrobial consumption, population density, and geographic location.

    PubMed

    Van Eldere, Johan; Mera, Robertino M; Miller, Linda A; Poupard, James A; Amrine-Madsen, Heather

    2007-10-01

    We investigated the impact of the usage of antibiotics in ambulatory patients in Belgium in 147 defined geographical circumscriptions and at the individual isolate level. The study included 14,448 Streptococcus pneumoniae strains collected by the Belgium national reference lab from 1994 to 2004. Additional risk factors for resistance, such as population density/structure and day care attendance, were investigated for the same time-space window. A statistical model that included resistance to two or more antimicrobial classes offered the best fit for measuring the changes in nonsusceptibility to penicillin, macrolides, and tetracycline over time and place in Belgium. Analysis at the geographic level identified antimicrobial consumption with a 1-year lag (0.5% increase per additional defined daily dose) and population density as independent predictors of multiple resistance. Independent risk factors at the isolate level were age (odds ratio [OR], 1.55 for children aged <5 years), population density (7% increase in multiple resistance per 100 inhabitants/km(2)), conjugate 7-valent vaccine serotype (OR, 14.3), location (OR, 1.55 for regions bordering high-resistance France), and isolate source (OR, 1.54 for ear isolates). The expansion of multiple-resistant strains explains most of the overall twofold increase and subsequent decrease in single antimicrobial resistance between 1994 and 2004. We conclude that factors in addition to antibiotic use, such as high population density and proximity to high-resistance regions, favor multiple resistance. Regional resistance rates are not linearly related to actual antibiotic use but are linked to past antibiotic use plus a combination of demographic and geographic factors.

  17. A registry-based case-control study of risk factors for the development of multiple non-fatal injuries on the job.

    PubMed

    Li, C Y; Du, C L; Chen, C J; Sung, F C

    1999-07-01

    Using compensation records of Taiwan, we conducted a case-control study nested within a cohort of 77,846 active workers who experienced at least one incidence of non-fatal work-related injury between 1994 and 1996 in order to explore factors associated with risk of sustaining multiple non-fatal injuries in the workplace. Cases (n = 2,616) were workers with more than three incidences of non-fatal injury during the study period and controls (n = 3,974) were randomly sampled from workers who experienced only one incidence of non-fatal injury during the same period. Compared with construction workers, workers employed in mining and quarrying (OR = 2.7), manufacturing (OR = 1.2), commerce (OR = 1.6), transport, storage and communication (OR = 1.3) and social, personal and community service (OR = 1.4) were all at significantly elevated risk of multiple non-fatal injuries. Both age and wage showed a significant dose-response effect on the risk of developing multiple non-fatal injuries. The preliminary analysis suggests that workers in certain industries are at significantly elevated risks of multiple work-related non-fatal injuries, in particular those in the mining and quarry industries. Additionally, further preventive measures should be aimed at protecting older workers from such injuries and further studies would help provide more specific interpretations on the positive association between higher wage earning and risk of multiple non-fatal injuries. PMID:10628060

  18. A registry-based case-control study of risk factors for the development of multiple non-fatal injuries on the job.

    PubMed

    Li, C Y; Du, C L; Chen, C J; Sung, F C

    1999-07-01

    Using compensation records of Taiwan, we conducted a case-control study nested within a cohort of 77,846 active workers who experienced at least one incidence of non-fatal work-related injury between 1994 and 1996 in order to explore factors associated with risk of sustaining multiple non-fatal injuries in the workplace. Cases (n = 2,616) were workers with more than three incidences of non-fatal injury during the study period and controls (n = 3,974) were randomly sampled from workers who experienced only one incidence of non-fatal injury during the same period. Compared with construction workers, workers employed in mining and quarrying (OR = 2.7), manufacturing (OR = 1.2), commerce (OR = 1.6), transport, storage and communication (OR = 1.3) and social, personal and community service (OR = 1.4) were all at significantly elevated risk of multiple non-fatal injuries. Both age and wage showed a significant dose-response effect on the risk of developing multiple non-fatal injuries. The preliminary analysis suggests that workers in certain industries are at significantly elevated risks of multiple work-related non-fatal injuries, in particular those in the mining and quarry industries. Additionally, further preventive measures should be aimed at protecting older workers from such injuries and further studies would help provide more specific interpretations on the positive association between higher wage earning and risk of multiple non-fatal injuries.

  19. Patterns of evolution at the gametophytic self-incompatibility Sorbus aucuparia (Pyrinae) S pollen genes support the non-self recognition by multiple factors model

    PubMed Central

    Aguiar, Bruno; Vieira, Jorge; Cunha, Ana E.; Fonseca, Nuno A.; Reboiro-Jato, David; Reboiro-Jato, Miguel; Fdez-Riverola, Florentino; Raspé, Olivier; Vieira, Cristina P.

    2013-01-01

    S-RNase-based gametophytic self-incompatibility evolved once before the split of the Asteridae and Rosidae. In Prunus (tribe Amygdaloideae of Rosaceae), the self-incompatibility S-pollen is a single F-box gene that presents the expected evolutionary signatures. In Malus and Pyrus (subtribe Pyrinae of Rosaceae), however, clusters of F-box genes (called SFBBs) have been described that are expressed in pollen only and are linked to the S-RNase gene. Although polymorphic, SFBB genes present levels of diversity lower than those of the S-RNase gene. They have been suggested as putative S-pollen genes, in a system of non-self recognition by multiple factors. Subsets of allelic products of the different SFBB genes interact with non-self S-RNases, marking them for degradation, and allowing compatible pollinations. This study performed a detailed characterization of SFBB genes in Sorbus aucuparia (Pyrinae) to address three predictions of the non-self recognition by multiple factors model. As predicted, the number of SFBB genes was large to account for the many S-RNase specificities. Secondly, like the S-RNase gene, the SFBB genes were old. Thirdly, amino acids under positive selection—those that could be involved in specificity determination—were identified when intra-haplotype SFBB genes were analysed using codon models. Overall, the findings reported here support the non-self recognition by multiple factors model. PMID:23606363

  20. Predicting probability of occurrence and factors affecting distribution and abundance of three Ozark endemic crayfish species at multiple spatial scales

    USGS Publications Warehouse

    Nolen, Matthew S.; Magoulick, Daniel D.; DiStefano, Robert J.; Imhoff, Emily M.; Wagner, Brian K.

    2014-01-01

    We found that a range of environmental variables were important in predicting crayfish distribution and abundance at multiple spatial scales and their importance was species-, response variable- and scale dependent. We would encourage others to examine the influence of spatial scale on species distribution and abundance patterns.

  1. The Relationship of Selected Supply- and Demand-Side Factors to Forms of Perceived Discrimination among Adults with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Roessler, Richard T.; Neath, Jeanne; McMahon, Brian T.; Rumrill, Phillip D.

    2007-01-01

    Single-predictor and stepwise multinomial logistic regression analyses and an external validation were completed on 3,082 allegations of employment discrimination by adults with multiple sclerosis. Women filed two thirds of the allegations, and individuals between 31 and 50 made the vast majority of discrimination charges (73%). Allegations…

  2. Multiple versus Single Maintaining Factors of Challenging Behaviours as Assessed by the QABF for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Boisjoli, Jessica A.

    2007-01-01

    Background: The "Questions About Behavioral Function" (QABF) correctly identifies maintaining variables of challenging behaviour. However, for adults who have a long history of challenging behaviours, identifying one clear function of the maladaptive behaviour is difficult. Additionally, the person may develop multiple functions of their…

  3. Multiple-Component Remediation for Developmental Reading Disabilities: IQ, Socioeconomic Status, and Race as Factors in Remedial Outcome

    ERIC Educational Resources Information Center

    Morris, Robin D.; Lovett, Maureen W.; Wolf, Maryanne; Sevcik, Rose A.; Steinbach, Karen A.; Frijters, Jan C.; Shapiro, Marla B.

    2012-01-01

    Results from a controlled evaluation of remedial reading interventions are reported: 279 young disabled readers were randomly assigned to a program according to a 2 x 2 x 2 factorial design (IQ, socioeconomic status [SES], and race). The effectiveness of two multiple-component intervention programs for children with reading disabilities (PHAB +…

  4. Patterns of Service Use, Individual and Contextual Risk Factors, and Resilience among Adolescents Using Multiple Psychosocial Services

    ERIC Educational Resources Information Center

    Ungar, Michael; Liebenberg, Linda; Dudding, Peter; Armstrong, Mary; van de Vijver, Fons J. R.

    2013-01-01

    Background: Very little research has examined the relationship between resilience, risk, and the service use patterns of adolescents with complex needs who use multiple formal and mandated services such as child welfare, mental health, juvenile justice, and special educational supports. This article reports on a study of 497 adolescents in…

  5. Examining the Factor Structure and Psychometric Properties of the Quality of Life Scale among People with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Fitzgerald, Shawn M.; Li, Jian; Rumrill, Phillip D., Jr.; Bishop, Malachy; Merchant, William R.

    2015-01-01

    Rehabilitation counseling researchers seeking to more fully understand the phenomenon of psychosocial adaptation to disability are devoting increased attention to the impact of disability on quality of life (QOL). This impact has been of particular interest among multiple sclerosis (MS) researchers. The complex etiology, unpredictable nature, and…

  6. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    PubMed Central

    Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

    2013-01-01

    Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF), and bone morphogenetic protein 7 (BMP7) were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure. PMID:23293519

  7. The design, implementation and acceptability of an integrated intervention to address multiple behavioral and psychosocial risk factors among pregnant African American women

    PubMed Central

    Katz, Kathy S; Blake, Susan M; Milligan, Renee A; Sharps, Phyllis W; White, Davene B; Rodan, Margaret F; Rossi, Maryann; Murray, Kennan B

    2008-01-01

    Background African American women are at increased risk for poor pregnancy outcomes compared to other racial-ethnic groups. Single or multiple psychosocial and behavioral factors may contribute to this risk. Most interventions focus on singular risks. This paper describes the design, implementation, challenges faced, and acceptability of a behavioral counseling intervention for low income, pregnant African American women which integrated multiple targeted risks into a multi-component format. Methods Six academic institutions in Washington, DC collaborated in the development of a community-wide, primary care research study, DC-HOPE, to improve pregnancy outcomes. Cigarette smoking, environmental tobacco smoke exposure, depression and intimate partner violence were the four risks targeted because of their adverse impact on pregnancy. Evidence-based models for addressing each risk were adapted and integrated into a multiple risk behavior intervention format. Pregnant women attending six urban prenatal clinics were screened for eligibility and risks and randomized to intervention or usual care. The 10-session intervention was delivered in conjunction with prenatal and postpartum care visits. Descriptive statistics on risk factor distributions, intervention attendance and length (i.e., with < 4 sessions considered minimal adherence) for all enrolled women (n = 1,044), and perceptions of study participation from a sub-sample of those enrolled (n = 152) are reported. Results Forty-eight percent of women screened were eligible based on presence of targeted risks, 76% of those eligible were enrolled, and 79% of those enrolled were retained postpartum. Most women reported a single risk factor (61%); 39% had multiple risks. Eighty-four percent of intervention women attended at least one session (60% attended ≥ 4 sessions) without disruption of clinic scheduling. Specific risk factor content was delivered as prescribed in 80% or more of the sessions; 78% of sessions were

  8. Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues

    PubMed Central

    Hisamatsu, Daisuke; Ohno-Oishi, Michiko; Nakamura, Shiho; Mabuchi, Yo; Naka-Kaneda, Hayato

    2016-01-01

    The senescence-associated secretory phenotype (SASP) has attracted attention as a mechanism that connects cellular senescence to tissue dysfunction, and specific SASP factors have been identified as systemic pro-aging factors. However, little is known about the age-dependent changes in the secretory properties of stem cells. Young, but not old, mesenchymal stem/stromal cells (MSCs) are a well-known source of critical regenerative factors, but the identity of these factors remains elusive. In this study, we identified growth differentiation factor 6 (Gdf6; also known as Bmp13 and CDMP-2) as a regenerative factor secreted from young MSCs. The expression of specific secretory factors, including Gdf6, was regulated by the microRNA (miRNA) miR-17, whose expression declined with age. Upregulation of Gdf6 restored the osteogenic capacity of old MSCs in vitro and exerted positive effects in vivo on aging-associated pathologies such as reduced lymphopoiesis, insufficient muscle repair, reduced numbers of neural progenitors in the brain, and chronic inflammation. Our results suggest that manipulation of miRNA could enable control of the SASP, and that regenerative factors derived from certain types of young cells could be used to treat geriatric diseases. PMID:27311402

  9. Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and. alpha. 1-antitrypsin genes

    SciTech Connect

    Costa, R.H. ); Grayson, D.R. ); Darnell, J.E. Jr. )

    1989-04-01

    Transthyretin (TTR) and {alpha}1-antitrypsin ({alpha}1-AT) are expressed at high levels in the liver and also in at least one other cell type. The authors report here a detailed analysis of the proximal regulatory region of the TTR gene, which has uncovered two new DNA-binding factors that are present mainly (or only) in hepatocytes. One of these new factors, hepatocyte nuclear factor 3 (HNF-3), binds to two sites that are crucial in TTR expression as well as to two additional sites in the {alpha}1-AT proximal enhancer region. The second new factor, HNF-4, binds to two sites in TTR that are required for gene activity. The authors had previously identified binding sites for another hepatocyte-enriched DNA-binding protein (C/EBP or a relative thereof), and additional promoter-proximal sites for that protein in both TTR and {alpha}1-AT are also reported here. From these results it seems clear that cell-specific expression is not simply the result of a single cell-specific factor for each gene but the results of a combination of such factors. The variation and distribution of such factors among different cell types could be an important basis for the coordinate expression of the TTR and {alpha}1-AT genes in the liver or the discordant transcriptional activation of these genes in a few other cell types. The identification of such cell-enriched factors is a necessary prelude to understanding the basis for cell specificity.

  10. Short communication: comparison of virulence factors in Klebsiella pneumoniae strains associated with multiple or single cases of mastitis.

    PubMed

    Kanevsky-Mullarky, I; Nedrow, A J; Garst, S; Wark, W; Dickenson, M; Petersson-Wolfe, C S; Zadoks, R N

    2014-01-01

    Klebsiella pneumoniae mastitis in dairy cattle is generally due to an opportunistic infection from the environment, resulting in large heterogeneity among mastitis-causing strains within a herd. However, in mastitis outbreaks in 4 herds, several strains of K. pneumoniae were identified as the cause of infection in multiple cows, suggesting increased ability to either cause disease or evade host defenses. In this study, differences in capsule formation and immune evasion were compared in 5 pairs of K. pneumoniae strains, where one strain in each pair was associated with multiple cases of mastitis and the other with a single case of mastitis. Production of capsular polysaccharide, ability to evade killing by polymorphonuclear neutrophilic leukocytes (PMNL), and the relationship between the 2 were evaluated for each strain grown in broth or milk. Growth of isolates in skim milk increased capsule size and ability to evade killing by PMNL, depending on strain type. Specifically, strains associated with multiple cases of mastitis had increased capsule size in skim milk. Strains associated with single cases of mastitis were better able to evade killing by PMNL when grown in skim milk. Our results, although preliminary, suggest that the 2 groups of strains may constitute different subpopulations of K. pneumoniae. However, our findings do not indicate that capsule or evasions of killing by PMNL explain increased mastitis outbreaks with Klebsiella. Further work will explain the enhanced ability of some strains to cause mastitis in dairy cows.

  11. Short communication: comparison of virulence factors in Klebsiella pneumoniae strains associated with multiple or single cases of mastitis.

    PubMed

    Kanevsky-Mullarky, I; Nedrow, A J; Garst, S; Wark, W; Dickenson, M; Petersson-Wolfe, C S; Zadoks, R N

    2014-01-01

    Klebsiella pneumoniae mastitis in dairy cattle is generally due to an opportunistic infection from the environment, resulting in large heterogeneity among mastitis-causing strains within a herd. However, in mastitis outbreaks in 4 herds, several strains of K. pneumoniae were identified as the cause of infection in multiple cows, suggesting increased ability to either cause disease or evade host defenses. In this study, differences in capsule formation and immune evasion were compared in 5 pairs of K. pneumoniae strains, where one strain in each pair was associated with multiple cases of mastitis and the other with a single case of mastitis. Production of capsular polysaccharide, ability to evade killing by polymorphonuclear neutrophilic leukocytes (PMNL), and the relationship between the 2 were evaluated for each strain grown in broth or milk. Growth of isolates in skim milk increased capsule size and ability to evade killing by PMNL, depending on strain type. Specifically, strains associated with multiple cases of mastitis had increased capsule size in skim milk. Strains associated with single cases of mastitis were better able to evade killing by PMNL when grown in skim milk. Our results, although preliminary, suggest that the 2 groups of strains may constitute different subpopulations of K. pneumoniae. However, our findings do not indicate that capsule or evasions of killing by PMNL explain increased mastitis outbreaks with Klebsiella. Further work will explain the enhanced ability of some strains to cause mastitis in dairy cows. PMID:24534505

  12. Event-related potentials to tones show differences between children with multiple risk factors for dyslexia and control children before the onset of formal reading instruction.

    PubMed

    Hämäläinen, Jarmo A; Lohvansuu, Kaisa; Ervast, Leena; Leppänen, Paavo H T

    2015-02-01

    Multiple risk factors can affect the development of specific reading problems or dyslexia. In addition to the most prevalent and studied risk factor, phonological processing, auditory discrimination problems have also been found in children and adults with reading difficulties. The present study examined 37 children between the ages of 5 and 6, 11 of which had multiple risk factors for developing reading problems. The children participated in a passive oddball EEG experiment with sinusoidal sounds with changes in sound frequency, duration, or intensity. The responses to the standard stimuli showed a negative voltage shift in children at risk for reading problems compared to control children at 107-215 ms in frontocentral areas corresponding to P1 offset and N250 onset. Source analyses showed that the difference originated from the left and right auditory cortices. Additionally, the children at risk for reading problems had a larger late discriminative negativity (LDN) response in amplitude for sound frequency change than the control children. The amplitudes at the P1-N250 time window showed correlations to letter knowledge and phonological identification whereas the amplitudes at the LDN time window correlated with verbal short-term memory and rapid naming. These results support the view that problems in basic auditory processing abilities precede the onset of reading instruction and can act as one of the risk factors for dyslexia.